Carbohydrate Chemistry v.21-Part I

Carbohydrate Chemistry Volume 21 Part I

A Specialist Periodical Report

Carbohydrate Chemistry Volume 21 Part I Monosaccharides, Disaccharides, and Specific Oligosaccharides A Review of the Recent Literature Published during 1987 Senior Reporter N. R. Williams, Birkbeck College, University of London Reporters B. E. Davison, Polytechnic of North London R. J. Ferrier, Victoria University of Wellington, New Zealand R. H. Furneaux, D.S.I.R., Petone, New Zealand P. C. Tyler, D.S.I.R., Petone, New Zealand R. H. Wightman, Heriot- Watt University, Edinburgh

SOCIETY OF HEMISTRY

ISBN 0-851 86-232-2 ISSN 0951-8428 @ The Royal Society of Chemistry, 1989

All Rights Reserved. No part of this book may be reproduced or transmitted in any form or by any means-graphic, electronic, including photocopying, recording, taping, or information storage and retrieval systems-without written permission from the Royal Society of Chemistry Published by the Royal Society of Chemistry Thomas Graham House, Cambridge CB4 4WF Printed in Great Britain by Whitstable Litho Printers Ltd., Whitstable, Kent

Preface

This report summarizes the literature for 1987 available to us by March 1988. The format of recent volumes has been retained. I regret that an unusual combination of factors has led to the exceptional delay in bringing this volume to publication. We are well aware that the value of this report diminishes with time, and since this is the last report for which I will be responsible as Senior Reporter, I hope Professor Ferrier will have more success in expediting publication as he takes over.

I would like to thank all my colleagues for their contributions to this volume. We welcome Dr. Peter Tyler as a new member of the team, bringing an even stronger New Zealand flavour to the I would also like to thank Dr. P.G. Gardam and Mr A.G. work. Cubitt and their colleagues at the Royal Society of Chemistry for the production of this report from our submitted typescripts.

Neil R. Williams July 1989

R E P R I N T S In response to several queries, the situation regarding reprints of chapters of Specialist Periodical Reports titles is that they are not made available because even a relatively small consequent decrease in sales would have a disproportionately large adverse effect on the precarious finances of this specialist series of books.

Conten& Chapter

1

Introduction and General Aspects

1

References Chapter

Chapter

Chapter

2

Free Sugars

2

1

Theoretical Aspects

2

2

Synthesis

3

3

Physical Measurements

7

4

Oxidation

9

5

Other Reactions

10

References

11

3

Glycosides and Disaccharides

14

1

0-Glycosides Synthesis of Monosaccharide Glycosides Synthesis of Disaccharides and their Derivatives 0-Glycosides Isolated from Natural Products Hydrolysis and Other Reactions and Features

14 14 20 24 25

2

S-Glycosides

26

3

C-Glycosides Pyranoid Compounds Furanoid Compounds

27 27

33

References

36

4

Oligosaccharides

41

1

General

41

2

Trisaccharides Linear Homotrisaccharides Linear Heterotrisaccharides Branched Heterotrisaccharides

41 41 42 43

3

Tetrasaccharides Linear Tetrasaccharides Rrwnched Tetrasaccharides

43 43 44

...

Carbohydrate Chemistry

Vlll

Chapter

4

Pentasaccharides

44

5

Hexasaccharides

45

6

Higher Saccharides

45

References

45

5

Ethers and Anhydro-sugars

48

1

Ethers Methyl Ethers Other Alkyl and Aryl Ethers Silyl Ethers

48

Intramolecular Ethers (Anhydro-sugars) Oxirans Other Anhydrides

51 51 52

References

55

6

Acetals

57

1

Isopropylidene Acetals

57

2

Benzylidene Acetals

58

3

Other Acetals

59

References

60

7

Esters

61

1

General Methods

61

2

Carboxylic Esters

62

3

Phosphate and Related Esters

67

4

Sulphonate Esters and Derivatives

69

5

Other Esters

70

References

72

8

Halogeno-sugars

75

1

Fluoro-sugars

75

2

Chloro-, Bromo-, and Iodo-sugars

78

References

80

2

Chapter

Chapter

Chapter

48 48

51

ix

Contents Chapter

Chapter

Chapter

Chapter

Chapter

Chapter

9

Amino-sugars

82

1

Natural Products

82

2

Synthesis

82

3

Reactions

91

4

Di- and Tri-amino-sugars

94

References

97

Miscellaneous Nitrogen Derivatives

100

1

Glycosylamines

100

2

Azido-sugars

104

3

Nitro- and Nitroso-sugars and Glycosyl Nitrones

105

4

Nitriles, Oximes, Hydroxylamines, and Imines

107

5

Hydrazones, Osazones, and Related Heterocycles

108

6

Other Heterocyclic Derivatives

109

References

110

Thio- and Seleno-sugars

112

References

117

Deoxy-sugars

119

References

125

Unsaturated Derivatives

127

1

Glycals

127

2

Other Unsaturated Derivatives

131

References

135

Branched-chain Sugars

137

1

Compounds with an R-C-0 Branch

137

2

Compounds with an R-C-N Branch

140

3

Compounds with an R-C-H, R-C-R, or C=R Branch

141

References

148

10

11

12

13

14

Carbohydrate Chemistry

X

Chapter

Chapter

Chapter

Chapter

Aldosuloses, Dialdoses, and Diuloses

150

1

Aldosuloses

150

2

Dialdoses

151

3

Diuloses

152

References

153

Sugar Acids and Lactones

154

1

General

154

2

Aldonic Acids

154

3

Saccharinic Acids

157

4

Ulosonic Acids

158

5

Uronic Acids

161

6

Ascorbic Acids

162

7

Aldaric Acids

164

References

165

Inorganic Derivatives

167

1

Carbon-bonded Phosphorus Derivatives

167

2

Other Carbon-bonded Derivatives

167

3

Oxygen-bonded Derivatives

168

References

170

Alditols and Cyclitols

172

1

Alditols Acyclic Alditols Anhydro-inositols Branched-chain Alditols Amino-alditols Heterocyclic Derivatives Miscellaneous Compounds

172 172 174 175 175 177 178

2

Cyclitols Inositols Amino-inositols Branched-chain Inositols Inositol Phosphates Miscellaneous Cyclitols

178 178 179 180 183 183

References

184

15

16

17

18

XI

Contents Chapter

Chapter

Chapter

Antibiotics

187

1

Amino-glycoside Antibiotics

187

2

Macrolide Antibiotics

189

3

Anthracycline and Related Polycyclic Antibiotics

190

4

Nucleoside Antibiotics

191

5

Glycopeptide Antibiotics

195

6

Miscellaneous Antibiotics

195

References

197

Nucleosides

201

1

Synthesis

201

2

Anhydro- and Cyclo-nucleosides

203

3

Deoxynucleosides

205

4

Halonucleosides

207

5

Amino- and Azido-nucleosides

208

6

Thionucleosides

209

7

Branched-chain Nucleosides

209

8

Nucleosides of Unsaturated Sugars, Keto-sugars, and Uronic Acids 210

9

C-Nucleosides

211

10

Carbocyclic Nucleoside Analogues

212

11

Nucleoside Phosphates and Phosphonates

214

12

Ethers of Nucleosides

216

13

Esters and Acetals of Nucleosides

216

14

Reactions

218

15

Spectroscopic and Conformational Studies

219

References

219

N.M.R. Spectroscopy and Conformational Features

225

1

Theoretical and General Considerationso

225

2

Acyclic Systems

226

3

Furanose Systems

226

19

20

21

Carbohydrate Chemistry

xii

Chapter

Chapter

Chapter

Pyranose Systems

227

Oligosaccharides and Related Compounds

229

N.M.R. of Nuclei other than '11

231

or 13C

References

231

Other Physical Methods

234

I.R. Spectroscopy

234

Mass Spectrometry

234

X-ray Crystallography

2 36

E.S.R. Spectroscopy

239

Polarimetry, Circular Dichroism, and Related Studies

239

References

240

Separatory and Analytical Methods

244

1

Chromatographic Methods General Gas-Liquid Chromatography Thin-layer Chromatography High-pressure Liquid Chromatography Column Chromatography

244 244 244 245 246 251

2

Electrophoresis

252

3

Other Analytical Methods

252

References

252

Synthesis of Enantiomerically Pure Noncarbohydrate Compounds

256

Carbocyclic Compounds

256

22

23

24

y-

Author Index

and &-Lactones

258

Macrolides and Their Constituent Segments

260

Sprioacetal Systems

262

Other Oxygen Heterocycles

264

Nitrogen Heterocycles

266

Acyclic Compounds

269

References

270 274

Abbreviations

The following abbreviations have been used: Ac Ad -qIBN A1 1 BBN Bn Boc Bz Cbz c.d. CI DAST DBU DCC DDQ DEAD D IBAL DMAP DMF DMSO EE e.s.r. FAB GC HMPT 1.r. LAH LDA LTBH MCPBA MEM MOM m.s. Ms NBS NIS n.m.r. 0.r.d. PCC PDC PTC PY SIMS TASF TBDMS Tf Tf a TFA THF ThP

acetyl adenin-9-yl 2,2'-azobisisobutyronitrile a1 lyl 9-borabicyclo [ 3 I 3 I 11 nonane benzyl t-butoxycarbonyl benzoyl benzyloxycarbonyl circular dichroism chemical ionization diethylaminosulphur trifluoride 1,5-diazabicyclo[5,4,0]undec-5-ene dicyclohexylcarbodi-imide 2,3-dichloro-5,6-dicyano-lI4-benzoquinone diethyl azodicarboxylate di-isobutylaluminium hydride 4-dimethylaminopyridine N,N-dimethylformamide dimethyl sulphoxide 1-ethoxyethyl electron spin resonance fast-atom bombardment gas chromatography hexamethylphosphorous triamide infrared lithium aluminium hydride lithium di-isopropylamide lithium triethylborohydride m-chloroperbenzoic acid methoxyethoxymethyl methoxymethyl mass spectrometry methanesulphonyl N-bromosuccinimide N-iodosuccinimide nuclear magnetic resonance optical rotatory dispersion pyridinium chlorochromate pyridinium dichromate phase transfer catalysis pyridine secondary-ion mass spectrometry tris(dimethy1amino)sulphonium difluorotrimethyl silicate t-butyldimethylsilyl trifluoromethanesulphonyl trifluoroacetyl trif luoroacetic acid tetrahydrofuran tetrahydropyranyl

...

XI11

Carbohydrate Chemistry

xiv TMS

TPP TPS

Tr Ts U

trimethylsilyl triphenylphosphine tri-isopropylbenzenesulphonyl triphenylmethyl toluene p-sulphonyl uracil-1-yl

1 Introduction and General Aspects

We hope that the following chapters provide a fair summary of the large amount of carbohydrate chemistry published in 1987, and give an indication of the wide range of compounds reported and studied during the year. The report covers monosaccharides, disaccharides, and specific oligosaccharides (as defined in Chapter 4 ) . As usual, the most extensive chapters cover glycosides and nucleosides, but several other chapters contain a large number of references, and over 1500 references altogether demonstrate the interest in this area of chemistry. The report reflects a particular surge of interest in C-glycosides in Chapter 3 and in inositol phosphates in Chapter 1 8 . The lack of a precise definition of a carbohydrate has led to somewhat arbitrary decisions as to whether border-line cases merit inclusion in our survey; we have tried to assess likely interest to carbohydrate chemists, or whether significant carbohydrate chemistry is discussed in work focussed as much if not more on aglycone units. We apologize if our judgement does not always meet with your approval. Reviews of a more general nature not covered elsewhere in this report include a review on the evolution of a general strategy for the stereoselective construction of polyoxygenated natural products,1 and a review of some miscellaneous topics involving synthetic reactions of carbohydrates, including syntheses of aminosugars, deoxysugars, glycosides, and the Ferrier ring synthesis.2 References 1 2

S.J.Danishefcky, Aldrichimica &, 1986, 138 108). F.Sztaricskai, I.Pelyvas, and R.Bognar, (Chem. Abstr., 1987, 106,156776).

2, 59

&.

&.

(Chem. Abstr., Lapja, 1986,

1987,

106,

5,147

2 Free Sugars Reviews covering the structural determination of carbohydrates by 1 chemical and spectroscopic means, the uses of lithium aluminium hydride-aluminiuu chloride and acidic sodium cyanoborohydride in the 2 reduction of carbohydrates and their derivatives, and chemical and biological preparations of D-ribose3 have appeared. 'The hydrogenolysis of U-glucose in aqueous and non-aqueous solution using palladium, rhodium or ruthenium catalysts supported on carbon has been investigated. Of these, only the ruthenium catalyst 0 at 2 0 0 C and a pressure of 50 bar allowed conversion of glucose 4 into iae thanol. 1.

Theoretical Aspects

Calculations of the electronic structures of a series of carbohydrates using the CiJ1)0/2 method have produced linear relationships 13 between C-n.m.r. chemical shifts and the atomic charges for the 5 o<- and p-D-glucose, d - and P-D-galactose and /3-L-arabinose systems. ivlodel systems, treated by the RHF/STO-3G method, have been used to 2 evaluate the anomeric a n d n effects in simple and 1-Q-methylpyranosides and hence derive their conformational and anomeric energies. 1,l-Dihydroxyethane and 1,l-dimethoxyethane were chosen as model 2 systems for the anomeric effect while the& effect was investigated using 1 , l ,2-trihydroxyethane and 2,2-dirnethoxyethanol.' A theoretical study of the structure of D-glucopyranose in eleven solvents by a PCILO quantum mechanical method has been carried out. 'The stability of the individual conformers was compared using a method in which the total energy is divided into the energy of an isolated molecule and the solvation energy. 'the influence of the solvent on rotation of the pendant groups and on the stability of anomers was investigated- the results were found to be in good agreement with 7' experiment. The method was further extended to the anomeric pairs 8 of all eight 0-hexopyranoses. The theoretical basis of distinguishing the configuration of the aldoses has been described using the concept of rotational symmetry. A comprehensive treatment of

3

2: Free Sugars

aldose configurations was developed in symmetry terms and presented 9 as dichotomous trees. A new kinetic model for the alkaline isomerization and degradation of monosaccharides has been presented. Computer simulations using the model fit the experimentel data and allow determination o f all relevant rate constants. The rate limiting ste appears to Yo The be enolization for both isoraerization and degradation. mechanism of redox reactions between lead hydroxide and 3-Q-methylU-glucose nas been studied by quantum mechanical calculations. 'The calculations snow that there is a redistribution of electron density in both systeus which favours the formation of a carboxyl group in 11 the C(l)-l;('j) part of the aldose. 2.

Synthesis

Peracetylated sugars treated with tributyltin methoxide gave products selectively deacetylated at the anomeric position Equatorial anomers were deprotected more rapidly and (Scheme 1). 12 u o r e selectively than their axial- counterparts. Anodic electrolysis has been used to deprotect aldose dithioacetals in good yield. CH20Ac

CH~OAC

I

I

0 Ac Reagents

OAc

L , Db3SnOMe, U , H20

Scheme 1

Other acetals were found to be stable to the cohditions. Thus ;C,3,L+, 5,b-penta-9-acetyl-D-galactose diethyldithioacetal gave 2,3,4,5,6-penta-Q-acetyl-D-galactose in 65X yield; other examples 13 quoted gave the free sugar in higher yields.

,CH20H

CHO 1

Hoj O CHZOH F OHReagvLts L,

TSCL-Py

-

CH~OTS

L

rCH2N3

u J.

('1

, U , NaN3 ,u, h v , LV, ti30+ Scheme 2

D-14annitol has been converted into D-mannose by the photolysis o f the azide (1) as shown in Scheme 2 . ' 4 Some [l-13CJaldoses have been synthesized by conventional means and used to study their 75i~IHz

4

Carbohydrate Chemistry

13

C-n.m.r. spectra.15 A convenient method for preparing pure 11 11 1 Glglucose by photosynthesis from CL) using spinach leaf 2

and hydrolysis of the labelled sucrose produced has been described. kteferences to the preparation of L 1 -13C1-enriched 5-deoxypentoses and 5-2-methylpentoses are made in Chapters 3 and 12. Sophorose has been easily prepared on an industrial scale from 17 steviosi.de by partial acid hydrolysis. 'The forrnose reaction, carried out at room tem erature in the i;b presence of calcium hydroxide, has been studied. The effects of

10

the presence of oxygen and reducing sugars on the foruose reaction using calcium hydroxide-methylene glycol have been described. The induction period was found to be shortened by reducing sugars but increased by oxygen, although the rate after induction remained the same; large quantities of added reducing sugar decreased the conversion rate. The progress of the reaction could be followed by measuring the pressure above the reaction mixture. l 9 'the same workers have carried out a detailed study of the pressure-volume changes in this reaction; the forlnation or' the complex between calciuln hydroxide and methylene glycol was accompanied by a volume contraction, which was followed by two stages of voluue increase, corresponding to the induction period and the period during which 20 sugars are formed. 'I'he isomerization of monosaccharides by aqueous potassium hydroxide under nitrogen has been monitored by liquid chrolnatography 2+ on cation(Pb ) exchange and reverse phase columns. The simple epirnerization reaction of pentoses and hexoses accounts for about YO;/, of the saccharides found in the solution after one week. 'The reuaining sugars were formed either by fragmentation or recombination; e . g . , glucose and sorbose are found in the isonerization mixtures of pentoses. The aldol reaction responsible for the formation of hexoses from dlyceraldehyde at pH 11.5 was found to be fast, thus 21 accounting for the rapid fragmentation and recombination observed. l'he previously reported rapid interconversion of D-glucose and 0uannose by nickel(I1) and i\r,fi,&l-trimothylethylenediamine(see Vol. 19, p.1~2) has been extended to other metal ions (cobalt(II), calcium, and strontium) and ~,N,J',$'-tetrainethylethylenediarnine22 (tetmen). 'The best sjstem was found to be nickel(I1)-tetmen. 'The epimerization reaction was shown to involve a 1,L-carbon shift, 13 a skeletal rearrangement, by means of C-n.m.r. of the products of ine of U&he n i c k e l ( I I ) - ~ , ~ , ~ l - t r i ~ e t h y l e n e d i a m treatment

u.,

Ll-l'Cjglucose

when the product was shown to be U-L2-l3C]mann-

2: Free Sugars

5

23

ose. Similar rearrangements were shown to occur in reactions 24 with alkaline earth or rare earth metal ions and monoamines. lvlolybdate catalyzed epimerization of D-erythro-L-manno-octose gave a mixture of D-erythro-L-gluco-octose and the starting sugar with the 25 former predominating. The metal-ion catalyzed photoreactions of sugars hich result in 2z cleavage of carbon-carbon bonds have been reviewed. Chain extension using an insertion reaction of dichloromethyllithium or dibromomethyllithium with a cyclic chiral boronate derivative, (3)-pinanedioll(benzyloxy)methyl]boronate ( 2 ) , has been used 27 in a synthesis of L-ribose in l 3 X overall yield (Scheme 3 ) . A new

synthetic equivalent ( 3 ) of the glycolaldehyde anion has been used for the two carbon chain extension of aldehydes. Thus L-ribose was synthesized f r o m 2,3-~-cyclohexylidene-L-glyceraldehyde and a boronate ( 3 ) by the addition shown in Scheme 4 . Uiaddition and higher addition reactions to yield polymers is alleviated by using a p o l l uer-supported reagent as shown in the Scheme. 'the main product gave L-ribose after deprotection. 2 8 'The observation that the proportions

*oO

@I-(0=+: fyCH0 ] Ih @+:;-fO +

(3)

0," Main

rsomer

Scheme 4

of diastereoisomers forlned in the condensation of glycolaldehyde with UL-glyceraldehyde and in the triose aldol condensation vary little with changes in the metal hydroxide catalysis has been interpreted as evidence f o r a pericyclic transition state involving &enediolate attack on the aldehyde.29 The earlier work on base-cat-

Carbohydrate Chemistry

6

alyzed condensation of glycolaldehyde and hydroxyketones

( s e e Vol.

l a , p.7) has been extended t o t h e r e a c t i o n of t h e racemic t e t r u l o s e

( 4 ) wnich g i v e s l~,L-&~x_o-3-hexulose ( 5 ) a s t h e major p r o d u c t and i t s C-2

The f o r m e r rJas i s o l a t e d a s i t s

e p i m e r a s t h e riiinor o n e .

1 , 2 : 3 , ~+-di-(-~-isopropylidene d e r i v a t i v e ( 6 ) . CH20H

to?

CC120H

b;oHl

30

HO

Ox

CHzOH

(41

0

+(5)

CH20H

(6)

Ketoses have been p r e p a r e d u s i n g t r a n s k e t o l a s e c a t a l y s i s . enzyme,

The

i s o l a t e d f r o n saccharomyces c e r e v i s i a e (balcer's y e a s t ) o r

r'rom s g i n a c h l e a f was i n v e s t i g a t e d f o r s u b s t r a t e s p e c i f i c i t y a n d i t LJas snowri t h a t i t was n o t n e c e s s a r y f o r t h e k z t o s e t o b e phosphory-

latea.

'The g e n e r a l b i o s y n t h e t i c c o n d e n s a t i o n shown i n Scheme 5 was

used i n t h e p r e p a r a t i o n of L - e r y t h r u l o s e x y l u l o s e froin 0- o r U , L - g l y c e r a l d e h y d e , ~,L-lactaldeliyde. H

L-blyceraldehyde

from , l y c o l a l d e h y d e ,

from

was n o t a c t i v e a s a s u b s t r a t e .

r e v i e w on t o t a l s y n t h e s i s o f h i g h e r h o n o s a c c h a r i d e s

t r a t e s a a i n l y on t h e a u t h o r ' s work o n t h e h e t e r o - b i e l s a c t i o n between a n a l d e h y d e and a n e l e c t r o n - r i c h

concen-

A l d e r re-

d i e n e .32

(7) o f s i m p l e m o n o s a c c h a r i d e s , p r e p a r e d

uerivatives

L)-

and 5-deoxy-0-xylulose

Viriyltin

ds shown i n

bcheme 6 , r e a c t w i t h b u t y l l i t h i u m t o g i v e t h e c o r r e s p o n d i n g v i n j l l i t h i u r n c o u p o u n d , w h i c h may be r e a c t e d lnlith a l d e h y d o s u g a r s 33 the nigher sugars. C H 20H

p

CO,

Reagents

I/,

H

CH20H

CHO

+

Rt O H

A Ho{o OH R

Tiansketolase, TPP

Scheme 5

- uun -0

/L \ O-t R e n g e h t s : L, Bu;SnH;ii,

. ..

iii,W

(7) A;iii;RuLi,Lv,

CHO

e

o O*

Scheme 6

t o give

31

2: Free Sugars

7

dsriylation of higher o c t e n o s e s , p r e v i o u s l y r e p o r t e d

( s e e Vol.

19,

Vol. 2 0 , p . 6 ) , h a s b e e n u s e d t o s y n t h e s i z e /:-L-tkhreo-l)-gluco34 and -D-gann-o-octopyranoside. I n v e r s i o n s i i t C4 a n d C 5 o f t n e h e p t o s e d e r i v a t i v e ( 8 ) u s i n g sodiuin m e t h o x i d e g a v e r i s e t o 2 , j : G , 7 - d i - G i s o p r o py 1i d e n e -/3 -L - &c e r o - L- 3 x 0- h e p t o f u r a n o s i d e ( 9 ) v i a t h e a n p.6;

h y d r o s u g a r ( l u ) a s shown i n Scheme 7 .

35

( '0) Scheme 7

Carbon-labelled

h i d h e r s u g a r p h o s p h a t e s o f t h e p e n t o s e pathway

a r e r e f e r r e d t o i n C h a p t e r 7.

3.

P h y s i c a l bieasurements

B n t h a i p i e s of combustion o f U-ribose

and 2-deoxy-&ribose

have been

i d e a s u r e d tyr bomb c a i o r i ~ f l e t r y . ~ ' U l t r a s o n i c , v o l u m e t r i c a n d v i s c o x e t r i c m e a s u r e m e n t s h a v e b e e n p e r f o r i n e d o n a q u e o u s s o l u t i o n s o f U.lucose

a n d 0-mannose

a t 20

0

0

a n d 30 C .

These measureinents were

u s e d t o e v a l u a t e i m p o r t a n t u l t r a s o n i c and thermodynamic p a r a m e t e r s i n c l u d i n g a p p a r e n t and 2 a r t i a l m o l a l volume, a p p a r e n t and p a r t i a l lnolal c o m p r e s s i b i l i t y , v i s c o s i t y S - c o e f f i c i e n t s

o f t h e Jones-Uoie

e q u a t i o n , a n d c h a n g e s i n f r e e e n e r g y , e n t r o p y , aiid e n t h a l p y o n d i s solution.

The 2 a r a m e t e r s w e r e u s e d t o e x p l a i n t h e p r e d o m i n a n t

solute-solvent

interactions.

37

h a t e c o n s t a n t s f o r t h e t a u t o m e r i z a t i o n of >-hydroxypentanal have u e e n d e t e r m i n e d by l i n e s h a p e ' 3 C - n . ~ n . r . r o t a t i o n of U-fructose t h e two p y r a n o s e ,

t h e ,4-> y r a n o s e t o / ? - f u r a n o s e

34L

'The inuta-

two f u r a n o s e a n d t h e o p e n c h a i n forrus h a s b e e n r e -

e x a m i n e d by g . ~ . a n d g . ~ . - m . s . utor.

analysis.j8

t o a f i v e colnponent e q u i l i b r i u m m i x t u r e o f of p e r t r i m e t h y i s i l y l a t e d

samples,

e q u i l i b r i u m b e i n g t n e major c o n t r i b -

The m u t a r o t a t i o n o f l ~ - g l u c o s e i n sorue malumalian body f l u i d s

n a s been measured u s i n g 1 - g l u c o s e

oxidase-rnutarotase

and polarimetry.

i'he m u t a r o t a t i o n was more r a p i d t h a n i n d i s t i l l e d water i n many 40

cases.

A l l

s i x t a u t o m e r s of D-glucose i n aqueous s o l u t i o n s have been

d e t e c t e d and q u a n t i f i e d using h i g h r e s o l u t i o n

13

C n.m.r.

on

D-

8

Carbohydrate Chemistry

[ ~ - ' ~ ~ ] g l u c o s4'e . I3C-n.rn.r. h a s a l s o been u s e d t o d e t e r m i n e t h e p r o p o r t i o n s of p y r a n o s e a n d f u r a n o s e f o r m s i n a q u e o u s s o l u t i o n s o f t h i r t e e n m o n o s a c c h a r i d e s . 42

E q u i l i b r i u m t a u t o m e r s of a l l o s e ,

a l t r o s e , g u l o s e , i d o s e , and t a l o s e have been a n a l y z e d a s t h e i r t r i i n e t h y l s i l y l e t h e r s by c a p i l l a r y g . ~ . A l d o p e n t o s e s were a l s o examined.

ti.c.-m.s.

ents.43

The p r o p o r t i o n s o f f u r a n o s e a n d pyrariose r i n g f o r m s i n

and n.rn.r.

were u s e d t o i d e n t i f y t h e compon-

UIVISO s o l u t i o n s o f g l u c o s e , g a l a c t o s e , a r a b i n o s e a n d J-g-(d- a n d /j-D-galactopyranosyl)-U- and - L - a r a b i n o s e have been d e t e r m i n e d by liakamori l a e t h y l a t i o n and E c.-m. ;. s . a n a l y s i s o f t h e i r d e r i v e d inethylateci a l a i t o l a c e t a t e s . The v a l u e s would a p p e a r t o r e p r e s e n t t h o s e 44 o b t a i n i n g under t h e c o n d i t i o n s of t h e methylation procedure. h.m.r. s t u d i e s s u p p o r t t h e i d e a t n a t U - f r u c t o s e e x i s t s m a i n l y a s t h e , 3 - f u r a n o s e i n l)PiSu due i n p a r t t o t h e Ud-I t o U k I - 4 h y d r o g e n bond, a s p r e v i o u s l y s u g g e s t e d ( s e e V o l . 1 9 , p . 4 ) . However, a n i m p o r t a n t f a c t o r , a s t h e a u t h o r s s u g g e s t , i s t h e i n f l u e n c e of t i l e uediurn on t h e f r e e e n e r g y of t h e b - p y r a n o s e f o r m , which p r e d o i a i n a t e s i n aqueous s o l u t i o n ; changes i n t a u t o m e r i c composition i n m i x t u r e s o f Divl5;O and w a t e r i n d i c a t e t h a t s p e c i f i c s o l v a t i o n by w a t e r i s t h e Tre]:lain f a c t o r i a s t a b i l i z a t i o n o f t h e /3-pyranose f o r m . 4 5 rialuiose (I-g-tx-D-glucopyranosyl-b-fructose), i s o l a t e d by p r e p a r a t i v e r e v e r s e d - p h a s e h l ' L C from t h e c r y s t a l l i z a t i o n l i q u o r s o f i s o m a l t u l o s e , 13 Has been shown by C-n.m.r. t o e x i s t a s a 2 : l m i x t u r e o f t n e 146 f r u c t o p y r a n o i a and P - f r u c t o - f u r a n o i d f o r m s i n w a t e r . An i n g e n i o u s e x a m i n a t i o n o f t h e a b i l i t y of t n e anorners o f t h e e i g h t 2-aldohexo s e s t o form h y d r o g e n bonds t o w a t e r h a s a l l o w e d a r a t i o n a l i z a t i o n o f t h e i r d:,4 r a t i o s i l l a q u e o u s s ~ l u t i o n . ~ kiy ' ~ means o f a k i n e t i c s t u d y o f s t a n d a r d arnide h y d r o l y s e s i n a q u e o u s c a r b o h y d r a t e s o l u t i o n the carbohydrate-solvent interactions causing inhibitory k i n e t i c e f f e c t s have been e v a l u a t e d . Whilst d i i u t e s o l u t i o n s o f s e v e r a l l ' r e e s u g a r s show a l m o s t i d e a l thermodynamic b e h a v i o u r , o t h e r a f f e c t s a r e a t t r i b u t e d t o sugar-induced a l t e r a t i o n s i n t h e three-dimensional 48 11-bonded s t r u c t u r e o f w a t e r . An i n s i t u e . s . r . s t u d y o f t h e f o r m a t i o n a n d s t r u c t u r e 0 2 r a d i c a l s from U - r i b o s e a n d 2-deoxy-U-ribose h a s shown t h a t r a d i c a l s a r e formed a t C - I , C - k , a n d C - 3 b;r h y d r o g e n a b s t r a c t i o n f o l l o w e d by r e g i o s e l e c t i v e d , p - w a t e r e l i m i n a t i o n , t h u s g i v i n g 2-deoxyribonoi a c t o n y l , l-deoxypentopyranos-2-u~os-l-~l and 4-deoxypentopyranos-

49 3-~10~-L+.-jl.

Construction of a n a p p a r a t u s f o r measuring e l e c t r o c a p i l i a r y curves of t h e mercury-electrolyte

i n t e r f a c e b a s e d on t h e maximum

2: Free Sugars

9

bubble p r e s s u r e technique has allowed t h e study o f t h e a b s o r p t i o n of b-xylose,

D-ribose,

fluoride interface. $-Irradiation e.s.r.

a n d s u c r o s e a t t h e uercury-0.7953N

50

o f <-D-glucose

a t '77-41

sodium

5K h a s b e e n i n v e s t i g a t e d by

a n a l y s i s , which showed t h a t t h e c h a i n r e a c t i o n was p r o p a g a t e d

from i n i t i a l l y formed r a d i c a l s by d e c o m p o s i t i o n t o s u g a r a c i d s a n d 51 by dehydration t o y i e l d secondary r a d i c a l s . Oxidation

4.

' l h e k i n e t i c s of t h e o x i d a t i o n o f D - g a l a c t o s e , u-fructose,

L-sorbose,

L-arabinose,

U-ribose

2)-glucose, a n d u-,;ylose

U-mannose, with

u e r i u u ( IV) i n p e r c h l o r i c a c i d showed t h a t two complexes were formed i n each case.

The f i r s t forins i n a p r e - e q u i l i b r i u m r e d c t i o n d u r i n g

u i x i r l g arid i s p a r t l y o x i d i z e d v i a i l i c ~ i a e l i s - i ' i ~ : n t o nK i n e t i c s tilid p a r t l y d i s s o c i a t e d t o t h e second.

;lowly

t h a n trie f o r m e r .

The l a t t e r i s o x i d i z e d more

'I'he pseudo f i r s t o r d e r r a t e c o n s t a n t i n 1 .UPI

p e r c h l o r i c a c i d was a l m o s t c o n s t a n t o v e r t h e r a n g e o f s u g a r c o n c e n t r a t i o n s 0 . 1 ~ 1t o 1.01~1, from which i t was c o n c l u d e d t h a t p r a c t i c a l l y 52 a l l t h e c e r i u m ( 1 V ) was complexecl. Kinetic parameters l o r t h e o x i d a t i o n o f 0 - l y x o s e by i r o n ( l . 1 1 ) alid ceriurn(1V) s u l p h a t e s have been d e t e r m i n e d .

Both r e a c t i o n s a r e f i r s t o r d e r i a o x i d a n t , a n d

v a r i o u s o r g a n i c a c i d s a r e p r o d u c e d . 53 riiolar e q u i v a l e n t o x i d i z e s Li-fructose

'Tnalliuin( 111) i n a t w e l v e completely t o carbon uioxide.

J'ormaldehyde and f o r m i c a c i d a r e forined a s i n t e r u e a i a t e p r o d u c t s , t h e r a t e o f o x i d a t i o n b e i n g s t r o n g l y i n h i b i t s u by t h e p y e s e n c e 01'

c h l o r i d e o r a c e t a t e ioris.

oxidation

01'

b-fructose

''

I'he i r i n e t i c s arid inechanisin o f

by c o p p e r - p f r i a i n e

couplex i n excess Gjrid-

i n e h a v e been s t u d i e d s p e c t r o p h o t o m e t r i c a l l j .

'The o b s e r v a t i o n t h a t

t h e r a t e of o x i d a t i o n was e q u a l t o t h e r a t e or' e n o l i z a t i o n l e d t o t h e p r o p o s d l t h a t t h e r e a c t i o n s p e c i e s was t n e e n e d i o l a t e a n i o n .

35

icuthenium( 111) c d t a l y z e d o x i d a t i o n or' a l d o s e s by ilbS h a s been s t u a i e d i n aqueous a c e t i c a c i a i n t h e 2resence of rnercury(I1) aceL a t e and s u l p h u r i c a c i d .

i'he r e a c t i o n was f i r s t o r d e r i n i4bS but

t h e o r d e r i n a l d o s e c o n c e n t r a t i o n changed f r o i n one t o f r a c t i o n a l i n t h e presence of t h e c a t a l y s t s . s p e c i e s i s t h e d-anoner dalactose,

b-mannose,

i t was s u h g e s t e d t n a t t h e r e a c t i v e

i n the 3-series;

and d - , l u c o s e

oxidation decreasing i n t h e order given.

oy p o t a s s i u m brolnate

D-arabinose,

u-xylose, U-

were e x a a i n e d , t h e r a t e or'

50

Oxidation of 0-xylose

i n d i l u t e s u l p h u r i c a c i d t o g i v e U-xylonic

a c i d h a s b e e n s t u d i e d k i n e t i c a l l y , a n d t h e thermodyriainic c o n s t a n t s

Carbohydrate Chemistry

10 determined.

57

The c h a n b e s i n a s c o r b i c a c i d i n d u c e d G;r o x f g e n h a v e

I t was f o u n d t h a t t h e r a t e o f o x i d a t i o n i n c r e a s e d

been examined. vritn

~JH,

d e c r e a s e a i n t h e p r e s e n c e o f g l u c o s e , was s l i g h t l y i n c r e a s e d

by m a l t o s e ,

''

vrhile t h e p r e s e n c e or' t a r t a r i c a c i d c a u s e d l i t t l e

O x i d a t i o n o f a s c o r b i c a c i d by i n o l e c u l a r o x y g e n c a t a l y z e d 60 b y c o p p e r ( 11)59 a n d by c o p p e r ( 11) g l y c i n e p e p t i d e s h a s been s t u d i e d .

change.

ihe p e r t e c h n a t e i o n o x i d i z e s a s c o r b i c a c i d t o mlhic h

a red species

c o lil p r i s e s t e c hn e t i urn ( V ) -d e h y d r oa sc 0 r ba t e c o m p 1e x

.

ii i n c

t ic s o1

t n e r e a c t i o n d e r e measured and Arrhenius p a r a m e t e r s Qere o b t a i n e d . H c y c l i c voltammetric

01

s t u d y o f Lldcose o x i d a t i o n o n a n o x i a e -

covered p l a t i n u m e l e c t r o d e i n t h e g r e s e n c e o f an u r i d e r p o t e n t i a l u e p o s i t e d t h a l l i l - l n l a j e r lids b e e n ~ e p ot ra d .

bd

'Ine i n t e r f a c i a l mass-

t r a t i s f e r o f m e u i a t o r s o l a l l o d i c o x i d a t i o n or' g l u c o s e usin;: =ild h j p o b r o m i t e

bromide

i o n s a s t h e r e d o x i l l e d i a t o r s ~ i a st e e n s t u a i e d .

Both

the experimental r e s u l t s a d the t h e o r e t i c a l analysis indicate tiiat the r a t e o f o x i d a t i o n is i n u e p e n d e n t o f

but i s sidnificant.L;

t h e .lucose

concentration

a f f e c t e d by t h e i r i t r a f a c i a l lrlass t r a n s i e r a n u

tile i n i t i a l c o n c e n t r a t i o n of ! l i e d l a t o r ,

the r a t i o o f t n e s u r f a c e a r e a

of: t h e e l a c t r o d e t o t h e vdldme of: s o l u t i o n , arid t n e r d t e of

g e u e r a t i o n oi' a c t i v e I s e c l i a t o r .

02

un t i l e b a s i s o f a K i n e t i c s t u d y , t h e mechanism o f o x i d a t i o n o f l a c t o s e by l i e s s l e r I s r e a d e n t lili

in

a l k a l i n e iaddium h a s been G r o p o s e d .

e n e d i o l i r i t e r n e d i a t e with r i i e r c d r y ( l 1 ) t r i i o d i d e i o n a s trie r e -

d c t i n g s p e c i e s were i n v o k e d .

04

i L e i e r e n c e t o t h e d e g r a d a t i o n o f s o n 8 d i s a c c h a r i d e s by a l i - , a l i n e iiy'cirogen p e r o x i d e i s made i n C h a p t e r 3 .

5. A

ci t

h e r rteact i o n s

s p e c t r o p h o t o m e t r i c ldethod has b e e n u s e d t o s t u d y t h e L o b r y d e

uruyn-Alberda o f iLterconver

been measured.

van h k e n s t e i r i r e a c t i o n of 0 - g l u c o s e , i o n o f U-,lucose,

g5

0-fructose,

and t h e k i n e t i c s

a n d 0-mannose

have

A d e t a i l e d s t u d y o f t n e mechanism o f % h e

a L K a l i n e d e g r a d a t i o n of m o n o s a c c h a r i d e s has b e e n c a r r i e d o u t . A

66

s t u d j o f t h e b o n d i n g o f soaiuril i n the s o d i u m c n l o r i d e , b r o m i d e ,

dnd i o d i a e a d a u c t s or' s u c r o s e h a s b e e n u n d e r t a K e n u s i n g i . r .

s p e c t r a .67

P a r t i a l l y s u l p n o n a t e d p o l y v i n y l a l c o h o l s have been

shown t o b e b e t t e r c a t a l y s t s f o r t h e n y d r o l y s i s of s u c r o s e t h a n sulphuric acid. I'he h y d r o l y s i s r a t e was h i k h e r w i t h s y r i d i o t a c t i c PVA d e r i v a t i v e s t h a n w i t h i s o t a c t i c o r a t a c t i c PVA 2 a r t i a l s u l p h o n ates.

b8

11

2: Free Sugars R e fe r ences 1

2 3

4

5 b

7 0

9 lU

11 12 13 14 15

w.

L.Kenne, Stud. Org. (Amsterdam), 1460, &, 1 9 9 ( C e i . A b s t r . , 1 9 8 7 , 1&, 196 b d l ) . A . L i p t a k a n d Z.Szurinai, 14agy. Ken. Lap-ja, 1980, 4-1, Z2U Abstr., 1987, tJ7 5 7 5 ) . V . I . N i f o n t o v , K.1 . A K i s h i n a , A .I] . G r i s h a k o v , a n d A.Pl.Yurkevich, Khirn.5. Z L , 1 9 3 7 , 2 l , 599 (Chem. A b s t r . , 1 9 8 7 , 1 0 7 , 5 5 333). l l . A r i o n o , C.I\ioraes d e Abreu, A . R o e s y a d i , G . k c l e r c q , a n d A . % o u l a l i a n , B u l l . SOC. Chim. &, 19d6, 7 0 3 A b s t r . , 1 9 8 7 , 1_&7, 7 8 155) A.Z.Uzhurnanazarova, I . A . A b r o n i n , il.K.Osmanaliev, a n d V.A.Afanas'ev, Izv. Akad. -h a u k Kirx. !&, 1 9 8 5 , 4 2 (Chern. A b s t r . , 1 9 8 7 , H J:, 156 7tju). P . K a l i a n n a n , S . V i s h v e s h w a r a , a n d V.S.K.Ilao, P r o c . - I n d i a n Acad. Cliem. S c i . , 1986, YJ, 327 (Chem. A b s t r . , 1 9 d 7 , 106, 4309). 1 . T v a r o s k a a n d 'I'.Kozar, T h e o r . Chim. Acta, 1 9 8 6 , 7_0, 9 9 A b s t r . , 1 9 8 7 , l ~ o 1, 7 6 7 5 2 ) . i'P. (Chem. Z v e s t i ) , 1 9 6 7 , 41, 465. I.'l'varoska a n d 'I'.kozar, R . B e n t l e y a n d J.L.Popp, J. Chem. Cduc., 1 9 8 7 , 64, 15 (Chem. A b s t r . 1Yd7, l&, l l d 3 1 2 ) . J.i*i.de b r u i j n , A.P.G.Kieboom, a n d II.vsn Uekkum, Kecl. T r a v . Chim. Pays-Bas, 1 9 6 7 , 1 2 6 , 35 (Chem. A b s t r . , 1 9 8 7 , u7, 115 858). K.A.GaKhokidze a n d N.S.Vashakmadze, S o o b s h c h . Akad. i h u k G r u z . SSK, 1480, 1 2 , 3 2 1 (Chem. A b s t r . , 1 9 8 7 , l U Q , 150 7 7 9 ) . h.Nudelman, J . H e r z i g , H . E . t i o t t l i e b , E.Keinan, a n d J . S t e r l i n g , CarbohyJr. &, 1 9 8 7 , 162, 1 4 5 . A.Lebouc, J . S i n o n e t , J.Gelas, a n d A.Uehbi, S y n t h e s i s , 1 4 d 7 , 32U. h . P e t r u s o v a , N.Yedoronko, a n d L . P e t r u s , Chcm. P a p . , 1 9 8 0 , $0, b55 (Chern. A b s t r . , 1 9 8 7 , 12Y 0 3 8 ) . n . J . K i n g - k i o r r i s a n d A . S . S e r i a n n i , J. Ciiein. S O C . , 1 3 8 7 , lA9,

(m.

z,

(m.

w, (m.

=.

m,

&I.

35b1.

K . I s h i w a t a , r ~ . ~ l o n m aa, n d T.1~0,A p p l . K a d i a t . I s o t . , 1 9 8 7 , L U , 475 (Chem. A b s t r . , 1 9 8 7 , l L 7 , 1 1 2 1 4 8 ) . 1 7 I . K u s a k a b e , S.Kusama, a n d K . ~ i u r a k a m i , Agric. b i o l . Chem., 1 9 6 7 , '1, 2255. I d T . J i a n g , T . L i , a n d C.Wu, t i u a n j i n g Huaxue, 1%b, 5 , 63 (Chem. A b s t r . 1 9 ~ 7 ,Ic)b, 102 0 2 4 ) . 233 19 H.W.i\laurer, J . i d . b e n i i l l e r , a n d G.V.Smith, J. C a t a l . ; l4tr7, (Chem. A b s t r . , 1967, g 7 , 134 5 6 4 ) . 2u ti.W.i\iaurer, J . N . b e m i l l e r , a n d G.V.Smith, J. C a t a l . , 1Yb7, u 3 , 474 (Chem. A b s t r . , 1 9 b 7 , u 7 , 134 505). H.S.El Khacien, S . E n n i f a r , and h . S . l s b e l 1 , C a r b o h y d r . lY87, Ll 13. L L 'l'.'Tanase, F . S h i m i z u , h. Kuse, S. 'Yario, S .YosniKawa, a n d ivi.kiidai, J. Chem. S O C . , Chern. Comrnun., 1 9 6 7 , 6 5 4 . Chem. SOC., Chem. Commun., 1Y87, b b l . L 3 R.E.London, L4 'I.'l'anase, ' T . h u r a t a , S.Yano, h . h i d a i , a n d S . Y o s h i ~ a w a Chem. L e t t . , 1 4 6 7 , 14b4. L5 V . k j i l i K , J . A l l o l d i , a n d i.l.i*latulova, Chen. P a p . , 1980 A b s t r . , 1Y87, x 7 , 1 7 b 320). L D 5.i c h i k a w a a n d 'r. S a t o , YuKi h o s e 1 KaqaKu K y o k a i s h i , A b s t r . , 1487, 1 0 7 , 23 Sd0). L7 l).S.blatteson a n u i'i.L.Peterson, J . ~ r g Chem., . 1467, 52, 5 l l b . L8 b . W u l t t a n d A.Hansen, C a r b o h y d r . =,1 9 d 7 , k 4 , 1 2 3 . LC) S . N o r g e n l i e , J. C a r b o h y d r . Chem., 1 9 8 7 , 2, 001. 31, S . l . l o r g e n l i e , Acta Chem. S c a n d . , k.2, 1 9 b 7 , 5 , 745. 31 J . k j o l t e , C.Ueinuynck, a n d tI.Samaki, T e t r a h e d r o n L e t t . , 1 9 d 7 , 2&, 5525. 9. Bncll., 32 S . J . U a n i s h e f s k y a n d ki.P.De N i n n o , Angew. (;hem. 1 9 8 7 , &, 15. 1 9 8 7 , *, L11. 33 S . J a r o s z , L a r b o h y a r . lb

z,

w,

-

J.

(e.

&.

a,

m,

Carbohydrate Chemistry

12 Carbohydr. 34 J.S.8rimacombe a n d A.K.M.S.Kabir, 35 J.S.brimacombe a n d A.K.ivl.S.Kabir, L a r b o h y d r . 36 J . C . C o l b e r t , g.S.l)omalski, a n d B.Coxon, J. 1 4 , 433 (Chem. A b s t r . , 1Y87, 1 0 7 , 1 1 5 863).

&,

158/,

M,

c5.

a, 1 9 8 7 , lb(J, 234. *. Thermodyn., 1 9 8 7 ,

37

38 JY 40

41 42

43 44

45 40 *7 48

49

5u 31 52 33

54

55 30

57

5d 3Y

uu 01 u2 03

u4

x O . P a n d e y a n d A.ShuKla, k c o u s t . L e t t . , 19d6, 4 , 15b (Chem. A b s t r . , 1 9 8 7 , X b , 140 092). J . B u d d r u s , ivl.Jablonowski, a n d A . b r i n k r n e i e r , L i e b i g s Ann. Chem., 1 9 8 7 , 547. M.Cockman, lJ.G.Kubler, A.S.Oswald, a n d L . W i l s o n , J. C a r b o h y d r . 1 9 8 7 , 4, 181. J.Okuda, T . T a g u c h i , a n d A.'l'omimura, Chem. Pharm. B u l l . , 1 9 8 7 , 35, 4332. S.K.Maple a n d A . A l l e r h a n d , J. Chem. S O C . , 1 9 8 7 , 1 2 , 3168. K.Perez Key, H.Velez C a s t r o , J . C r e m a t a A l v a r e z , L . F e r n a n d e z M o l i n a , a n d J.Hormaza h o n t e n e g r o , I(ev. C i e n c . (cuim., 1 9 8 5 , lb, 225 A b s t r . , 1 9 8 7 , g 7 , 237 1 4 1 ) . r l . P a e z , 1 . P i a r t i n e z - C a s t r o , J . S a n z , A.Olano, A.Garcia-Kaso, a n d F . S a v r a i a l i x t o , C h r o m a t o g r a p h l a , 1 9 b 7 , &, 43 (Chem. A b s t r . , 1 9 d 7 , 1 0 0 , 2 ~ 6940). J . H . P a z u r , F.J.IYliskie1, a n d B . L i u , J. C h r o m a t o g r . , 1 9 8 7 , 3 2 , 139. P.l)ais a n d A . S . P e r l i n , C a r b o h y d r . k, 1 9 8 7 , 169, 159. l).Coo&cson, P.S.J.Cheetham, d n d E . B . g a t h b o n e , J. C h r o n a t o g r . , 1967, 4 0 2 , 203. i ~ . l ) . d a l ~ i n s h a w ,J. Chem. SOC., P e r k i n T r a n s . 2,1 9 8 7 , 1 4 U j . J . J . h . n u s s e l a e r a n d J.U.F.N.Bngberts, A. I)rg. Chem., l W 7 , 5 2 , 31>9 J . H . h e r a k a n d b . B e h r e i i s , 4. i l a t u r i o r s c h . , c: B i o s c i . , 1 9 8 b , 5, IOU;! (Chem. A b s t r . , 1 9 8 7 , g 6 , 1% 7 8 3 ) . K . P a r s o n s a n d K.?eat, P r o c . - i n a i a n Acad. S c i . , Chem. S c i . , l r d o , 4 7 , 333 (Chem. k b s t r . , 1 9 8 7 , 1 2 , 1U4 8 8 4 ) . c V . a b a g y a n a n d S.pi.Atasnyan, A r m . h i m . Lh., i Y 8 7 , G , 3 A b s t r . , l r o l , 1 0 7 , ~ 1 942). 7 P . O l a v i , I . V i r t a n e n , K . ~ i n d r o o s , b . O i K a r i n e n , a n d J . \ ( a S h U T i , Carbollydr. &, l Y a 7 , &7, 29. V . i . k r u p e n s K i i , 2.Obshch. Khim., 1980, 2, ~ 4 1 L(Chem. k b s t r . , 1 9 6 7 , 1 0 7 , 134 5 5 5 ) . quim., lgbb, 5 A.L.fladnis a n d b . K . S h r i v a s t a v a , (Chem. A b s t r . , 1 9 8 7 , 106, i Y 6 0 8 7 ) . A .I( . S i n g h , A . K. S i s o d i a , A. Parniar, lvi.Saxena, and P .S . d a j p a i , Acad. ( I n d i a ) , 19db, 2, 3UY (Chem. A b s t r . , 1 9 8 7 , g 7 , 96 ~ 4 2 ) . I . K i s t a y y a , M.S.Keddy, a n d S . d a n d l i k a r , I n d i a n J . Chem., S e c t . iy&$o, ~ 5 '105 , (Chem. A b s t r . , 1 9 8 7 , I s , 1 7 7~5 5 ) . S.I.c.bhukla a n d C . D . B a j p a i , i i e a c t . K i n e t . C a t a l . L e t t . , lYdb, 0, 309 ( C k m . A b s t r . , 1 9 b 7 , 1% W b ) . P . K o l a r , $aria. V e s t n . ( L i u b l i a n a ) , 19th. g , l b l (Chem. A b s t r . , lY87, Ic)b, l b L b h ) . F.Zhang, Y-Lhang, J . L i u , a n d X.Zhao, N u l l Huaxue Xdebao, 1400, 2, 332 (Chem. A b s t r . , 1 4 b 7 , l u L b23). n.Cheng a n a Y.Pang, k a o x u e L u e b a o , 1460, 4 , L 9 1 (Cnern. A b s t r . , lY87, I d 471). r'.clrases, C . L e n e s t a r , a n d o . ~ m a t , A. Cnem. K l n e t . , 1960, l_d, 699 (Chem. A b s t r . , 1907, k , 130 W l ) . p1.J . b h a o , X . K .Xing, a n d C.C. L i u , b i o e l e c t r o c n e m . d i o e n e r g . , 1 9 6 7 , 17, 29 (Chem. H u s t r . , 14t;/,1 x 7 , 115 b t 7 ) . h.Comoun., 1407, 1'.C.Chou, J . S . b o , B . ~ . h w a n y , a n d J . J . J o w , 51, 4 / (Ciierrr. A b s t r . , 1 9 6 7 , 1 2 , L L L b L 4 ) . 19i.P . A i n g n , K. K. S i n g h , A . 6.S i n g h , A. K. S i s v u i a , a n d ivl.Saxeiia, Acad. S c i . L e t t . ( I n d i a ) , l Y 8 6 , 2 , ~ 7 (Cnem. 7 Abstr., 1987, k 7 ,

=.

&.

(m.

-

(m.

&.

=.A,

a,

&.

- &. &.

A,

m,

m,

m,

-

Yu Y Y 3 ) .

x.

w.

&.

2: Free Sugars

13

69

H.L.Mirza, Y.ul H.IJasim, and k.Akram, 1T_. Pure Appl. Sci., 1905, 4, 9 (Chem. Abstr., 1967, &7, 115 85b). J.iq.de Bruijn, A.P.G.Kieboom, and H.van BeKkum, Starch/StaerKe, 1987, 2, (Chem. Abstr., 1987, 1 2 , 120 154). K.'l'ajmir and A.Heidar, J. Coord. Chem., 196b, 15,95 (Cnem. Abstr. 1467, &, 00 270). S.Matsuzawa, K.Yamaura, K.Yanamoto, T.Katoh, S.Kawaguchi, and ~ . k i y a k e , J. Polym. Sci., Part C: Yolym. Lett., 1 9 b , Z_q, 533 Abstr. 1987, 1&, 1.20 100). F.G.Njoroge, L.k.Sayre, and V.ivl.kionnier, Carbohydr. &, 1967, x 7 ,

7U

R.fliller, Acta Chem. Scarid., Ser.

65

60

u7 b8

(w.

Lll.

B, 1987, 41,

208.

3 Glycosides and Disaccharides 1

O-Glycosides

1.1 Synthesis of Monosaccharide G1ycosides.- A review has been published on the synthesis of glycopeptides which covers aspects of glycoside formation and the linkage between sugars and serine o r 1 serine-containing peptides. Tetra-O-benzyl-a-D-glucopyranosyl .dimethylphosphinothiolate reacts with alcohols in the presence of silver perchlorate at room 2 temperature to give good yields of mainly a-linked products. Another novel approach to the preparation of hexopyranosides involves the use of alkoxymethylene Horner Wittip reagents applied to 2,3,5-tribenzylpentoses (Scheme 1). From the E-alkene products

1

R e a g e n t : 1, MCPBA

R=Me

82%

64.36

86%

90

10

R'=R'

61%

6 0 16*

01%

85

15

Scheme 1

*a450 2 4 % s-D-Manno

mixtures of 1,2-trans-related glycosides were obtained, whereas the Z-isomers led to 1,2-+-glycosides. Simple 02' carbohydrate Horner Wittig reagents could be used. 3 A simple and high-yielding synthesis of vinyl and substituted vinyl B-D-glucopyranosides is illustrated in Scheme 2,4 and three

-

reports have appeared on the preparation of related acetal glycosides which can be made in high yields and with good anomeric

15

3: Glycosides and Disaccharides CH20Ac

0Ac Reagent

'

L,

Hy (CH2COR)2

Scheme 2

s e l e c t i v i t y as i n d i c a t e d i n Scheme 3 .

The t e t r a b e n z y l s i l y l a-

g l y c o s i d e can a l s o be used, b u t i t i s less r e a c t i v e and cannot b e CH~OAC

AcO@*TM+

RCH(OM4,

OAc

:>1

+

,OMc COCHR

--&

MeOTMS

R = H , Pr,Bn, CH20Me,CH2CL

R e a g m i, T M S O T f

(-Toot)

Scheme 3

obtained anomerically pure.

D i a s t e r e o i s o m e r s a t t h e new a s y m m e t r i c

c e n t r e w e r e f o r m e d i n t h e a p p r o x i m a t e r a t i o o f 3:1.5

The r e a c t i o n

i s a l s o a p p l i c a b l e to t h e 6- i s o m e r o f t h e s t a r t i n g m a t e r i a l a n d

c a n b e g e n e r a l i z e d by u s e o f a n y a c e t a l s o f a n y a l d e h y d e ; a l t e r n a t i v e l y , t h e u n p r o t e c t e d compounds ( 2 ) c a n b e made f r o m t h e s i l y l B-glycoside

4.6

(1) as shown i n Scheme

OH

OAc (2)

(1)

~eng-

The p r o d u c t s c a n b e

i, RCHO, R'OTMS.TMSOTF Scheme 4

~

&,

M ~ O -

h y d r o l y s e d by a c i d o r e n z y m i c a l l y t o r e l e a s e t h e a l d e h y d e s . C y t o t o x i c aldehydes which cannot themselves b e used c l i n i c a l l y because of binding t o p r o t e i n s can be administered i n t h e a c e t a l g l y c o s i d i c form.

The a m i n a t e d compounds ( 2 ) , ( R = ( C H 2 ) n N H 2 ,

1 R =Me,

n = 1 - 4 ) h a v e b e e n made by a c e t a l e x c h a n g e f r o m (1) v i a t h e w-bromides and a z i d e s , g i v i n g p o t e n t i a l f3-glucosidase i n h i b i t o r s . The a m i n e s

were r e s i s t a n t t o e n z y m o l y s i s w h i l e t h e i r s y n t h e t i c p r e c u r s o r s t h e bromo o r a z i d o a n a l o g u e s - were h y d r o l y s e d . 7 The p o t e n t i a l l y u s e f u l o b s e r v a t i o n h a s b e e n made t h a t w h i l e t r e a t m e n t o f methyl a-D-gl.ucopyranoside

w i t h b e n z o i c a c i d , tri-

p h e n y l p h o s p h i n e a n d d i e t h y l a z o d i c a r b o x y l a t e i s known t o g i v e t h e 6-benzoate,

s i m i l a r t r e a t m e n t o f t h e B-anomer a f f o r d e d , a f t e r

Carbohydrate Chemistry

16

hydrolysis, only methyl B-D-allopyranoside; similarly, methyl B-Dxylopyranoside gave methyl B-D-ribopyranoside. 8 Synthesis of n-alkyl B-D-mannofuranosides from C 7-16 n-alkanols bromide has and 2,3:5,6-di-~-ethylboranediyl-a-D-rnannofuranosyl given mesogenic compounds of potential value as liquid crystals.9 The cyclohexyl glycosides ( 4 ) and ( 5 ) have been made in the ratio 60:40 by condensation between the 1-butadienyl glycoside ( 3 ) and acrolein (Scheme 5 ) . The reaction was carried out in water and

had rates and selectivities which were enhanced relative to those for the reaction of the corresponding tetra-)-acetate in non-polar solvents. The sugar was removed enzymically to allow access to 10 optically pure cyclohexane derivatives, e . g . , the new diol (6). Considerable attention has been paid to the further development of routes to glycosides of 2-ulosonic acids. Treatment of the alkene ( 7 ) with m-chloroperbenzoic acid gave ( 8 ) as the only glycoside formed ( 45%),11 and the glycosyl fluoride ( 9 ) has been

OH (11)

R

= M~(CHZ),CO,

n = 16 or 22

applied to the preparation cf a-glycosides, including disaccharides, of KDO.l2 Most attention, however, has gone into the synthesis of glycosides of neuraminic acid: the glycosyl chloride (10, R=H) has been used to obtain the E-nitrophenyl a-glycoside , I 3 the corresponding ally1 compound and hence the formylmethyl analogue required f o r reductive-amination coupling to proteins ,I4 and the ceramides (11).l 5 An alternative approach to a-glycosides of the series uses the

17

3: Glycosides and Disaccharides

h y d r o x y compound (10, R=OH) a n d s u b s e q u e n t C - 3 d e o x y g e n a t i o n by way o f t h e p h e n o x y t h i o c a r b o n y l d e r i v a t i v e ,I6 a n d a f u r t h e r method employs t h e 3 - s e l e n o g l y c o s y l

f l u o r i d e (121, made from t h e 2-ene

f o l l o w e d by e p i m e r i z a t i o n o f t h e s e l e n o - g r o u p

Reagents: L, D A S T ; i,ROH -AgOTF -5nCL2 ; %, Ou g Sn H

(Scheme 6 ) .

17

; W, H * - P d / C

Scheme 6

A l t e r n a t i v e l y , B-glycosides

have been o b t a i n e d u s i n g t h e

d i b r o m i d e ( 1 3 1 , t h e s e c o n d b r o m i n e atom o f which p r e v e n t e d e l i m i n a t i o n a n d p r o v i d e d s t e r i c h i n d r a n c e on t h e a - f a c e o f t h e m o l e c u l e , and a l s o t h e 2,3-epoxide

(14), which p r e f e r e n t i a l l y u n d e r g o e s

r i n g opening with a l c o h o l s i n a c i d c o n d i t i o n s .

18

cis-

The h y d r o x y l g r o u p

0

1741

(13)

('5)

I n both a t C-3 was s u b s e q u e n t l y removed by r a d i c a l m e t h o d s . l9 t h e s e c a s e s t h e s t r a t e g i e s were a p p l i e d i n d i s a c c h a r i d e s y n t h e s e s . P e r a c e t y l a t e d g l y c o s y l c h l o r i d e s or f l u o r i d e s h a v e b e e n u s e d t o prepare

s t e r o i d a l g l y c o s i d e s o f N-acetyl-D-neuraminic

optimum c o n d i t i o n s were f o u n d 20 B-linked p r o d u c t s .

a c i d , and

f o r f o r m i n g b o t h t h e a- a n d t h e

S e v e r a l r e p o r t s h a v e a p p e a r e d on t h e s y n t h e s i s o f g l y c o s i d e s of aminosugars. I n t h e s e r i e s o f 2-amino-2-deoxy compounds, Bglycosides of

glucosamine h a v e b e e n made u s i n g e i t h e r t h e p e r a c e t y l -

a t e d g l y c o s y l c h l o r i d e w i t h t i n (11) t r i f l a t e as c a t a l y s t , 2 1

or the

p e r a c e t y l a t e d g-phthalimido s u g a r w i t h t i n (IV) c h l o r i d e , 2 2 o r t h e r e a s o n a b l y s t a b l e c y s t a l l i n e b r o m i d e (15) u n d e r Koenigs-Knorr c o n d i t i o n s . The p r o t e c t i n g g r o u p was removed u s i n g c h l o r i n e o r base. 23 F u r t h e r e x a m p l e s o f t h e p r e p a r a t i o n o f g l y c o s i d e s o f 2amino-2-deoxysugars

are g i v e n i n Chapters 9 and 1 9 .

The 3 - a z i d o g l y c o s y l a t i n g a g e n t (16>,made from a m e t h y l a-Dallopyranoside 3 - t r i f l a t e , B-glycoside

has been used i n t h e p r e p a r a t i o n of t h e

A m p h o t e r i c i n B ( C h a p t e r 10) ,24 a n d a n i n d o l e a n a l o g u e

18

Carbohydrate Chemistry

of daunomycin has been made using the glycosyl p-nitrobenzoate. 25 The synthesis of the four diastereomeric methyl b-amino-2,4,6trideoxy-L-hexopyranosides, also required for anthracycline work, is referred to in Chapter 9 .

Considerable attention has been paid to the synthesis of aryl glycosides. One report advocates the use of tert-butyldimethylsilyl derivatives of the phenols together with acylated glycosyl acetates with boron trifluoride as catalyst,26 Another used tetra-0benzoyl-a-D-glucopyranosyl bromide and phenols in the two phase system of aqueous sodium hydroxide and dichloromethane in the presence of a phase transfer catalyst, giving moderate yields of aryl B-D-glucopyranosides. 27 Specific compounds synthesized include 4-0- B-D-glucopyranosylgallic acid 6-sulphate , B-glucosides of dimethyl (hgdroxymethy1)phenyl N-methylcarbarnates (insecticide metabolites) ,29 (thiazolylacetyl) resorcinols ,30 and the glycosides (17) and (18), the former being a powerful inhibitor of ~-glucosidases31 while the latter is related to naturally occurring spermidine conjugates.32 Likewise furanose and pyranose derivatives of the complex phenols 4-methylumbelliferone (made from 1,2-trans-related glycosyl fluorides) ,3 3 xanthotoxol,34 and lY3,5,8-tetrahydroxy-2-methyla n t h r a q ~ i n o n ehave ~ ~ been prepared. Further reports have appeared on standard syntheses of g l u ~ o s y l a t e dand ~ ~ g l ~ c u r o n o s y l a t e dsteroids ~~ and of glucosylated dammarane triterpenes.38'39 The kojic acid derivative (19)~' and d e h y d r o x y r n e t h y l b u l g e c i n A ( 20 1 41 have also been described, the latter a product of using the oxazoline procedure. ~ resulted in the Extension of work on acetal g l y c o ~ i d e s ~ -has synthesis of logamin (21), a key intermediate of biosynthesis, the work depending upon that illustrated in Scheme 7.42 Etoposide ( 2 2 ) ,

**

19

3: Glycosides and Disaccharides

an an'citmour agent, and related 2-amino-2-deoxy-and 3-amino-3-deoxy derivatives and enantiomers have been mad.e using initially 2,3-diO-chloroacetyl-4,6-g-ethylidene-D-glucose as glycosylating agent Pseudo-disaccharides which with catalytic boron trifluoride. 43 ~involve linkage between sugars and pseudo-sugars are referred to in Chapter 18. OH

Me

0

,C22H45


OH

(22)

(26)

Other glycoside syntheses to be reported include those of a-Lrhamnopyranosides of the hydroxyamino acids Sserine and threonine44 derivatives of these compounds and 2-deoxy-a-D-arabino-hexopyranosyl (by the acetylglyxal-NIS method) .45 The cerebrosides (23) and (24) have been made by the trichloroacetimidate method and the former was shown to be the natural product. 46 Compound (25), a cytokinin metabolite, has been obtained via the 4-amino-intermediate which was coupled with 6chloropurine . 47 The glycolipid compound (26) was made using the l,3-dibromo2-hydroxymethylpropane glycoside,48 and the all trans-retinyl 0-Dglucuronide was made by standard methods. 49

Carbohydrate Chemistry

20 1.2

Synthesis of Disaccharides and their Derivatives.-

As before,

reducing disaccharides are treated according to their non-reducing moieties. 2-Pyridyl tetra-2-benzyl-6-D-glucopyranoside has been used to prepare a range of mainly 1,2-*-related disaccharides,50 and ethyl tetra-0-benzoyl- or tetra-g-benzyl-l-thio-6-D-g1ucopyranosidey activated by methyl triflate, give access mainly to 6- and a-linked products, respectively. In this way the 1,3-linked D-glucobioses have been made,51 and the a-isomer has also been made, using tetrabenzyl-a-D-glucopyranosyl bromide, as the der*ivative (27) which can be selectively deprotected for higher saccharide synthesis.52 The effects of pressure on the Helferich glycosylation of methyl 2,4,6-tri-~-acetyl-B-D-glucopyranoside and the 2,3,6substituted isomer have been examined; in both cases increase in

pressure favoured the formation of the @-linked isomers, the 1,4linked isomer changing from an a,@-ratio of 80:20 at atmospheric A related examination of the pressure to 20:80 at 12 kbar.5 3 reaction shown in Scheme 8 showed that increase in pressure could

OAc

OAC

OAo

Me

R e n g e d : i Tr CLOq

Scheme 8

change p o o r selectivity into specificity for the B-linked disacchIt was proposed that at high pressures cyclic 1,2aride. 54 acyloxonium ions were favoured as reaction intermediates over glycosyl carbonium ions. Application of the trichloroacetimidate method has given good yields of 4- and 6-linked glucosyl glucoses and 2-linked glucosylgalactose with good a-selectivity. 55 An efficient preparation of benzyl glycosides of lactose and 56 cellobiose from the disaccharide peracetates has been reported, and the eight possible monodeoxy analogues of methyl 6-maltoside

3: Glycosides and Disaccharides

21

and the 6,6'-and 1,2-dideoxy compounds have been tested as substrates for amyloglucosidase. Hydroxy groups were found to be required at C-3, 4' and 6' for activity.57 A synthesis of methyl 6-~-a-D-glucopyranosyl-a-D-glucopyranoside with good a-glucosylating activity resulting from the use of 2,3,4tri-~-benzyl-6-~-trirnethylsilyl-a-D-glucosyl bromide [which was assumed to react by way of ion (2811 has been described.58 Treatment of a 90% glucose solution with the 6-glucosidase from almond can be made to yield 40% of mixed B-linked D-glucobioses.59 Disaccharides having D-glucose linked to the fallowing other sugars have been reported: 2-acetylamino-2-deoxy-D-mannuronic acid (a-l+ 4),60 D-galactose (a-l* 6 and B - 1 + 6) ,51 formylmethyl 2,3-di0-methyl-a-L-rhamnopyranoside ( 3,6-di-g-methyl-D-glucose 6-1 -+ 4 62 linked),61 and the corresponding benzyl and ally1 glycosides (these compounds required for immunological work). Other disaccharides having D-glucose bonded to a 6-amino-2,3,6-trideoxysugar and D-ribose of a nucleoside are referred to in Chapter 19.

2,3,~-Tri-~-acetyl-6-~-tert-butyldipheny1si1y1-a-D-ga1actosy1 chloride has been used in the synthesis of B - 1 3 6 linked D-galactose di-, tri- and oligosaccharides,63 and methyl 2,3,4,6-tetra-Q-acetyl1-thio-B-D-galactopyranoside used with nitrosyl tetrafluoroborate also gives good yields of B-linked disaccharides.64 On the other hand, the trichloroacetimidate method has given high yields of 4and 6-linked D-galactosylglucose and 2-linked D-galactosylgalactose with good a - ~ e l e c t i v i t y . ~ The ~ nature of the products formed by enzymic a-D-galactosyl transfer to D-galactose is dependent on glycosylation of the acceptor and its anomeric configuration. Glycosylation inhibits formation of l + 6 linked products.65 The 6- and 2I-Q-methyl derivatives of N-acetyllactosamine have been prepared for biochemical studies ,66 '67-and various lactosylceramides have been made by the trichloroacetimidate route.68 6'-(~)-2H-Methyl lactoside has been synthesized from the known specifically labelled compound (29) for use in enzymic syntheses of trisaccharides.69

22

Carbohydrate Chemistry

A route to 1,6-anhydro lactose, maltose and cellobiose by use of g l y c o s y l sulphones is reported in Chapter 5. In the D-mannopyranosyl disaccharide set of compounds a novel route to mainly a-linked derivatives is illustrated in Scheme 9,70 and of the D-mannobioses the a-l-+6-linked compound has been prepared as the 6-phosphate ester of the a-methyl-9-methyl nonanmte By use of 4-uloside intermediates methyl 2-g-a-Dglycoside. 71

Reagent

L,TMSOT~

Scheme

9

mannopyranosyl-a-D-talopyranoside

and methyl 2-~-a-D-talopyranosyla-D-talopyranoside have been prepared, 72 as have the 3-linked isomers.73 In interesting use of sulphenate esters in a general synthetic route to 2-de~xy-D-arabino-hexopyranosyl disaccharides is illustrated in Scheme 10. The products illustrated were desulphurized, yields were >80$ and @:a-ratios varied from 1.5-4:l. 74

In the reaction of 3,4-di-g-acetyl-1,2-O-endo-cyanoethylidene6-deoxy-a-D-glucopyranose with tetra-g-acetyl-3-G-triphenylmethyl6-D-glucose in the presence of tritylium perchlorate 14 kbar of pressure resulted in the formation of the @-linked product exclusively.7 5 3-~-Benzyl-6-deoxy-D-glucose has been used as the source of both components required in the synthesis of the disaccharide 2-2-(3-0-acetyl-6-deoxy a-D-glucopyranosyl)-4-g-acetyl6-deoxy-D-glucose and the antitumor terpenoid compound phyllanthostatin of which it is a component.76 The disaccharide is linked to a carboxylic acid in the natural product; synthetically this bond can be made by the Mitsunobu procedure .77'78 Disaccharides with a-L-rhamnopyranose linked to the 4-position of D-glucuronic acid7' and separately to the 3,4 and 6 positions of 2-amino-2-deoxy-D-glucose have been reported,8o as have compounds

3: Glycosides and Disaccharides

23

with B-L-rhamnose bonded to the 2-positions of methyl 6-D-glucopyranoside and methyl a-L-arabinopyranoside” and to the ?-position of ( 3 ’ , 4 ’ - d i h y d r o x y p h e n y l ) - 2 - e t h y l - B - 0 - g l u c o p y r a n o s i d e . In t h i s case the rhamnoside carried methyl groups at 0-3 and 0-4 and the p r o d u c t was required for comparison with a plant component.82 The preparations of the disaccharides having 6-deoxy-4-g-methyl-Dglucose linked a- and 8- to 0-4 and a- to 0-3 of 2,6-di-Q-methyl-Dmannose have been reported, the B - l + 4 compound being the disacchThe g-iodosuccininide approach aride EF moiety of flambamycin. 83 has been used in the synthesis of disaccharide derivative (30) and its linking to the aglycone of Avermectin Ala in the total synthesis of the compound. 84

OM e

OMe

(30)

Preparation of the disaccharides having L-iduronic acid a- and B-1-+3 linked to methyl 2-acetylamino-2-deoxy-~-~-galactoside 4sulphate has been reported.85 Considerable attention has been given to the synthesis of disaccharides with ulosonic acid non-reducing compounds - particuacid (KDO). The a-1+4 linked larly 3-deoxy-D-manno-octulosoiiic disaccharide with an a-ally1 aglycone was made as a means of incorporating KDO into polyacrylamide copolymers,86 but particular attention has been paid t o the dimer having KDO a-l+6 linked to 2amino-2-deoxy-D-glucose 4-phosphate in connection with studies of lipid A. Several analogues, some with anti-tumour activity, and having long linear substituents at E-2 and 0-3, have been reported 9 87-90 and a method of access to the dimer based on the use of a glycosyl fluoride has been described.l2 Disaccharides having aor B- bonded l-acetylnemaminic acid as non-reducing units have been produced by a new method depending on the use of the a-glycosyl fluorides having a cis- or trans - phenylseleno group at C - 3 . These were obtained from the well known 2-ene. l7 A related method, also based on this ene, gives 6-linked disaccharides by way of the 2,3-epoxide.19 The a-2+9 disialic acid has been made,91 as have compounds (31)-(34) with N-acetylneuraminic acid a- and 6-2+3 linked to D-galactose . 9 2 In the area of aminodeoxy-containing disaccharides main attention has been given to dimers of 2-amino-2-deoxy-D-glucose.

Carbohydrate Chemistry

24 H $ CO C 23H47 u0+C13H27

OH

(31) R = ~ r Neu Ac ( 2 + 3)p-Gal.p

(32) R - K -

11

(33) R = p (34)

R ap-

01

o(-

41

p-

It

cx-

It

-

&q &AEk

N3

(3 5)

W i t h B-1-+4

l i n k e d compounds two r e p o r t s h a v e d e s c r i b e d p r e p a r a t i o n s of t h e b a s i c u n i t o f c e l l wall p e p t i d o g l y c a n s o f b a c t e r i a , i . e . , t h e d i m e r h a v i n g a muramic a c i d ( 3 - l a c t y l e t h e r ) a t t h e r e d u c i n g e n d , 9 3 y 9 4 a n d one d e s c r i b e s a n analogue w i t h a d i p e p t i d e b o n d e d a t

0-3.95 A s e t o f d i s a c c h a r i d e s w i t h muramic a c i d a t t h e r e d u c i n g end have a l s o been d e s c r i b e d . 9 4 I n t e r e s t i n B-1+6 l i n k e d compounds has f o c u s s e d on b a c t e r i a l l i p i d A h a v i n g p h o s p h a t e g r o u p s a t 0-1 a n d 0-4' a n d f a t t y a c i d g r o u p s a t 0-3 a n d 0-3' .96-98 A b a s i c r o u t e to compounds o f t h i s g r o u p has b e e n d e f i n e d g 9 a n d a compound w i t h muramic a c i d a t t h e y e d u c i n g p o s i t i o n w i t h a bonded d i p e p t i d e a t t a c h e d has b e e n r e p o r t e d . 100 4,6-Dideoxy-4-formamido-D-mannose h a s b e e n d i m e r i z e d by a-1-+2 l i n k i n g , a n d t h e r e l a t e d t r i m e r has b e e n made i n t h e c c u r s e o f An e x t e n s i o n u s i n g t h e t h i o g l y c o s i d e ( 3 5 ) i m m u n o l o g i c a l work. g a v e d i - to p e n t a - s a c c h a r i d e s o f t h e s e r i e s a n d a l s o a n a l o g u e s 102 h a v i n g a-1-+3 l i n k a g e s . I n t h e p e n t o s e s e r i e s 2-~-@-D-xylopyranosyl-D-glucose has b e e n bonded t o a d i t e r p e n e t o p r o d u c e t h e sweet b a i y u n ~ s i d e , a~n~d ~t h e 104 6 - @ - l i n k e d i s o m e r has b e e n made as i t s B - p - a l - l y l p h e n y l g l y c o s i d e . S e v e r a l d i s a c c h a r i d e s h a v i n g L - a r a b i n o f u r a n o s e l i n k e d t o 0-4 o f D - g l u c o s e , L - a r a b i n o s e a n d D-xylose h a v e b e e n made u s i n g t h e l Y 2 - c y a n o e t h y l i d e n e d e r i v a t i v e a n d 0-4 t r i t y l e t h e r s , and 6 - D - r i b o f u r a n o s e l i n k e d B- t o 0-7 o f KDO B - a l l y 1 g l y c o s i d e h a s b e e n 86 reported.

1 . 3 0 - G l y c o s i d e s I s o l a t e d from N a t u r a l P r o d u c t s .- A s a l w a y s , o n l y compounds h a v i n g n o t a b l e f e a t u r e s i n t h e c a r b o h y d r a t e p o r t i o n s a r e recorded. H e l i c i d o l , a compound i s o l a t e d f r o m t h e s e e d s o f H e l i c i a e r r a t i c a , has b e e n c h a r a c t e r i z e d a s p-hydroxymethyl B-D-allopyranThe hex-1-enosid-3-uloses ( 3 6 ) and ( 3 7 ) have a l s o been oside. i s o l a t e d from a p l a n t s o u r c e a n d t h e t o x i c p r i n c i p l e from U r g i n e a r u b e l l a has b e e n f o u n d t o c o n t a i n t h e h e x o s i d - 3 - u l o s e a c e t a l 1 08 structure (38).

25

3: Glycosides and Disaccharides HO

(36) R' = s e s c p t e q e n e , R2= Prrgeloyt (37)

R'=

7)

, R*=

senecioyL H

(3 8)

S t e r o i d a l g l y c o s i d e s from a g o r g o n i a n c o n t a i n 3-2-8-D-arabinofuranosyl-8-D-glucose and t h e analogue w i t h an a c e t y l e s t e r group a t C-2 o f t h e p e n t o s e u n i t . They i n h i b i t c e l l d i v i s i o n o f s e a u r c h i n e g g s . 109

1 . 4 H y d r o l y s i s and Other Reactions and F e a t u r e s . - The e f f e c t s o f s u b s t i t u e n t s i n t h e a r o m a t i c r i n g s o f 8 - D - g l u c o p y r a n o s i d e s on t h e i r r a t e s a n d mechanisms o f h y d r o l y s i s i n c o n c e n t r a t e d p o t a s s i u m as h a v e t h e r e a c t i o n s o f h y d r o x i d e ( 1 2 . 7 5 M) h a v e b e e n s t u d i e d , some d i s a c c h a r i d e s w i t h a l k a l i n e h y d r o g e n p e r o x i d e . F i v e d i f f e r e n t p a t h s w e r e i d e n t i f i e d , i n c l u d i n g a newly p r o p o s e d p e r o x y r a d i c a l 111 mechanism which i s more r a p i d t h a n t h e o t h e r s . I n v e r t a s e - c a t a l y s e d h y d r o l y s i s of sucrose can occur t o t h e e x t e n t o f 9 9 % i n 1 min w i t h r e t e n t i o n o f c o n f i g u r a t i o n a t b o t h 112 anomeric c e n t r e s . A s p e c i f i c method o f d e p r o t e c t i n g 2 - c h l o r o e t h y l g l y c o s i d e s ( a n d p r e s u m a b l y e t h e r s ) i n v o l v e s h e a t i n g w i t h sodium b e n z e n e s u l p h i n a t e a n d p o t a s s i u m i o d i d e i n DMF. The r e a c t i o n s p r o c e e d by way o f p h e n y l s u l p h o n e s which t h e n u n d e r g o @ - e l i m i n a t i o n o f t h e c a r b o h y d r a t e portions. A s p e c i f i c method o f c l e a v i n g n a t u r a l p r o d u c t s c o n t a i n i n g a component which i s a n a l l y 1 g l y c o s i d e i n v o l v i n g a l l y l i c bromination i s d e s c r i b e d i n Chapter 1 9 . T h e u n u s u a l r e a c t i o n i l l u s t r a t e d i n Scheme 11 i s p r o p o s e d t o involve t i n - c a t a l y s e d anomerization followed by c h e l a t i o n of t i n s p e c i e s t o 0-1 a n d 0-2 t h u s a c t i v a t i n g t h e 2 - b e n z y l e t h e r t o g i v e a 2 - t r i c h l o r o s t a n n y l i n t e r m e d i a t e a n d l e a d i n g t o t h e f i r s t example o f

% ~ ~ ~ ~ e ri r, t~ sn: ~

~ q ;Hi L~ , O

Scheme 11

s e l e c t i v e debenzylation a t a secondary p o s i t i o n .

See Chapter 5 f o r

Carbohydrate Chemistry

26

e x a m p l e s o f i t s a p p l i c a t i o n i n t h e p r e p a r a t i o n of 2 - s u b s t i t u t e d D-arabinose

derivatives. The s e l e c t i v e a c e t o l y s i s of methyl 2,3,4,6-tetra-O-benzyl-u-D-~iannopyranoside i s also referred t o i n

Chapter 5 . M e t h y l g l y c o s i d e s , t r e a t e d w i t h b o r o n t r i c h l o r i d e a t -78' i n dichloromethane, a f f o r d t h e corresponding g l y c o s y l chlorides i n a r e a c t i o n which i s c o m p a t i b l e irlith t h e p r e s e n c e o f b e n z y l e t h e r s , a c e t y l groups and o t h e r glycosyl l i n k a g e s . 'I5 permethyl 2-deoxy-derivatives

On t h e o t h e r h a r d ,

give high y i e l d s of a c y c l i c products

when t r e a t e d w i t h d i r n e t h y l b o r o n b r o m i d e f o l l o w e d by a n u c l e o p h i l e i n b a s i c c o n d i t i o n s (Scheme 1 2 ) . The r e s u l t s o b t a i n e d from s e v e r a l

g l y c o s i d e s were r a t i o n a l i z e d on t h e b a s i s o f t h e o p e r a t i o n o f t h e a n o m e r i c and e x o - a n o m e r i c

effects.

116

A t h e o r e t i c a l s t u d y h a s b e e n made o f t h e s t e r e o c h e m i s t r y o f

m e t h y l a- a n d 6 - D - g l u c o p y r a n o s i d e

2

i n various solvents.

117

S-Glvcosides

S u g a r p e r a c e t a t e s t r e a t e d w i t h methylthiotrimethylsilane a n d b o r o n t r i f l u o r i d e give the lY2-trans-related 1-thioglycosides i n a high y i e l d i n g method w h i c h a v o i d s s m e l l ,'I8 a n d D-xylose w i t h t e r t - b u t y l t h i o l

and r e a c t i o n o f D-glucose

a f f o r d s anomeric m i x t u r e s o f t h e

tert-butyl

1-thioglycopyranosides. Acetylated aldehydo-derivatives gave t h e c o r r e s p o n d i n g d i t h i o a c e t a l s . 119 The a r y l t h i o g l y c o s i d e s ( 3 9 ) and ( 4 0 ) h a v e b e e n made, t h e f o r m e r as a p o t e n t i a l s u b s t r a t e f o r a g l u c u r o n i d a s e 1 2 ' a n d t h e l a t t e r by a n a d d i t i o n t o t r i - ~ - a c e t y l - D - g l u c a l i n t h e p r e s e n c e of

(39)

p-toluenesul.phonic a c i d .

No a l l y l i c r e a r r a n g e m e n t was o b s e r v e d .

121

27

3: Glycosides and Disaccharides

Cinnamyl 1-thioglycosides have been made from 1-thiourea analogues by use of 2-bromostyrene in a study of inhibition of 122 delayed hypersensitivity reaction.

3

C-Glycosides

3 . 1 Pyranoid Compounds.- Two reports, both involving the heteroDiels Alder reaction, have described the synthesis of racemic C-glycosides. The first (Scheme 13) develops a route to aryl glycosides with some optical induction obtained when R was chi~al,'*~ and the second (Scheme 14) an approach to lyxopyranosyl 124 derivatives.

c-

An extensive range of methods involving anomeric substitution reactions have been applied, several utilising glycosyl lithium intermediates, and Sinay and his coworkers have described fully their pioneering work in this area ( c .f., Vol. 19, p . 31 and 161) Such nucleophilic intermediates take part in conjugate addition processes, a- and B-bonded precursors giving a- and B-2-glycosides C-Glycosides of KDO are a l s o readily made by way (Scheme 15). -

gh Sn6ug

5nO

)I-LL

Reageds

L,

GULL ,u,Gd3r Me,S , h,0

0 ,LV, BF3

S c h e m e 15

0

Carbohydrate Chemistry

28

of a n i o n i c i n t e r m e d i a t e s (Scheme 161, t h e B - p r o d u c t s p r e d o m i n a t i n g t h e X-Ray d i f f r a c t i o n a n a l y s i s o f compound

w i t h R=CN,CH20H,COMe;

R q e d s : i, Ha-P&/C ; i i , MeOL;iii,Me2CO-Hi;W,LDA;v,Rx

S c h e m e 16

( 4 1 ) was c a r r i e d o u t t o p r o v i d e a r e f e r e n c e compound for a n o m e r i c as si gnment .127

O t h e r methods h a v e depended upon n u c l e o p h i l i c a t t a c k a t t h e a n o m e r i c c e n t r e ; t h e s e i n c l u d e r e a c t i o n o f tetra-2-acetyl-a-D-glucop y r a n o s y l c h l o r i d e w i t h l i t h i u m d i a r y 1 c u p r a t e s t o g i v e B-cglycosides a n d r e a c t i o n o f tetra-0-benzyl-a-D-glucopyranosyl c h l o r i d e w i t h s i l y l e n o l e t h e r s a n d s i l v e r t r i f l a t e t o g i v e good I n r e l a t e d work y i e l d s o f m a i n l y 2 - l i n k e d compounds e . g . , ( 4 2 ) . a o n e - p o t r o u t e f r o m 2,3,4,6-tetra-Q-benzyl-D-glucose p r o c e e d e d by way o f t h e 8 - t r i f l u o r o a c e t a t e which was t r e a t e d w i t h s i l y l e n o l e t h e r s or a l l y l t r i m e t h y l s i l a n e t o g i v e B - p r o d u c t s , o r w i t h a r o m a t i c h y d r o c a r b o n s a n d BF3 t o g i v e m a i n l y a - d e r i v a t i v e s . 130 An i m p r o v e d p r o c e d u r e f o r making b o t h p y r a n o s y l a n d f u r a n o s y l cyanides involves the use of t h e g l y c o s y l a c e t a t e s and t r i m e t h y l s i l y l c y a n i d e a n d b o r o n t r i f l u o r i d e , 1 3 ' a n d a f u r t h e r method i n v o l v e s t h e t r e a t m e n t o f compounds w i t h t h e n i t r o m e t h y l a n o m e r i c The method i s p a r t i c u l a r l y s u i t e d f o r g i v i n g s u b s t i t u e n t with PC15. 1,2-&-related g l y c o s y l c y a n i d e s . 132 T r i c h l o r o a c e t i m i d a t e s may a l s o b e u s e d as i n d i c a t e d i n Scheme 17; C - g l y c o s y l a t e d t h i o p h e n e a n d i n d o l e compounds may a l s o b e made b y t h i s a p p r o a c h . 133 An e x t e n s i o n o f t h i s method h a s b e e n u s e d

i n t r a m o l e c u l a r l y t o g i v e t h e b e r g e n i n d e r i v a t i v e ( 4 3 ) . 134 S i l y l a t e d glycosides treated w i t h a l l y l t r i m e t h y l s i l a n e and t r i m e t h y l s i l y l t r i f l a t e g i v e good y i e l d s o f a l l y 1 C - g l y c o s i d e s i n t h e f u r a n o i d and p y r a noid and a l d o s i d e and k e t o s i d e s e r i e s . With g l u c o s i d e s a n d r i b o f u r a n o s i d e s 1,2-*-related products can be

29

3: Glycosides and Disaccharides

R

q

h

:L,

ZnC4-Etp0; ii, McO,ccrCCOzMe

i

iii, T i C L 4 ; iv, Et3N

Scheme 17

Cop Me

o b t a i n e d w i t h h i g h s e l e c t i v i t y . Use o f t r i e t h y l s i l a n e l e a d s t o a-Mannopyranosides a r e o b t a i n good y i e l d s o f a n h y d r o a l d i t o l s . 135 e d w i t h good s e l e c t i v i t y . 1 3 6

Suitably protected phenylthio glycosides t r e a t e d with dialkyl Both z i n c s i n d i - i o d o m e t h a n e o f f e r a new r o u t e t o C - g l y c o s i d e s . a- a n d B-D-glucopyranose compounds g a v e p r o d u c t s w i t h a 3:l a : B P h e n y l t h i o g l y c o s i d e s c a n b e u s e d to g i v e m a l o n i c a c i d r a t i o . 137 C - g l y c o s i d e s (Scheme 18). 138

R e 4 g h : i , N2C(COZEt)2-

Rh (OAC.)~; G , R o n y NL

S c h e m e 18

S e v e r a l approaches t o C-glycosides have used alkenes produced from a l d o s e s by W i t t i g or r e l a t e d p r o c e d u r e s . The a l k e n e (44) was o b t a i n e d from 2,3,4,6-tetra-~-benzyl-D-mannose, g i v i n g m a i n l y t h e B-product (45) on i o d o c y c l i z a t i o n . T h e method was a l s o a p p l i e d i n t h e f u r a n o i d s e r i e s and a g a i n gave 1 , Z - t r a n s - r e l a t e d - p r o d u c t s . 139 t 140 Both anomers of ( 4 6 ) c a n b e made by u s e o f (EtO)2POCHC02Et Na . W i t t i g p r o c e d u r e s have been used t o o b t a i n e q u a l p r o p o r t i o n s o f compounds ( 47) ,lLi1a n d t h e g l u c o s a m i n e d e r i v a t i v e s (48), which a r e i n h i b i t o r s o f human B-D-hexosaminidase,have b e e n made s i m i l a r l y . 1 4 2 T h e p r e p a r a t i o n of a n o j i r i m y c i n 5 - g l y c o s i d i c d i s a c c h a r i d e , w h i c h i s a p o t e n t a - g l u c o s i d a s e i n h i b i t o r , i s o u t l i n e d i n Scheme 1 9 . 143

30

Carbohydrate Chemistry

(44)

(45) C02Et

OH

(47)

S e v e r a l a d d i t i o n a l reports h a v e a p p e a r e d on t h e u s e o f u n s a t u r a t e d compounds i n t h e s y n t h e s i s of-C - g l y c o s i d e s .

The a l l y l i c

rearrangement of g l y c a l d e r i v a t i v e s continues t o r e c e i v e a t t e n t i o n . Tri-2-acetyl-D-glucal,

t r e a t e d w i t h a l l y l t r i m e t h y l s i l a n e , 1,2-

bis(trimethylsily1)acetylene

and f u r a n i n t h e p r e s e n c e of L e w i s a c i d

c a t a l y s t s , g i v e s compounds (49)

-

(51) r e s p e c t i v e l y ; (51) was

o b t a i n e d w i t h a n e q u a l p r o p o r t i o n o f t h e j-somer (52), which i s a n

u n u s u a l t y p e o f p r o d u c t from t h i s k i n d o f r e a c t i o n and was presumab l y formed from t h e 3 - s u b s t i t u t e d

g l y c a l by a p r o t o t r o p i c

144 rearrangement. Scheme 2 0 i l l u s t r a t e s t h e d e p e n d e n c e upon t h e n a t u r e o f t h e r e a g e n t s of t h e p r o d u c t s f o u n d u s i n g d i f f e r e n t b u t - 2 - e n g l s i l a n e s i n t h i s t y p e o f r e a c t i o n . 145 e t h e r s , 146 reagents

A r e l a t e d a p p r o a c h u t i l i z e s homoenol

and a n o t h e r s u b s t i t u t i o n r e a c t i o n u s e s o r g a n o a l u m i n i u m (Scheme 2 1 ) .

31

3: Clycosides and Disaccharides

;L

+

@ AAcO (&

AcO

Me

Me

R-ehts,

L,

BF3 t R S L R ~

R = Me-

5 i Me3

e S i M e 3

R=

3 1

: -

1

1

.

7

3

Me

R=

+SLDuC Me

Ph,

Scheme 20 -____

A

c-o

~ Me c "

"

The f i r s t C l a i s e n r e a r r a n g e m e n t o f t h e p a i r shown i n Scheme 2 2 i s much t h e f a s t e r , and t h e p r o c e s s e s c a n t h e r e f c r e b e u s e d t o make 2-enes

or 3-enes i n t h i s s e r i e s .

The r a t e d i f f e r e n c e , which was

___f

R = SL Bu'Me,

Scheme 22

n o t o b s e r v a b l e w i t h c y c l o h e x e n e d e r i v a t i v e s , was a s c r i b e d t o t h e w e a k e n i n g o f t h e C-3-0

bond by a " v i n y l o g o u s a n o m e r i c e f f e c t " .

A

t h o r o u g h d i s c u s s i o n o f s t e r i c a n d s t e r e o e l e c t r o n i c e f f e c t s was

148

given. 2,3-Unsaturated C-glycosides

c a n b e made b y d i r e c t s u b s t i t u t -

ions applied t o o t h e r 2,3-unsaturated

compounds.

Thus, p h e n y l

g l y c o s i d e s t r e a t e d w i t h e t h y l n i t r o a c e t a t e , t r i p h e n y l p h o s p h i n e and

a Pd(0) c a t a l y s t , g i v e good y i e l d s o f p r o d u c t s h a v i n g t h e CH(N02)C02Et substituent, with r e t e n t i o n o f a n o m e r i c c o n f i g u r a t i o n . 149 S i m i l a r l y , 2-acetyl-1-thio-compounds w i t h a r y l z i n c c h l o r i d e s a n d Pd(PPh l 4 g i v e a r y l C - g l y c o s l d e s , b u t w i t h i n v e r s i o n o f c o n f i g u r a t ion.l5$ An a p p r o a c h t o a r y l C - g l y c o s i d e s by way o f p h e n y l 1 - t h i o 2 , 3 - u n s a t u r a t e d g l y c o s i d e s and d e r i v e d C - 1

l i t h i o intermediates is

noted i n Chapter 13. Two r e p o r t s h a v e u t i l i z e d 3 - u l o s e a n a l o g u e s o f g l y c a l s .

I n the

32

Carbohydrate Chemistry

f i r s t , d i p h e n y l c o p p e r complexes were u s e d t o o b t a i n p r o d u c t s s u c h

as ( 5 3 ) ( f o l l o w i n g a c e t y l a t i o n ) ,15' and i n t h e second, e n o l s i l y l e t h e r s a n d T i (IV) c a t a l y s t s a f f o r d e d t h e r e a r r a n g e d p r o d u c t s ( 5 4 ) .152 A f u r t h e r approach t o 2-giycosides v i a 2-phenylthiogly-

c a l s i s i l l u s t r a t e d i n Scheme 2 3 . 153

Glycosyl r a d i c a l s added t o e l e c t r o n - d e f i c i e n t a l k e n e s a f f o r d access t o C-glycosides,

examples having been g i v e n i n a review of

" R a d i c a l R e a c t i o n s i n O r g a n i c S y n t h e s i s " . 154

Compounds (55)-(57)

were amongst compounds r e p o r t e d as h a v i n g b e e n made by a d d i t i o n o f

& ;?I-,. &' CHeOAc

CHZOBn

A d

01-10

OAc

(55)

NEt

0

(56)

OBn

CN

(57)

t h e t e t r a-2- a c F? t y 1-D-g luc o s y 1 r a d i c a1 to b u t e none l5 a n d N-e t h y 1s u c c i n i m i d e , 155 a n d a d d i t i o n o f a h e p t - 2 - u l o s y l r a d i c a l to An e x t e n s i o n o f t h i s a p p r o a c h h a s a l l o w e d c h a i n a c r y l o n i t r i l e . 156 e x t e n s i o n from C-1 a n d from C-5 o f a D - x y l o p y r a n o s e r i n g t o g i v e a c c e s s t o a 4,8-anhydroundecanose (Scheme 2 4 ) .

d e r i v a t i v e w i t h good s e l e c t i v i t y

A key s t e p was t h e p r o d u c t i o n o f a s i n g l e b r o m i d e ( 5 8 ) CN

CN

OAc

S c h e m e 24

3: Glycosides and Disaccharides

33

by p h o t o b r o m i n a t i o n o f t h e e p i m e r i c n i t r i l e s ( 5 9 ) w h i c h c a n b e a c c o u n t e d f o r by c o n f o r m a t i o n a l c o n t r o l 1 A H n . m . r . s t u d y o f a s e r i e s o f a- a n d B-D-C-glucopyranosides h a s shown t h a t t h e p r e f e r r e d r o t a m e r s t a t e s a b o u t t h e " g l y c o s i d i c " bond a r e ( 6 0 ) a n d (611, i . e . , by 2 - g l y c o s i d e s . 158

t h e y are analogous t o t h o s e favoured

R e l a t e d s t u d i e s on t h e p r e f e r r e d c o n f o r m a t i o n s

H+IR H

of 2 - l i n k e d a n a l o g u e s o f t h e 1,4-cx, 1,4-B , 1,6-a a n d 1,643 l i n k e d a r e r e f e r r e d t o i n C h a p t e r 2 1 . The s y n t h e t i c a p p r o a c h t o t h e f i r s t two of t h e s e i s o u t l i n e d i n Scheme 25.159

methyl D-glucobioses

Pn +

BnO f 0

0 Bn

+PPh3 I-

OH

OH

+

a(-

+

both 4 - C - m a n n o s y l -

Lmked fiorner D - 9 LUCOsLdC

Scheme 25

D e g r a d a t i o n o f c a r m i n i c a c i d (62), t h e p r i n c i p a l component o f c o c h i n e a l , w i t h 6 0 % s u l p h u r i c a c i d g a v e as a mEin p r o d u c t t h e anthrafuradione (63).

A possible route involving a retroaldol s t e p

i s i n d i c a t e d i n Scheme 2 6 .

160

CH20H

CH2OY

+.

&--@p

HO

HO

Mey' f D-erythrose 0

I

ace$ / OH

\ OH

S c h e m e 26

3.2

F u r a n o i d Compounds.-

0

(631

Reaction of s u b s t i t u t e d D-ribofuranosyl

f l u o r i d e s w i t h s i l y l e n o l e t h e r s and a l l y 1 t r i m e t h y l s i l a n e g i v e s m a i n l y a - 5 - g l y c o s i d e s .I6' B-D-ribosyl

S i m i l a r r e a c t i o n o f 2 ,3 , 5 - t r i - O --b e n z y l -

a c e t a t e w i t h v a r i o u s s i l y l a t e d n u c l e o p h i l e s also affords

34

Carbohydrate Chemistry

a - l i n k e d p r o d u c t s . '62

I n t h e a r e a o f 2-deoxy-D-erythro-pentose

compoundsJ t h e g l y c o s y l a c e t a t e (64) g i v e s a c c e s s to 6 - g - g l y c o s i d e s

as i n d i c a t e d i n Scheme 2 7 . 163

A f u l l p a p e r on t h e i n t r a m o l e c u l a r

OCH2CH2$ Me

Nzz

(64) R-&

L,,

OCH~CH~SO~M~

O

-

TMSOV

,u.,o x & ~ o n

Scheme 27 C-arylation

of benzylated pentofuranosyl a c e t a t e s has appeared.

V a r i o u s o t n e r means o f o b t a i n i n g f u r a n o s y l C - g l y c o s i d e s

16 4

have

been described. The f r u c t o f u r a n o s i d e (65) a f f o r d e d t h e g - a l l y 1 compound ( 6 5 ) f r o m w h i c h a- a n d 6 - D - f r u c t o f u r a n o s y l C--glycosides w e r e p r o d u c e d ; 165

compound (67), o n t r e a t m e n t w i t h N - b r o m o s u c c i n i -

m i d e , p a v e t h e D r o d u c t o f 0-5 p a r t i c i p a t i o n ( 6 8 ) ; 166- and. t h e 2-2-

I

(67) ODn

t r i f l a t e (69), t r e a t e d w i t h s o d i u m a z i d e , g a v e t h e p r o d u c t o f r i n g c o n t r a c t i o n (TO), w h i c h o n r e d u c t i o n a f f o r d e d t h e a l d e h y d e (71) (Scheme 2 8 ) . L i k e w i s e , compound ( 7 2 ) g a v e ( 7 3 ) i n h i g h y i e l d o n t r e a t m e n t w i t h s o d i u m a z i d e . 167

35

3: Glycosides and Disaccharides

The alkene (74), produced by Wittig chemistry from 2,3,5-trireacts with electrophiles to give the 6-cglycosides (75)168 and the phosphonate (76)169 from which the Darabinose phosphonate isostere (77) of D-arabinose lY5-diphosphate was made. 0-benzyl-D-arabinose,

Reaction of 2,3-Q-isopropylidene-D-ribose with Wittig reagents gives mainly B-products under kinetic control and a-products 141 following equilibration with base (Scheme 2?).

CN L,ii

f

(J-

/

0

.

0

x

2,3:5,6-Di-~-isopropylidene-D-mannono-y-lactone treated with tris(dimethy1amino)phosphine in carbon tetrachloride gave the g dichloromethylene product which on hydrogenation resulted in the In related work 2,3-Q-isopro1-deoxyheptitol derivative (78).I7O pylidene-5-~-tert-butyldimethylsilyl-D-ribono-y-lactone gave the a-products (79) on treatment with lithiumaryls, and an extension of this methodology gave the dimer (80) and hence, by linking C-5 to

0

xo(79)

C-5'

by way of a diamide bridge, a water-soluble receptor for hydrophobic groups. 171 Synthesis of C-glycosides related to ravidomycin and related antibiotics by palladium - mediated coupling of furanoid g l y c a l s is illustrated in Scheme 30. 172

36

Carbohydrate Chemistry

ReagenLs:

L,

OH

PCL(OAC)~;ii, F-;iii, NaBH4

+c-3'epimw

S c h e m e 30

The known 2-C-(Z,3,5-tri-~-benzoyl-B-D-ribofuranosyl)furan has been converted into corresponding glycosyl-!-heterocycles which are C-nucleoside analogues ,173y174 and the related compounds (81) and

(821, prepared from D-glucose and 6-dicarbonyl derivatives, have been used to obtain (83)175 and (84),

&?!; OH

OH

(81) Ri= (82) R'= Ri= CO.Me, CO.Me, CH20H,R2= R2= R2=Me Me Ph (82) R'= CH20H, R2= Ph

A c-glyco-

respectively.

Ph

13cH

a N

0

/

0

(84)

X

sylnaphthalene has been prepared as outlined in Scheme 31.177 Other furanosylheterocycles are noted in Chapter 9.

References H.Kunz, Angew. Chem., Int. Ed. Engl., 1987, 26, 294. T.Inazu, Noguchi Kenkyusho Jiho, 1985, 21 (Chem. Abstr., 1987, 107,78 159). F.Nicotra, L.Panza, F-Ronchetti, G.RUSSO, and L.Toma, J. Chem. Sot.-, Perkin Trans. I, 1987, 1319. A.de Raadt and R.J.Ferrier, J. Chem. SOC., Chem. Commun., 1987, 1009. L.F.Tietze, R.Fischer, H.J.Guder, A.Goerlach, M.Neumann, and T.Krach, Carbohydr. Res., 1987, 164,177. L.F.Tietze, R.Fischer, H.-J.Guder, and M.Neumann, Liebigs Ann. Chem., 1987, 847. J.Lehmann and L.Ziser, Carbohydr. Res., 1987, 169, 53.

37

3: Glycosides and Disaccharides 8

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40

K.Weinges, S.Haremsa, and W.Maurer, Carbohydr. Res., 1987, 164,453. W.V.Dahlhoff, Synthesis, 1987, 366 (Chem. Abstr., 1987, 107,237 153) A.Lubineau and Y.Queneau, J. Orq. Chem., 1987, 52, 1001. A.Saroli and A.Doutheau, Tetrahedron Lett., 1987, 28, 5501. M.Imoto, N.Kusunose, Y.Matsuura, S.Kusumoto, and T.Shiba, Tetrahedron Lett., 1987, 28, 6277. V.Eschenfelder and R.Brossmer, Carbohydr. Res. , 1987, 162, 294. R.Roy, C.A.Laferri&e, A.Gamian, and H.J.Jenninqs, J. Carbohydr. Chem., 1987, 6, 161. M.Kiso, A.Nakamura, and A.Hasegawa, J. Carbohydr. Chem., 1987, 6, 411. K.Okamoto, T.Kondo, and T.Goto, Tetrahedron, 1987, 43, 5919. Y.Ito and T.Ogawa, Tetrahedron Lett., 1987, 28, 6221. K.Okamoto, T.Kondo, and T.Goto, Tetrahedron, 1987, 43, 5909. K.Okamoto, T.Kondo, and T.Goto, Bull. Chem. Soc. Jpn., 1987, 60, 637. S.Sato, S.Fujita, K.Furuhata, H.Oqura, S.Yoshimura, M.Itoh, and Y-Shitori, Chem. Pharm. Bull., 1987, 35, 4043. A.Lubineau, J.Le Gallic, and A.Malleron, Tetrahedron Lett., 1987, 28, 5041. M.T.Campos-Valdes, J.R.Marino-Albernas, and V.Verez-Bencomo, J. Carbohydr. Chem., 1987, 5, 509. A.Gomez-Sanchez, M.Garcia-Martin, and C.Gasch, Carbohydr. Res., 1987, 164, 255. K.C.Nicolaou, R.A.Daines, T.K.Chakraborty, and Y.Oqawa, J. Am. Chem. SOC., 1987, 109, 2821. Y.Tamura, M.Kirihara, M.Sasho, S.Akai, J.Sekihachi, R.Okunaka, and Y.Kita, J. Chem. SOC., Chem. Commun., 1987, 1474. V.Nair and J.P.Joseph, Heterocycles, 1987, 25, 337. D.Loqanathan and G-Trivedi,Carbohydr. Res., 1987, 162, 117. H.Schildknecht and R.Milde, Carbohydr. Res., 1987, 164, 23. R.J.Outcalt, T.T.Wu, K.B.Cooke, and D.Larochelle, J. Agric. Food Chem., 1987, 35, 836 (Chem. Abstr. , 1987, 107,134 573) V.P.Khilya, V.G.Pivovarenko, and F.S.Babichev, Ukr. Khim. Zh. (Russ. Ed.) , 1986, 52, 187 (Chem. Abstr. , 1987, 106,67 584). S.G.Withers, I.P.Street, P.Bird, and D.H.Dolphin, J. Am. Chem. SOC., 1987, 109, 7531. Y.Saito, T.Watanabe, H.Hashimoto, and J.Yoshimura, Carbohydr. Res., 1987, 169, 171. Ya.V.Voznyi, I.S.Kalycheva, and A.A.Galdyan, Biorq. Khim., 1986, 2, 521 (Chem. Abstr., 1987, 106,67 585). S.M.Jain, K.K.Anand, B.K.Chandan, and C.K.Ata1, Indian J. Pharm. Sci., 1987, 49, 13 (Chem. Abstr., 1987, 107, 168 615). J.Singh and J.Singh, Indian J. Chem., Sect.B, 1986, 969 (Chem. Abstr., 1987, 107, 7451). I.Cerny, V.Pouzar, P.Drasar, and M.Have1, Collect. Czech. Chem. Commun., 1987, 52, 2521. P.N.Rao, A.M.Rodriquez, and D.W.Miller, J. Steroid Biochem., 1986, 25, 417 (Chem. Abstr. , 1987, 107, 198 782). L.N.Atopkina and N.I.Uvarova, Khim. Prir. Scedin.,1986, 451 (Chem. Abstr., 1987, 107,176 332). L.N.Atopkina, V.A.Denisenko, V.L.Novikov, and N.I.Uvarova, Khim. Prir. Soedin., 1986, 301 (Chem. Abstr., 1987, 107, 23596). E.S.H.El Ashry, Y.E1 Kilany, and A.Mousaad, J. Carbohydr. Chem., 1987, 6,

.

z,

609.

41 42 43 44 45 46

T.Wakamiya, K.Yamanoi, K.Kanou, and T.Shiba, Tetrahedron Lett., 1987, 28, 5887. L.F.Tietze, R..Fischer, and G.Remberq, Liebiqs Ann. Chem., 1987, 971. H.Saito, Y.Nishimura, S.Kondo, and H.Umezawa, Chem. Lett., 1987, 799. S.Esaki, S.Kamiya, and N-Shiba, AgriC. Biol. Chem., 1987, 51, 1459. H.Kessler, M-Kottenhahn, A.Klinq, and C.Kolar, Angew. Chem. Int. Ed. Enql., 1987, 26, 888. K.Kaike, M.Suqimoto, Y-Nakahara,and T.Oqawa, Carbohydr. Res., 1987, 162, 237.

Carbohydrate Chemistry

38 47 48 49 50 51 52 53 54

55 56 57 58 59 60 61

G.Shaw, M.C.Mok, and D.W.S.Mok, J.’Chem. Res., Synop., 1 9 8 7 , 1 1 0 (Chem. Abstr. , 1 9 8 7 , 107, 237 1 5 6 ) . A.A.Ansari, T.Frejd, and G.Magnusson, Carbohydr. Res., 1 9 8 7 , 161,2 2 5 . A.B.Barua and J.A.Olson, Biochem. J., 1 9 8 7 , 244, 2 3 1 (Chem. Abstr., 1 9 8 7 , 107, -

40 2 1 5 ) .

A.V.Nikolaev and N.K.Kochetkov, Izv. Akad. Nauk SSSR, Ser. Khim., 1 9 8 6 , 2556 (Chem. Abstr., 1 9 8 7 , 107, 217 9 5 7 ) . H.L&n, J. Carbohydr. Chem., 1 9 8 7 , 6, 301. B.Doboszewski and A.Zamojski, Carbohydr. Res., 1 9 8 7 , 164,470. N.K.Kochetkov, V.M.Zhulin, N.M.Malysheva, E.M.Klimov, and Z.G.Makarova, Carbohydr. Res., 1 9 8 7 , l-6.2, C8. N.K.Kochetkov, V.M.Zhulin, E.M.Klimov, N.M.Malysheva, Z.G.Makarova, and A.Y.Oh, Carbohydr. Res., 1 9 8 7 , I&, 241. B.Weqmann and R.R.Schmidt, J. Carbohydr. Chem., 1 9 8 7 , 6, 357. A.W.Mazur and G.D.Hiler, Jr., Carbohydr. Res., 1 9 8 7 , 168,1 4 6 . K.Bock and H.Pedersen, Acta Chem. Scand., Ser.B, 1 9 8 7 , 2, 6 1 7 . C.P.Fei and T.H.Chan, Tetrahedron Lett., 1 9 8 7 , 8, 849. K-Ajisaka, H.Nishida, and H.Fujimoto, Biotechnol. Lett., 1 9 8 7 , 2, 243 (Chem. Abstr., 1 9 8 7 , 107,20 3 0 8 ) . H-Paulsen, B.Helpap, and J.P.Lorentzen, Liebigs Ann. Chem., 1 9 8 7 , 431. J.Giqq, R-Giqq, S-Payne, and R-Conant, J. Chem. SOC., Perkin Trans.1, 1 9 8 7 , ~

1165. 62 63 64 65 66

J.R.Marino-Albernas, V.Verez-Bencomo, L.Gonzalez, and C.S.Perez, Carbohydr. Res., 1 9 8 7 , 165,1 9 7 . Z N a s h e d and C.P.J.Glaudemans, J. Org. Chem. , 1 9 8 7 , 52, 5 2 5 5 . V.Pozsqay and H.J.Jenninqs, J. Org. Chem., 1 9 8 7 , 52, 4635. K.G.I.Nilsson, Carbohydr. Res,, 1 9 8 7 , 167,9 5 . M.M.Palcic, O.P.Srivastava, and O.Hindsqau1, Carbohydr. Res., 1 9 8 7 , 159, 315.

67 68

S.A.Abbas, C.F.Piskorz, and K.L.Matta, Carbohydr. Res., 1 9 8 7 , 167,1 3 1 . R.R.Schmidt, T.Bar, and H.-J.Apel1, Angew. Chem. Int. Ed. Enql., 1 9 8 7 , 26,

69 70 71 72 73

K.Bock and S-Refn, Acta Chem. Scand., Ser.B, 1 9 8 7 , 41, 469. Y.Ito and T.Oqawa, Tetrahedron Lett., 1 9 8 7 , 8, 4701. O.P.Srivastava, O.Hindsgau1, Carbohydr. Res., 1 9 8 7 , 161,324. R.K.Jain, R.Dubey, S.A.Abbas, and K.L.Matta, Carbohydr. Res., 1 9 8 7 , R.Dubey, R.K.Jain, S.A.Abbas, and K.L.Matta, Carbohydr. Res., 1 9 8 7 ,

74 75

78 79 80 81 82 83 84

Y.Ito and T.Oqawa, Tetrahedron Lett., 1 9 8 7 , E,2723. V.M.Zhulin, E.M.Klimov, Z.G.Makarova, N.N.Malysheva, and N.K.Kochetkov, Dokl. m a d . Nauk SSSR, 1 9 8 6 , 289, 105 (Chem. Abstr. , 1 9 8 7 , 106,1 9 6 6 9 9 ) . A.B.Smith 111, and R.A.Rivero, J. Am. Chem. SOC., 1 9 8 7 , 109, 1 2 7 2 . A.B.Smith 111, K.J.Hale, and H.A.Vaccaro, J. Chem. SOC., Chem. Commun., 1 9 8 7 , 1026. A.B.Smith 111, K.J.Hale, and H.A.Vaccaro, Tetrahedron Lett., 1 9 8 7 , 28, 5591. P.FGqedi, J. Carbohydr. Chem., 1 9 8 7 , 6 , 377. S.Kamiya, S-Esaki, and N.Shiba, Agric. Biol. Chem., 1 9 8 7 , 2, 1 1 9 5 . S-Kamiya,S.Esaki, and N.Shiba, Agric. Biol. Chem., 1 9 8 7 , 51, 2 2 0 7 . J.F.W.Burger, E.V.Brandt, and D.Ferreira, Phytochemistry, 1 9 8 7 , 26, 1 4 5 3 . J.Thiem, V-Duckstein, A-Prahst, and M.Matzke, Liebigs Ann. Chem., 1 9 8 7 , 289. S J. Danishefsky, H G .Selnick, D .M Armistead , and F .E .Wincott, J . Am. Chem.

85 86

J. Jacquinet and P .Sinay, Carbohydr. Res ., 1 9 8 7 , 159, 229. P.Kosma, J.Gass, G.Schulz, R.Christian, and F.M.Unqer, Carbohydr. Res.,

793.

161,31. 165,

189.

76 77

.

1987, 87

I

SOC. , 1 9 8 7 , 109, 8119. -

.

167, 39.

88

T-Shimizu, S.Akiyama, T.Masuzawa, Y.Yanaqihara, S.Nakamoto, and K.Achiwa, Chem. Pharm. Bull. , 1 9 8 7 , 35, 8 7 3 . M.Kiso, M.Fujita, E.Hayashi, A.Hasegawa, and F.M.Unqer, J. Carbohydr. Chem.,

89 90

S.Nakamoto and K-Achiwa,Chem. Pharm. Bull., 1 9 8 7 , 35, 4537. M.Kiso, M.Tanahashi, A-Hasegawa, and F.M.Unqer, Carbohydr. Res., 1 9 8 7 ,

1987,

279.

5,

691.

163,

39

3: Glycosides and Disaccharides 91 92 93 94 95 96

97 98 9Y 100

101 102 103 104 105 106 107

108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132

C.Shimizu and K.Achiwa, Carbohydr. Res., 1987, 166,314. M.Numata, M.Sugimoto, K.Koike, and T.Ogawa, Carbohydr. Res., 1987, 163,209. D.Kantoci, D.Keglevic, and A.E.Derome, Carbohydr. Res., 1987, 162, 227. W.Kinzy and R.R.Schmidt, Liebigs Ann. Chem., 1987, 407. J.Farkas, M.Ledvina, J.Brokes, J.Jezek, J.Jajicek, and M.Zaora1, Carbohydr. Res., 1987, 163,63. K.Ikeda, T.Takahashi, H.Kondo, and K.Achiwa, Chem. Pharm. Bull., 1987, 35, 1311. M.Imoto, H.Yoshimura, M.Yamamoto, T.Shimamoto, S.Kusumoto, and T-Shiba, Bull. Chem. SOC. Jpn., 1987, 60, 2197. M.Imoto, H.Yoshimura, T.Shimamoto, N.Sakaguchi, S .Kusumoto, and T.Shiba, Bull. Chem. SOC. Jpn., 1987, 60, 2205. W.Kinzy and R.R.Schmidt, Tetrahedron Lett., 1987, 29, 1981. A.E.Zemlyakov, V.Ya.Chirva, and A.Ya.Khorlin, Bioorg. Khim. , 1986, 12, 1637 (Chem. Abstr. , 1987, 107, 176 446). M.Gerken and D.R.Bundle, Tetrahedron Lett., 1987, g,5067. T.Peters and D.R.Bundle, J. Chem. SOC., Chem. Commun., 1987, 1648. H.Yamada and M.Nishizawa, Tetrahedron Lett., 1987, 28, 4315. M.Ojika, K.Wakamatsu, H.Niwa, and K.Yamada, Tetrahedron, 1987, 43, 5275. S.A.Nepogodev, L.V.Bakinovskii, and N.K.Kochetkov, Bioorg. Khim., 1986, 12, 1139 (Chem. Abstr., 1987, 107,78 157). S.Luo and G.Ruecker, Planta Med., 1986, 412 (Chem. Abstr., 1987, 106, 99 352). D-Takaoka, Y.11, H.Nozaki, M.Nakayama, T.Tada, and S.Kooda, Tenneu Yuki Kagobutsu Toronkai Koen Yoshishu, 1986, E l 240 (Chem. Abstr., 1987, 107, 237 145). P.S.Steyn, F.R.Van Heerden, and R.Vleggaar, S. Afr. J. Chem., 1986, 2, 143 (Chem. Abstr. , 1987, 107,115 869) . N-Fusetani, K.Yasukawa, S .Matsunaga, and K.Hashimoto, Tetrahedron Lett., 1987, 28, 1187. E.R.Novik, V.M.Sokolov, V.I.Zakharov, and E.P.Studentsov, Zh. Obshch. Khim., 1986, 56, 2642 (Chem. Abstr., 1987, 107,217 950). H.S.Isbel1 and H.L.Frush, Carbohydr. Res. , 1987, 161,181. M.Cockman, D.G.Kubler, A.S.Oswald, and L.Wilson, J. Carbohydr. Chem., 1987, 6, 181. Y-Ichikawa, M.Isobe, D.-L.Bai, and T.Goto, Tetrahedron, 1987, 43, 4737. O.R.Martin, K.G.Kurz, and S.P.Rao, J. Org. Chem., 1987, 52, 2922. G.R.Perdomo and J.J.Krepinsky, Tetrahedron Lett., 1987, 28, 5595. Y.Guindon and P.C.Anderson, Tetrahedron Lett., 1987, 28, 2485. 1-Tvaroska and T.Kozar, Chem. Pap. (Chem. Zvesti), 1987, 41, 501. V.Pozsgay and H.J.Jennings, Tetrahedron Lett., 1987, 28, 1375. F.J.L.Aparici.0, F.Z.Benitez, F.S.Gonzalez, and J.L.A.Rose11, Carbohydr. Res. , 1987, 163,29. C.K.Zercher and L.R.Fedar, Carbohydr. Res., 1987, 165,299. H.B.Mereyala, Carbohydr. Res., 1987, 168,136. M.M.Ponpipom, R.L.Bugianesi, and T.J.Blake, J. Med. Chem., 1987, 30, 705. R.R.Schmidt, W.Frick, B.Haag-Zeino, and S.Apparao, Tetrahedron Lett., 1987, 28, 4045. N.Katagiri, H.Akatsuka, T.Haneda, and C.Kaneko, Chem. Lett., 1987, 2257. P-Lesimple, J.-M.Beau, and P.Sinay, Carbohydr. Res., 1987, 171,289. D.K.Hutchison and P.L.Fuchs, J. Am. Chem. SOC., 1987, 109, 4930. K.Luthman, M.Orbe, T.Waglund, and A.Claesson, J. Org. Chem., 1987, 3777. M.Cai, L.Dong, S.Wang, and T.Cheng, Gaodeng xuexiao Huaxue Xuebao, 1986, 1008 (Chem. Abstr. , 1987, 107, 198 787) . P.kllevi, M-Anastasia, P.Guffreda, A.Fiecchi, and A.Scala, J. Chem. SOC., Chem. Commun., 1987, 101. P.Allevi, M-Anastasia,P-Guffreda, A.Fiecchi, and A.Scala, J. Chem. SOC., Chem. Commun., 1987, 1245. G.D.Kini, C.R.Petrie, W.J.Hennen, N.K.Dalley, B.E.Wilson, and R.K.Robins, Carbohydr. Res., 1987, 159, 81. P.Kall and A.F&tsch, Czohydr. Res., 1987, 171, 301.

x,

z,

40 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149

150 151 152 15 3 154 155 156 157 158 159

160

161 162 163 164 165 166 167 168 169 170 171 172 1 73 174 175 176 177

Carbohydrate Chemistry R.R.Schmidt and G.Efenberqer, Liebigs Ann. Chem., 1987, 825. R.R.Schmidt and G.Efenberqer, Carboh dr. Res., 1987, 171, 59. J.A.Bennek and G.R.Gray, J. Org. Chei., 1987, 52,.298 A.Hosomi, Y.Sakata, and H.Sakurai, Carbohydr. Res., 1987, 171,223. A.P.Kozikowski, T.Konoike, and A.Ritter, Carbohydr. Res., 1987, 171,109. T-Kametani,K.Kawamura, and T.Honda, J. Am. Chem. SOC., 1987, 109, 3010. F.Nicotra, L.Panza, F.Rochetti, G.RUSSO, and L.Toma, Carbohydr. Res., 1987, 171, 49. D.Monti, P-Gramatica,G.Speranza, and P.Manitto, Tetrahedron Lett., 1987, 28, 5047. K.M.Sun, R.D.Dawe, and B-Fraser-Reid, Carbohydr. Res., 1987, 171,35. A.Giannis and K.Sandhoff, Carbohydr. Res., 1987, 171,201. P.S.Liu, J. Orq. Chem., 1987, 52, 4717. Y-Ichikawa,M.Isobe, M.Konobe, and T.Goto, Carbohydr. Res., 1987, 171,193. S.J.Danishefsky, S.DeNimo and P.Lartey, J. Am. Chem. Soc., 1987, 109, 2082. J.Herscovici, S-Delatre,and K-Antonakis,J. Orq. Chem., 1987, 52, 5691. K.Maruoka, K-Nonashita,T.Itoh, and H.Yamamoto, Chem. Lett., 1987, 2215. D.P.Curran and Y.-G.Suh, Carbohydr. Res. , 1987, 171,161. M-Brakta, F.Le Borqne, and D.Sinou, J . Carbohydr. Chem., 1987, 6, 307. L.V.Dunkerton, J.M.Euske, and A.J.Serino, Carbohydr. Res. , 1987, 171,89. V.Bellosta and S.Czernecki, Carbohydr. Res., 1987, 171,279. H.Kunz, B.Miiller, and J.Weissmiiller, Carbohydr. Res., 1987, 171,25. R.R.Schmidt, R.Preuss, and R.Betz, Tetrahedron Lett., 1987, 28, 6591. M.Ramaiah, Tetrahedron, 1987, 43, 3541. Y-Araki, T.Endo, M.Tanji, T.Naqasawa, and Y.Ishido, Tetrahedron Lett., 1987, 28, 5853. B-Giese, J-Dupuis, M.Leisinq, M.Nix, and H.J.Lindner, Carbohydr. Res. , 1987, 171,329. R.Blattner, R.J.Ferrier, and R.Renner, J . Chem. SOC., Chem. Commun., 1987, 1007. T.-C.Wu, P.G.Goekjian, and Y.Kishi, J. Orq. Chem., 1987, 52, 4819. S.A.Babirad, Y.Wanq, and Y.Kishi, J. Orq. Chem., 1987, 52, 1370. P.Allevi, M.Anastasia, P.Ciu€€reda, A.Fiecchi, and A.Scala, J. Orq. Chem., 1987, 52, 5469. Y.Araki, N.Kobayashi, Y.Ishido, and J.Naqasawa, Carbohydr. Res., 1987, 171, 125. T-Mukaiyama and S.Kobayashi, Carbohydr. Res., 1987, 171,81. K.Narasaka, Y.Ichikawa, and H.Kubota, Chem. Lett., 1987, 2139. O.R.Martin, Carbohydr. R e s . , 1987, 171,211. F.Nicotra, L.Panza, and G.RUSSO, J. Org. Chem., 1987, 52, 5627. D.R.Mootoo, V.Date, and B.Fraser-Reid, J. Chem. Soc., Chem. Commun., 1987, 1462. G.W.J.Fleet and L.C.Seymour, Tetrahedron Lett., 1987, 28, 3015. F. Freeman and K. D.Robarqe , Carbohydr Res. , 1987, 171,1. B.E.Marganoff, S.O.Nortey, R.R.Inners, S.A.Campbel1, A.B.Reitz, and D-Liotta, Carbohydr. Res., 1987, 171,259. A.Bandzouzi and Y.Chapleur, Carbohydr. Res., 1987, 171,13. C.S.Wilcox and M.D.Cowart, Carbohydr. Res., 1987, 171,141. R.A.Outten and G.D.Daves, J. Orq. Chem., 1987, 52, 5064. I.Maeba, O.Hara, M.Sukuki, and H.Furukawa, J. Orq. Chem., 1987, 52, 2368. I.Maeba, M.Suzuki, O.Hara, T-Takeuchi,T.Iijima, and H.Furukawa, J. Org. Chem., 1987, 52, 4521. A.P.Kozikowski, G.Q.Lin, and J.P.Sprinqer, Tetrahedron Lett., 1987, 28, 2211. F.J.Lopez-Aparicio, R.Robles Diaz, M.T.Plaza Lopez-Espinosa, and A.M.Perez Rojas, An. Quim., Ser.C, 1986, 82, 179 (Chem. Abstr., 1987, 107,154 611). A.P.Kozikowski and X.-M.Cheng, J. Chem. Soc., Chem. Commun., 1987, 680. ~

.

4 Oligosaccharides 1

General

As before, this Chapter deals with specific tri- and higher oligosaccharides; most references relate to their syntheses by specific chemical methods. It does not deal with compounds made by the oligomerization of monosaccharide derivatives, nor does it deal with the cyclodextrins (although this year, for the first time, mention is made of the chemical synthesis of such compounds). The synthesis of, e.g., pentasaccharides is dealt with under that heading, and the required preparations of constituent parts are assumed and are not covered in their respective sections. Frequently, specific derivatives of the basic conpounds are involved and this fact is often not recorded in the structural formul-aeused. A review has appeared on the synthesis of oligosaccharides, glycopeptides and complex oligosaccharides of glycoproteins and on 1 the conformational analysis of the oligosaccharide sequences. Another has been published on chiral selection and chiral induction 2 using regiospecifically di- and poly-substituted 5-cyclodextrins. 2,3,~-Tri-~-acetyl-6-~-tert-butyldiphenylsilyl-a-D-galactopyranosyl chloride has been applied in the synthesis of B-1+6 linked D-galactose oligosaccharides, and various substituted derivatives of the dimer and trimer were made. 3 2

Trisaccharides

2.1 Linear Homotrisaccharides.- The a-(1-+2)-linked trimer of Dglucopyranose (kojitriose) and the tetramer and pentamer have been ~ y n t h e s i z e d ,as ~ have the a - - ( l + u - a - ( 1+3) and a-(1+3)-a-(1+4) isomers, in connection with studies of n i g e r ~ i n . ~In the D-mannopyranose set of compounds the a-(1+2)-a-(1+2), a-(l+2)-a-(l+3) and the a-(1+2)-a-(1+6) trimers were made as their 6"-phosphates which 6 are the end groups of oligosaccharide chains of lysosomal enzymes. In the course of the same work the a-(1+2)-a-(1+3) and the a-(l+2)a-(1+6) compounds were made with "spacer groups" attached at the

Carbohydrate Chemistry

42

anomeric centres and phosphate groups at the non-reducing end group primary positions. 7 The a-(l-+4)-a-(l+4) linked D-galactose trimer has been made and has phytoalexin eliciting activity,' and the heptose trimer (1) of the core region of the Gram-negative bacterial polysaccharides has also been prepared. The P - ( 1+4) linked-D-galactose trimer has been reported as one of a sequence of oligomers which can be made by a 10 systematic approach,

2.2 Linear Heter0trisaccharides.- The following trisaccharides having D-glucose at the reducing termini have been synthesized (the first twc B-linked to ceramide) : g-a-C-Galp-( 1+4)-g-B-D-Galp-B-D0-a-0-Galp-( 1+3)-g-B-D-Galp-B-D-Glc," O-@-D-GlcpUA-(l+Q)Glc ,I1 B-D-Galg-D-Glc, (a Klebsiella po1;ysaccharide constituent) ,I2 O-a-DNeug5Ac-(2+6)-g-B-D-Galp-(1+4)-D-Glc (present in human milk), 15 O - ~ - D - N ~ L I ~ ~ A C - (-~ + ~ ) - O - B - D - G ~ ~ ~ - ( ~(part + ~ ) -of D - aG ~ganglioside C

14chain). The following o t h e r hexose-terminating trimers have also been reported: O-B-D-GaipNAc-(1+4)-g-~-D-GlcpNAc-(l-+2)-D-Man (and the 4"-sulphate) ,I5 g-a-D-Manp-( 1+2)-g-a-D-Manp-( 1 q )-D-Gal and O-a-D-Manp-(1-+2)-g-B-D-Manp-(l+3)-D-Gal. 16 ,i7 -

Compounds terminating in 2-aminohexose units to have been synthesized are: g-a-D-KDOp-(2+6)-~-B-D-GlcNH2p-(1+6)-D-GlcNH2 (a lipid A analogue having both amino groups acylated with a long chain fatty acid) ,I8 0-a-D-KDOp-( 2+4)-g-a-D-KDOp-(2-+6)-D-GlcNH2 (the repeating unit of the inner core of a lipopolysaccharide),19 O-B-DGlcpNAc-( 1+3)-g-B-D-Galp-( 1+4)-D-GlcNAc, 2 o 0-8-D-GlcpNAc-( 1+3)-g-BD-Galp-( 1-+3)-g-B-D-GlcpNAc-Ph-pNO2 ,23 g-B-D-GlcpNAc-( 1+3)-g-B-DGalp- ( 1+3) -g-a-D-GalpNAc-Ph-pN02 , 0-a-D-Glcp ( 1+3) -g-a-L-Rhap(1+3)-ManpNAc. 21 The KDO-terminating trimer g-a-L-Rhap-( 1+3) -0-a-LRhap-( 1+8)-D-KDO has been isolated from an AcinetobacterY2* and the following L-rhamnose-terminating compounds have been synthesized: 0-6-D-ManpNAc-( 1+4)-g-a-D-Glcp-( 1+2)-L-Rha,23 and g-B-D-Glcp-( 1+4)0-a-and B-L-Rhap-(1+2)-L-Rha (with 2-methyl groups at 0-3,-2',-3', 24725 - 3" and -6" ) More unusual compounds to have been prepared are the deoxysugar

*'

.

43

4: Oligosaccharides

OH

(4)

26 compounds (2), (3) and (4) which are components of auretoic acid, 26 a derivative of an isomer of the trisaccharide of mithramycin and the E, D, C trisaccharide of the antibiotic respectively.27 2.3 Branched Heterotrisaccharides.- Compounds of this category to have been reported are: ~-B-D-GlcpNAc-(1+4)-~-~B-D-GlcpNAc-(1+3)10-a-D0-a-D-Manp-( 1.+3)-Q-Ca-U-Glcp-( 1 4 )I-D-Gal,16929 Manp--( 1+3)-o-[B-D-Glc~-(l'4) l-D-Ga129 and g-B-D-GlcpNAc-( 1+6)-0C B-D-GlcpNAc- ( 1+3) I-D-Gal . j0

3 Tetrasaccharides As with the trisaccharides, the following tetrasaccharides are classified according to whether they have linear or branched chains, and then by the nature of the sugars at the reducing ends. 3.1 Linear Tetrasaccharides.- Compounds of this group to have been isolated. from natural products or synthesized are: g-B-D-Galp-(1+4) ( 1 4 )-g-B-D-Galp- ( 1 4 )-D-Glc ,31 2-B-D-Galp-( 1 4 )-2-0-B-D-GlcpNAcB-D-GlcpNAc-( 1+ 3)-eg-~Gale-(l~)-l)-~lc,~~ (the repeating unit of the capsular polysaccharide of Streptococcus pneumoniae which has been made synthetically by way of a tetramer 1,2-Q-cyanoethylidene derivative) ,j2 0-B-D-GlcpNAc-(1+3)-g-B-D-Galp-( 1+3)-O-B-D-GlcpNAc( 1+3)-D-Ga1,28 i-B-D-Galf-( l-+)-g-B-D-Galf-< 1+5)-O-B-D-Galf-( 1+5)D-Galf (a unit of the cell wall polysaccharide of Aspergillus )niger) 33 and c-a-D-Manp-( 1+6)-g-B-D-Manp-( 1+4)-~-B-D-Glc~NAc-(l+4 D-GlcpNAc (isolated from urine of calves with a-mannosidosis). 3Q

D-Quinovosyl-L-rhamnosyl-D-glucosyl-D-fucose tetramers which have been isolated from a plant root as cyclic esters are referred to in Chapter 7.

44 3.2

Carbohydrate Chemistry

Branched Tetrasaccharides.- Compounds synthesized:

g-a-D-Manp-

(1+2)-g-a-D-Manp-( 1+3)-g-Ca-D-Glcp-( 1 4 )I-D-Gal , I 6'29 0-a-D-Manp( 1+2)-g-a-D-Manp- ( 1+3) -0-C 0-D-Glcp- ( 1+4 ) I-D-Clal, l6 '29 0-B-D-Galp( 1+4)-g-B-D-Galp-NH2-g-[ 0-D-Galp- (1+3)I-D-GalNH 35 and 2-a-D-Manp-

*

(1+6)-~-~a-D-Manp-(1+3)l-~-~-D-Talp-(l+~~-D-GlcNAc. 36

4 Pentasaccharides The a-(1+4) linked D-glucose pentasaccharide having a 2-pyridylamino group at C-6 of tne non-reducing terminus and as an a-linked p-nitrophenyl glycoside has been prepared from amylose as a s u b s trate for a-amylase 37 0-a-L-Rhap- ( 1+2) -2-a-L-Rhap- ( 1+3)-2-a-LRhap-(l+3)-~-B-D-GlcpNAc-(l+2)-g-a-L-Rhap-OMe has been synthesized,38 as has the methyl glycoside (5) which represents the sequence in

.

heparin responsible f o r binding and activation of the anticoagulant protein. 39 The synthesis o f the ceramide pentasaccharide(6, X hapten)

h a s been reported4'

as has that of the non-reducing pentasaccharide ( 7 ) which is a component of the glycolipid antigen of E. Smegmatis.41

45

4 : Oligosaccharides

5 Hexasaccharides Cyclomaltohexaose has been synthesized formally from maltose in a multistep process.42,43 The major constituent of a coaggregation polysaccharide of Streptococcus sangius has been characterized as: 0-a-D-GalpNAc-

(1+3)-~-B-L-Rha~-(1~4)-O-~-D-Glc~-(l+6)-~-~-D-Galf-(l~6)-~-B-DGalpNAc-( 1+3)-D-.Gal01~~- and the unusual hexasaccharide ( 8) has been identified as the carbohydrate portion of steroidal glycosides of toxic oriental medicines.45

6 Higher Saccharides The B-(1+5) linked D-galactofuranose heptasaccharide linked to L-homoserine, which is similar t d the extra-cellular galactomannan of As er illus species, has been synthesized by a solid-phase pro=nd the phytoalexin elicitor of soyabean ( 9 ) has also II 7 been synthesized.

The B - ( 1 - + 3 ) linked tetrarner of ;-acetyllactosamine has been prepared by a block approach,48 and the first total synthesis of cyclomalto-octaose (6-cyclodextrin) has been developed from Incubation of a-maltosyl fluoride with pullulanose gave maltose.49 6 - ~ - a - r n a l t o s y l c y c l o m a l t o h e x a o s e as well as other branched c y c lomalt0-o ligosac charides 50 The stereocontrolled synthesis of compound (lo), which has phytoalexin elicitor activity, has been reported.5 1

.

References 1 2 3 4

H.Paulsen, Stud. Org. Chem. (Amsterdam), 1986, 25 (New Synth. Method of Funct. Interesting Compd.) 243 (Chem. Abstr. , 1987, 107, 23 583) 1-Tabushi, Pure Appl. Chem., 1986, 58, 1529. E.M.Nashed and C.P.J.Glaudemans, J. Org. Chem., 1987, 52, 5255. K.Takeo and Y .Suzuki, Carbohydr. Res. , 1987, 162,95.

.

46 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33

34 35 36 37 38 39 40 41 42 43 44 45 46 47

Carbohydrate Chemistry K.Takeo and T.Imai, Carbohydr. Res., 1987, 165, 123. 0.P.Srivastava and O.Hindsgau1, Carbohydr. Res., 1987, I&, 195. 0.P.Srivastava and O.Hindsgau1, J. Org. Chem., 1987, 52, 2869. Y.Nakahara and T.Ogawa, Tetrahedron Lett., 1987, 28, 2731. ____ K-Dziewiszek,A.Banaszek, and A.Zamojski, Tetrahedron Lett., 1987, 28, 1569. P.Kov& and R.B.Taylor, Carbohydr. Res., 1987, 167,153. K.Koike, M.Sugimoto, S.Sato, Y.Ito, Y.Nakahara, and T.Ogawa, Carbohydr. Res., 1987, 163,189. A.K.Sarkar and N.Roy, Carbohydr. Res., 1987, 163,285. V-Pozsgay, H.J.Jenninqs, and D.L.Kasper, J. Carbohydr. Chem. , 1987, 6, 41. K.Okamoto, T-Kondo, and T.Goto, Tetrahedron, 1987, 43, 5919. V.Hindsgau1, 0-Hindsgaul, and J.U.Baenziger, Can. J. Chem., 1987, 65, 1645. V.I.Torgov, C.A.Panossian, and V.N.Shibaev, Carbohydr. Res., 1987, 97. V.I.Torgov, C.A.Panossian, and V.N.Shibaev, Bioorg. Khim., 1986, 12, 559 (Chem. Abstr., 1987, 106,33 399). H.Paulsen and M.Schuller, Liebigs Ann. Chem. , 1987, 249. H-Paulsen, M.Stiem, and F.M.Unger, Liebigs Ann. Chem., 1987, 273. R.L.Thomas, R.Dubey, S.A.Abbas, and K.L.Matta, Carbohydr. Res., 1987, 169, 201. H.Paulsen and J.P.Lorentzen, Carbohydr. Res., 1987, 165,207. H.Brade, A.Tacken, and R-Christian, Carbohydr. Res., 1987, 167,295. L.Panza, F.Ronchetti, G.RUSSO, and L.Toma, J. Chem. SOC., Perkin Trans. I, 1987, 2745. T.Fujiwara, G.O.Aspinal1, S.W.Hunter, and P.J.Brennan, Carbohydr. Res., 1987, 163,41. T.Fujiwara and S.Izumi, Agric. Biol. Chem., 1987, 51, 2539. J.Thiem, M-Gerken, B.Schottmer, and J.Weiqand, Carbohydr. Res. , 1987, 164, 327. J.Thiem and B-Schottmer, Angew. Chem. Int. Ed. Engl., 1987, 26, 555. S.A.Abbas, K.Kohata, and K.L.Matta, Carbohydr. Res., 1987, 161,39. V.I.Torgov, C.A.Panossian, and V.N.Shibaev, Bioorg. Khim., 1986, 2, 562 (Chem. Abstr. , 1987, 106,33 400) . D.M.Whitfield, C.J.Ruzicka, J.P.Carver, and J.J.Krepinsky, Can. J. Chem., 1987, 65, 693. H.Paulsen and K.-M-Steiger, Carbohydr. Res., 1987, 169, 105. N.K.Kochetkov, N.E.Nifant'ev, and L.V.Backinowsky, Tetrahedron, 1987, 43, 3109. G.H.Veetneman, P.Hoogerhout, P.Westerduin, S.Notermans, and J.H.Van Boom, Recl. Trav. Chim. Pays-Bas, 1987, 106,129 (Chem. Abstr. , 1987, 107,217 959). C.D.Warren, S.Nakabayashi, and R.W.Jeanloz, Carbohydr. Res., 1987, 169, 221. W.Kinzy and R.R.Schmidt, Carbohydr. Res., 1987, 164, 265. H.Paulsen and T.Peters, Carbohydr. Res., 1987, 165,229. K.Omichi and T-Ikenaka, J. Chromatogr., 1987, 420, 158. B.M.Pinto, D.G.Morissette, and D.R.Bundle, J. Chem. SOC., Perkin Trans. I, 1987, 9. M.Petitou, P.Duchaussoy, I.Lederman, J.Choay, J.-C.Jacquinet, P.Sinay, and G.Torri, Carbohydr. Res., 1987, 167, 67. S.Sato, Y.Ito, T.Nukada, Y.Nakahara, and T.Ogawa, Carbohydr. Res., 1987, 167, 197. Z.Szurmai, J.Kerekgyarto, J.Harangi, and A.Liptak, Carbohydr. Res., 1987, 164, 313. Y.Takahashi and T.Ogawa, Carbohydr. Res., 1987, 164,277. Y.Takahashi and T.Ogawa, Denpun Kagaku, 1986, 33, 133 (Chem. Abstr., 1987, 107, 154 622). F .C.McIntire , C.A. Bush, S S .Wu, S .C.Li , Y .T.Li , M. McNeil , S S Tjoa , and P.V.Fennessey, Carbohydr. Res. ,. 1987, 166,133. Y.Oshima, T.Hirota, and H.Hikino, Heterocycles, 1987, 26, 2093. G.H.Veeneman, S.Notermans, R.M.J.Liskamp, G.A.van der Marel, and J.H.van Boom, Tetrahedron Lett., 1987, 2, 6695. P.Fugedi, W-Birberg, P.J.Garegq, and A.Pilotti, Carbohydr. Res., 1987, 164, 297.

.

..

47

4: Oligosucchurides 48 49 50 51

J.Alais and A-Veyrieres, Tetrahedron Lett., 1987, 28, 3345. Y.Takahashi and T.Ogawa, Carbohydr. Res., 1987, 169, 127. S.Kitahata, Y.Yoshimura, and S.Okada, Carbohydr. Res., 1987, Y.Nakahara and T.Ogawa, Carbohydr. Res., 1987, 167, C1.

159, 303.

Ethers and Anhydro-sugars 1

Ethers

Methyl Ethers.- 4-2-Methyl-B-D-xylopyranoside has been identified as the sugar moiety in the new 1ip;nan slycoside cleistanthoside I3 from the heartwood of Cleistanthus collinus. 1

A number of methyl ethers of methyl a-n-~alactopyranoside have been prepared by standard partial methylation and chromatographic

*

separation procedures. The methylation of methyl a-D-hexopyranosides with diazomethane in the presence of small amounts of water has been described. Long reaction times with diazomethane in wet ether gave all the partially methylated derivatives. T h e presence of electrolytes such as sodium or potassium phosphates enhanced the degree of methylation resulting in the preferential formation of mixtures of the tri-g-methyl derivatives. The synthesis of 13Cl-enriched 5-2-methyl pentoses has been achieved via [13C7] C1cyanide addition to the appropriate 4-g-methyl tetrose and separation of the C-2 epimers by ~ h r o m a t o g r a p h y . ~Some phosphates of K30, 3-deoxy-D-arabino-heptulosonic acid, and 3-deoxy-D-gluco-octulosonic acid have been converted into methylated derivatives to help the detection of such phosphates in lipopolysaccharides.5 Other Alkyl and A r y l Ethers.- The regioselective alkylation at 0-3 of methyl 2,6-dideoxy-a- and B-L-lyxo- and a-L-arabino-hexopyranosides through activation as the dibutylstannylidene acetals has been described, whereas phase transfer catalysed benzylat ion (Bu4NBr, BnBr, NaOH) of benzyl 2,6-dideoxy-a-L-lyxo-hexopyranoside The adduct afforded a 3 : l mixture of' the 4- and 3-g-benzyl

ether^.^

(1) obtained on treating penta-0-acetyl-6-D-glucopyranose with piperidine was used to synthesize some 2-Q-alkyl-D-glucose A new approach to B-D-mannopyranoside derivatives derivatives (2). selectively alkylated at 0-3 and 0-6 has been exemplified by the preparation of' methyl 3,6-di-0-allyl-2,4-di-2-benzoyl-B-D-mannopyranoside f r o m methyl f3-D-galactopyranoside. The galactoside was selectively allylated at 0-3 and 0-6 via activation as a

49

5: Ethers and Anhydro-sugars

or””

CH,OR*

OH

AcO

OAll

(1)

dibutylstannylidene acetal. Inversion of configuration at C-2 and C-4 was effected by tetrabutylammonium benzoate mediated displacement of the g-2 and 0-4 trifluoromethanesulphonyl esters.9 A variety o f 3-g-alkyl-, alkenyl-, w-hydroxyalkyl- and w-methoxyalkylD-glucoses and 3-2-alkyl-D-alloses have been synthesized conventionally by alkylation of the corresponding 1,2:5,6-di-gisopropylidene-D-hexofuranoses, and their cytotoxicity against leukemia cells, antimicrobial activity, and plant growth inhibitory A number of partially benzylated derivatives effects determined.” of 6-deoxy-D-glucose have been prepared from the corresponding 11 D-glucose ethers by a conventional 6-deoxygenation procedure. Per-g-butylated methyl glycosides have been synthesized under phase 12 transfer conditions. The cleavage of 4,6-2-benzylidene and ‘4,6-g-(p-methoxybenzylidene) acetals of hexopyranosides by diisobutylaluminium hydride has been reported .I3 D-Glucose derivatives gave predominantly the 4-g-benzyl or 4-2-p-methoxybenzyl ether, e.g., ( 3 ) , as with LAH/ A1C13. In the D-altro series the 6-2-benzyl ether, e.g., (4),

OBn

(3)

OBn

(4)

predominated, although the ratio of 6- to 4-ether was somewhat variable depending on the starting material. Using LiEt BH/TiCIQ, 3 one altro derivative gave predominantly a 4-g-p-methoxybenzyl ether. A novel selective debenzylation of 6-D-ribofuranoside derivatives offers a route to partially protected ribofuranose compounds potentially useful f o r nucleoside synthesis. Thus treatment o f the 4-chlorobenzyl ether (5) with stannic chloride and subsequent hydrolysis afforded (6).I4 It was proposed that tincatalysed anomerization is followed by chelation of the tin species between 0-1 and 0-2 activating the 2-benzyl ether to give a

Curbohydrate Chemistry

50 CHzOR

CH20R

OR

OR

CH20Bn

OMe

OR

OH

OBn 0

(8)

R = CH2C6H4CL(p)

2-g-trichlorostannyl intermediate which is hydrolysed on work-up. The unsubstituted benzyl ether gave much more of the product of internal C-glycosidation (7). The reaction is not general though, since the arabiEoside (8) under the same conditions rescted very s l o w l y to give mainly the produe’, of glycoside hydrolysis as well as some internal C-glycosidation. A chemoselective qlycosidic debenzylation in the presence of another benzyl ether has been effected by hydrogenolysis ( D d / C , H2, THF/EtOH 1:l) .I5 In the selectlve acetolysis of methyl 2 , 3 , 4 , 6 - t e t r a - O - b-e n z y l - a - D - m a n n C pyranoside, the relative reactivity of groups was l-OKe>6-PRn~4-OEn> 3-OBn-2-OEny and this permitted the synthesis of a range of

partially benzylated acetylated mannopyranose derivatives required as manncpyranosylating synthons. The rate of acetolysis of various benzylated and acetalate3 methyl 6-D-mannopyranosides was a l s o studied .I6 Anhydrous ferric chloride in dichloromethane has been used to cleave benzyl and p-phenylbenzyl ethers. Methyl ethers and acyl groups were not affected. Thus the mannopyranoside derivative (9) afforded 52% of diol (10) after brief treatment with the reagent .I7 A full paper on the catalytic transfer hydrogenolysis of benzylated 1,6-anhydro-@-D-hexopyranoses to give partially 0-benzoylated derivatives has been published. l8 (see Vol .20 p . 5 5 )

Acetonation of lactose with 2-rnethoxypropene/TsOH/DMF

gave the

and the 3,2’:4’,6’-di-acetal (54 and 21% isolated vields respectively, the latter after acetylation), and not t h e 6 , 2 ’ : b ’ , 6 ’ diacetal reported previously (SPR Vol.14, p . 4 5 ) . Studies with benzyl B-lactoside revealed initial formation of the 6,6’-bis-g-

4’,6’-mono-

(1-methoxy-1-methylethyl) derivative, (45% yield using Py.TsOH as

51

5: Ethers and Anhydro-sugars catalyst), and this observation led to the conversion of benzyl 3’,4’-~-isopropylidene-lactoside into the macrocyclic ether (11) through 6,6’ protection.19

Silyl Ethers.- Use of the diphenylmethylsilyl ether protecting group has been reported.2o This group generally has intermediate stability between the trimethylsilyl and the tert - butyldimethylsilyl ether groups. Studies on the selective silylation of methyl a - and 6-D-aldohexopyranosides with tert -butyldimethylsilyl chloride have revealed some preparatively useful reactions.21 Thus methyl 2,6-di-O-tert - butyldimethylsilyl-a-D-glucopyranoside is available in 7 0 % yield from methyl glucoside. Similarly, the 2,6-disubstituted a-galactoside (84%), the 2,3,6-trisubstituted a-galactoside ( 5 7 % ) , the 2,6-disubstituted a-mannoside (50%) and the 3,6-disubstituted a-mannoside (80%) were prepared from the parent methyl a-D-aldohexopyranosides. B-Glycosides did not give preparatively useful yields.

2

Intramolecular Ethers

(Anhydro-sugars)

0xirans.- Treatment of the cis-alkene ( 1 2 ) with MCPBA gave epoxide (13) and its isomer in a 1.8:1 ratio whereas Sharpless epoxidation (1 month,-lO°C) gave exclusively isomer using diethyl (=)-tartrate CHZOH

CHZOH

R o b o

& : B

- OEt

- OEt ( 14)

(12)

(’3)

f?

= 6 n or

R

O

)

(15) OAc CH2C6H4Br(p)

(13) which was required for the synthesis of antileukemia olguine analogues.22 The crystalline 1,2-anhydro-a-D-galactopyranose derivatives (14) were prepared from the corresponding €3-glycosyl fluorides (15) in good yield by treatment with potassium tert-butoxide in refluxing tetrahydrofuran .23 An improved procedure has been described for the synthesis of epoxide (16) in 33% yield in five steps from levoglucosan. Nucleophilic opening of this epoxide occurred as expected with standard nucleophiles, although treatment with Me,Mg in refluxing dioxan gave only 32% of the desired product,

52

Carbohydrate Chemistry

presumably due to steric effects with the bulky n ~ c l e o p h i l e . ~The ~ sucrose epoxide derivatives (17) and (18) have been synthesized and their reactions with nucleophiles studied. Both epoxides incorporated the nucleophile (e.g., N 3 - , C1-, Br-) at C-4' on ring opening.25 The reaction of 6-2-acetylsucrose with sulphuryl chloride in chloroform/pyridine gave, after dechlorosulphation and acetylation, a mixture of (19) and (20). The chlorine atoms at C - 4 ' in these compounds were postulated to be derived from the chloride ion opening of the isomeric C-3',4' epoxides. Compound (20), after deacetylation, was reported to be 2,200 times sweeter than sucrose.26 A 1,6;2,3-dianhydrideY proposed as a useful intermediate for the chiral synthesis of polypropionate derived natural products, is mentioned in Chapter 14. A comprehensive analysis of the H ' and 13C-n.m.r. data for the anomeric pairs of allo, manno- and talo-isomers of methyl 2,3anhydro-4,6-~-benzylidene-D-aldohexopyranosides has been reported using 2-D homo- and hetero-correlation techniques ,27 and an analysis of the conformation in solution of benzyl 2,3-anhydro-4azido-4-deoxy-pentopyranosides has been made using H' n .m.r. 28 spectra.

Other Anhydrides.- The synthesis of polysaccharides with a regular structure has been reviewed covering mostly the polymerization of anhydro-sugars. 29 1,5-Anhydro-D-fructose has been discovered to be the precursor of microthecin in the fungus Morchella vulgaris. It exists as the 2,6-hemiketal in solution and its structure was confirmed by X-ray analysis of its derived oxime. 30 An improved procedure for the preparation of 1,6-anhydro-B-Dglucopyranose has been described. Treatment of 1,2,3,4-tetra-gacetyl-6-g-trityl-B-D-glucopyranose with Lewis acids (SnC14 or TiC14) afforded tri-Q-acetyl-1,6-anhydro-B-D-glucopyranose in 78%

5: Ethers and Anhydro-sugars

53 The synthesis of some 1,6-anhydro-

yield on a 0.1 mole scale.”

disaccharides by base treatment of the respective arylglycosyl sulphones has been reported.” The synthesis of 1,3-anhydro-B-Drhamnopyranose ethers (21) from D-mannose hz>s also been reported. The intermediate methyl glycoside (22) was transformed directly to a glycosyl chloride followed by 1,3-anhydride formation (Scheme 1) .33 The same group has also described34 the preparation of the enantiomers of (21) from L-rhamnose by similar procedures.

L

o

Reaction of 2,3,4-trii-0-benzyl-D-g1ucose with DAST gave mostly 3,6-anhydro-2,4-di-~-benzyl-6-D-glucopyranosyl fluoride, due to 3-0-benzyl participation, rather than the desired 1,6-difluoride. 35 Similarly treatment of (23) with cesium fluoride gave the corresponding 3,6-anhydride instead of the desired 6-fluoride. 36 1,4:3,6-Dianhydro-a-D-mannopyranose (24), isolated as a stable crystalline solid, is formed in 75-80% yield along with 5-10% of 1,4:3,6-dianhydro-D-fructose (25) on flash vacuum thermolysis of isomannide dinitrate (26) (Scheme 2). Isosorbide dinitrate (the C-2 epimer of (26)) gives a 6:3:1 mixture of (25), (24) and the C-2 epimer of (24) in 80% yield.37 A chiral product (27), derived from an asymmetric Diels-Alder reaction of furan, has been converted into 2,5-anhydro-3,4-g-isopropylidene-D-allose (28) by

standard methods. 38 The 2,6-anhydroheptose (29) has been obtained by reduction of the correponding glucosyl cyanide. 39 Depending upon the reaction solvent, 1,2-di-O-acety1-3,5,6-tri-g-benzyl-Dallofuranose can be converted by reaction with SnC14 either to 2-~-acetyl-1,6-anhydro-3,5-di-~-benzyl-~-D-allofuranose(50%)

54

Carbohyd-ate Chemistry

(in dichloromethane) as reported in the patent literature, or to (30) (57%) (in toluene) .40 Sugar lactones the lY6';1',6-dianhydride (31) and (32) in the presence of benzyl-amine both gave rise to the

OBn

OAc

chiral oxetan (33). 41 When the benzyl-amine is replaced by K CO / 2 3 MeOH a mixture of methyl esters analop,ous to (33) and its C - 5 epimer is formed from both (31) and (32). The anhydrosucrose derivative (34) was obtained when, on deacetylation, the C-2

alkoxide added in Michael fashion to an a,B-unsaturated ester ~)-2,6-Dioxabicyclo[3.3.0]octan-3-one function at C-6'. 42 has been synthesized from D-glucose by way of the 3,6-anhydro-5deoxy-D-glucose derivative ( 3 5 ) . 43 During a study of the behaviour of 3-deoxy-D-manno-oct-2-ulosonic acid (KDO) in dilute acid, the 2,7-anhydro-sugar ( 3 6 ) was isolated from the equilibrium mixture 44 formed. 1 2 Further studies on the relative rates of H/ H exchange using Raney nickel in 2H20 have allowed the selective labelling of 1,6anhydro-galactopyranose at C-3 and 1,6-anhydro-galactofuranose at

(z,

55

5: Ethers and Anhydro-sugars

C-2. 45 The photobromination of 1,5-anhydropentofuranose derivatives and subsequent metal deuteride reduction of the resulting 5-exo-brcmides gave C-5 chirally deuterated

1,5-anhydropentofuranoses. The stereochemistry of the reduction was discussed in terms of effects of C-2 arld C - 3 substituents. 46 Products were mainly or exclusively the 5-S-*H derivative. Anodic oxidation of levoglucosan in MeOH/Ru4NC104 gave methyl B-D-arabinopyranoside in 47% yield. At controlled p H ( - 7 ) , D-arabinose was obtained. Levoglucosenone under the same conditions gave a mixture of polymers. 47

References 1

K.V.Sastry, E.V.Rao, J.G.Buchanan, and R.J.Sturgeon, Phytochemistry, 1987,

26, 1153.

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

17 18 19 20 21

E.V.Evtushenko, E.Yu.Plisova, and Yu.S.Ovodov, Bioorg. Khim., 1986, 2, 1366. Y.Inaue and K.Nagasawa, Carbohydr. Res., 1987, 168,181. J.R.Snyder and A.S.Serianni, Carbohydr. Res., 1987, 163,169. H.Brade, H.Mol1, S.R.Sarfati, and D.Charon, Carbohydr. Res., 1987, 167,291. C.Monneret, R.Gagnet, and J.-C.Florent, J. Carbohydr. Chem., 1987, 5, 221. S.Kgpper and J.Thiem, J. Carbohydr. Chem., 1987, 5, 57. M.K.Gurjar and S.M.Pawar, Carbohydr. Res. , 1987, 159, 325. S.David and A.Fernandez-Mayoralas, Carbohydr. Res., 1987, 165,C11. T-Ikekawa,K.Irinoda, K.SaZe, T.Katori, H-Matsuda,M.Ohkawa, and M.Kosik, 2894. Chem. Pharm. Bull., 1987, 3, S.Koto, N.Morishima, Y.Mori, H.TanaJca, S.Hayashi, Y.Iwai, and S.Zen, Bull. Chem. SOC. Jpn., 1987, 60, 2301. R.Nouguier and C.Medani, Tetrahedron Lett., 1987, 28, 319. T.Mikami, H.Asano, and O.Mitsunobu, Chem. Lett., 1987, 2033. O.R.Martin, K.G.Kurz, and S.P.Rao, J. Org. Chem., 1987, 52, 2922. K.Ikeda, S.Nakamoto, T.Takahashi, and K.Achiwa, Chem. Pharm. Bull., 1987, 35, 4436. R.N.Shah, J.Baptista, G.R.Perdomo, J.P.Carver, and J.J.Krepinsky, J. Carbohydr. Chem., 1987, 6, 645. M.H.Park, R.Takeda, and K.Nakanishi, Tetrahedron Lett., 1987, 28, 3823. M.Carmen Cruzado and M.Martin-Lomas, Carbohydr. Res., 1987, 170,249. M.Alonso-Lopez, J.Barbat, E.Fanton, A.Fernandez-Mayoralas, J.Gelas, D.Horton, M.Martin-Lomas, and S.Penades, Tetrahedron, 1987, 43, 1169. S .E .Denmark, R.P .Hammer, E .J .Weber, and K.L.Habennas , J. Org Chem. , 1987, 52, 165. THalmos , R.Montserret , J.Filippi , and K. Antonakis , Carbohydr Res , 1987, 170, 57.

-

. .

.

56 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41

42 43 44 45 46 47

Carbohydrate Chemistry S.Valverde, M.Martin-Lomas, and B.Herrad&, J. Carbohydr. Chem., 1987, 6, 685. F.Kong, J.Du, and H.Shang, Carbohydr. Res., 1987, 162, 217. T.B.Grindley, G.J.Reimer, J.Kralovec, R.G.Brown, and M.Anderson, Can. J. Chem., 1987, 65, 1065. R.Khan, M.R.Jenner, H-Lindseth, K.S.Mufti, and G.Pate1, Carbohydr. Res., 1987, 162, 199. C.K.Lee, Carbohydr. Res., 1987, E,53. M.M.Abdu1-Malik, Q.J.Peng, and A.S.Perlin, Carbohydr. Res., 1987, 159, 11. A.U.Rahman and M.Y.Khan, J. Pure Appl. Sci., 1986, 5, 37 (Chem. Abstr., 1987, 107, 237 155). N.K.Kochetkov, Tetrahedron, 1987, 34, 2389. G.Deffieux, R.Baute, M.-A.Baute, M.Aftani, and h.Carpy, Phytochemistry, 1987, 5, 1391 and 1395. M.V.Rao and M.Nagarajan, Carbohydr. Res., 1987, 162, 141. M-Funabashi and H.Nagashima, Chem. Lett., 1987, 2065. Y.Fang, F.Kong, and Q.Wang, J. Carbohydr. Chem., 1987, 6, 169; Erratum, 6 , 537. E.Wu, F.Kong, and B.Su, Carboh dr. Res., 1987, 161,235. P.Kov&, H.J.C.Yeh, and b r b o h y d r . Chem., 1987, 6, 423. M.Sharma, G.G.Potti, O.D.Simmons, and W.Korytnyk, Carbohydr. Res., 1987, 162, 41. J.G.Batelaan, A.J.M.Weber, and U.E.Wiersum, J. Chem. Soc., Chem. Commun., 1987, 1397. H-Takayama, A.Iyobe, and T.Koizumi, Chem. Pharm. Bull., 1987, 35, 433. M.-T.Garcia L6pez, F.G.De las H e r a s , J . Carbohydr. Chem., 1987, 6, 273. P.Ko11 and U-Lendering, J. Carbohydr. Chem., 1987, 6, 281. G.N.Austin, G.W.J.Fleet, J.M.Peach, K.Prout, and J.C.Son, Tetrahedron Lett., 1987, 28, 4741. R.Khan and G.Pate1, Carbohydr. Res., 1387, 162, 209. M.K.Gurjar, V.J.Pati1, and S.M.Pawar, Carbohydr. Res., 1987, 165, 313. P.A.McNicholas, M.Batley, and J.W.Redmond, Carbohydr. Res., 1987, 165,17. S.J.Angya1, J.D.Stevens, and L.Odier, Carbohydr. Res., 1987, 169, 151. H.Ohrui, T.Misawa, H.Hori, Y.Nishida, and H.Meguro, sric. Biol. Chem,, 1987, 51, 81. C.Z.Smith, J.H.P.Utley, and H.L.Chum, J. Chem. Res., Synop., 1987, 88 (Chem. Abstr. , 1987, 107,217 946).

6 Acetals

1.

Isopropylidene Acetals

A further paper on the determination of ring sizes of isopropylidene 13

C-n.m.r. of the acetal carbon atoms has acetals b5; means of the appeared. An improved synthesis of 1,2:5,6-di-Q-isopropylideneD-galactofuranose by means of the treatment of the enose ( 1 ) with borane in DiviS, followed by alkaline hydrogen peroxide, has been des2 cribed.

Tosic acid-catalyzed rearrangement of mono-Q-isopropylidene derivatives of aldose diethyldithioacetals has been demonstrated by labelling experiments to proceed an intramolecular process. The reactions always proceeded to yield the threo-acetal. Thus 4,5-0i s o p r o p y l i d e n e - D - a r a b i n o s e diethyldithioacetal, on treatment with tosic acid at 60' for 48 hours, gave the 2,3-g-isopropylidene derivative (2). Similar reactions with 4,5-~-isopropylidene-xylose ( 3 ) derivative gave an equimolar mixture of the rearranged 2 , 3 - and 3,4acetals, (4) and ( 5 ) . In the same way the 5,6-acetals (6) and ( 7 )

Carbohydrate Chemistry

58

gave (8) and ( 9 ) respectively. The same paper described an improved synthesis of 2,3:5,b-di-O-isopropylidene-D-glucofuranose diethyldi3 thioacetal. Treatment of D-fructose with 2-methoxypropene in the presence of stannous chloride in refluxing 1,2-dimethoxyethane gave the 1,2ace;al ( 1 0 ) . blurther reactions of ( 1 d ) Mill be found in Chapter 1 5 . ~ MeOCH NHAc

\

01

'The purification of diisopropylidenasorbose using mixtures o f benzene-petroleum instead of benzene alone results in a product with 5 greatly reduced water content. On treatment with dimethoxyyropene-tosic acid $-acetyl-0-glucosylarnine gives the two 2,3:5,6-acetals ( 1 1 ) and ( 1 2 ) in 43X and 10% 6 yields respectively. Acetonation of lactose with 2-nethoxypropene-tosic acid in UMk' has been shown to give the 4',6'-2-isoproderivatives in 54% and pylidene- and 3,2':4'01-di-0-isopropylidene 24>0 yields respectively, and not the b,2':4'6I-diacetal as p r e viously claimed (see Vol. 14, p . 4 5 ) . Studies with benail,& lsctoside revealed initial formation of the b,6'-di-Q-(methoxydlmethil)-uethyl acetal. Uses or' these observations in the synthesis 7 of macrocyclic ethers are described in Chapter 5 . 2.

Benzylidene Acetalv

A new di-2-benzylidene derivative (13) of D-arabinose diethyl dithioacetal was obtained by benzylidenation with d,d-dimethoxytoluene, 8 Its structure was confirmed by X-ray crystallography. Treatment

of 1-deoxy-I-p-toluidino-D-fructose with benzaldehyde in ethanol 9 gave, after acetylation, the 2,3-benzylidene derivative ( 1 4 ) .

59

6: Acetals

3.

O t h e r Aceta_&

' I ' e t r o s e d e r i v a t i v e s have been p r e p a r e d v i a t h e i n t e r m e d i a t e s u l p h o x i d e s o b t a i n e d by t r e a t m e n t o f 2 , 3 - g - i s o p r o p y l i d e n e - D - g l y c e r a l d e h i d e w i t h e t h y l ethylthioliiethyl sulphoxide (15 ) . 'thus l i t h i u m aluniiniuili h i d r i d e r e d u c t i o n o f t h e 0 - e r y t h r o - s u l p h o x i d e s

g a v e 3,4-9-

i s o ~ r o ~ ~ l i d e K l e - u - e ~ ~ t hd ri eotshej r l d i t h i o a c e t a l s ( 1 6 ) and ( 1 ' 1 ) a n d

trie same s u l p h o x i a e w i t h t r i p h e , l l p h o s p h i n e - c a r b o n t e t r a c h l o r i d e i s o m e r s ( 18 ) . Keaction o f 3,4-g-thionocarbonyl-

i5

gave t h e 2-ChlOrO

( 1 9 ) w i t h t r i b u t y l t i n h y d r i d e h a s been i n v e s t i g a t e d t h e p r o d u c t s f o u n d was t h e m e t h y l i d e n e a c e t a l ( 2 0 ) which becaine t h e major p r o d u c t when a n e x c e s s o f t h e t i n r e a g e n t was 11 12 used. lJew a c e t a l s o f adenine n u c l a o s i d e s a r e described i n

,5-L-arabinoside in detail.

Amon,

I

0Ac

OAC

(19) C h a p t e r 20.

(20)

D i a s t e r e o s e l e c t i v e c y c l o p r o p a n a t i o n of 1 , 4 - d i - g - b e n z y l -

i - t h r e i t o l k e t a l s o f 2-cycloalken-1-ones

using chelation-controllad

r e a c t i o n s h a s been shown t o be a g e n e r a l p r o c e d u r e . hex-2-enyl

a c e t a l ( 2 1 ) gave a Ij:l

a t i v e s ( 2 2 ) a n d (23) (Scneme 1 ) .

13

Thus t h e c y c l o -

r a t i o of t h e c y c l o p r o p a n e d e r i v -

Scheme 1

1,Z-g-Cyanoethylidene

d e r i v a t i v e s of a l k y l marinopyranuronates have

been s y n t h e s i z e d v i a J-ones o x i d a t i o n o f t h e c o r r e s p o n d i n g 1,2-2c y a n o e t h y l i d e n e mannogyranoues (Scheme 2 ) .

74

Referent+ t o a c y c l i c a c e t a l s a t t h e a n o m e r i c c e n t r e w i l l be f o u n d

60

Carbohydrate Chemistry

i n Cnapter 3 .

Reag".ts

:

-

L, N d M e MeOH ;ii,TrCL- Py ;'G, CrOJ ; W , BnOH

Scheme 2

S y n t h e s i s o f two i s o m e r s o f t h e s p i r o - o r t h o l a c t o n e

p a r t of t h e

C-D f r a g m e n t o f o r t h o s o m y c i n s h a s b e e n d e s c r i b e d (Scheme 3 ) . 1 5

References

1

fi.S.H.El

103, 262.

L

3

4

5 0

7 d Y

1U

11 12

13 14

15

A s h r y , Y.E.Kilany,

a n d A.iiioussad,

Carbohydr.

&,

1987,

C;.Liu a n d L.Hu, Wu.ii Huaxue, 1980, L, 118 (Chem. A b s t r . , 1Yb7, 1 0 7 , 217 3 4 7 ) . T . S . t i r i n d l e y a n d C.Wickrarnage, C a r b o h y d r . k, 19b7, ,&7, 105. L.ben D r i j v e r , C.W.Holzapfe1, rl.S.Van Dyk, a n d L . J . K r u g e r , C a r b o h y d r . h, 1987, ki, 05. Y a . d a l i n o v a n d I . I v a n o v , lihim. I n d . ( S o f i a ) , 1960, 2 , 443 A b s t r . , 1 4 1 7 , &7, 134 5b6). lvi.Galicio, S . d . C a n g i a n i , ~ l . E . t i e i p i , a n d K.A.Cadenas, An. Asoc. uuini. A r g e n t . , 1Y8b, 3, 3u3 (Chem. A b s t r . , 1 9 8 7 , 1 2 ,67 603). I\i.Alonso-Lopez, J . B a r b a t , E.k'anton, A.Fernandez-iVlayoralas, J.belas, L). H o r t o n , ivi.lviartin-Lomas, a n d S . P e n a d e s , T e t r a h e d r o n , 196'7, ,%, 1109. T . B . t i r i n d l e y , S.Kusuma, T.S.Cameron, a n d A.Kumari, C a r b o h y d r . &, lY87, 2 ,1 7 1 . I . F . S t r e l ' t s o v a , 2.Altad. Nauk K i r g . SSR, 146b, 43 A b s t r . , 1 4 8 7 , i s , 136 695). J.A.Lopez S a s t r e , A.Sanz T e j e d o r , J . P . R o d r i g u e z Amo, J.D.lolina M o l i n a , Quirn., S e r . C , 1986, b2, 1 4 0 (E. and 1 . I z q u i e r d o Cubero, A b s t r . , 1 9 6 7 , u 7 , 217 93Y). K.Kanemitsu, Y.Tsuda, ~ I . E . H a q u e , K.Tsubono, a n d T . K i k u c h i , 3. Pharm. dull., 14b7, g ,3 6 7 4 . V.baKthavachalam, L.-C;.Lin, X.lfi.Cherian, a n d A.w.Czarnik, C a r b o h y d r . &, 1467, E, 1 2 4 . r.A.Mash a n u K . A . h e l s o n , T e t r a h e d r o n , l 9 b 7 , 079. V . I . & e t a n e l i , A . Y a . U t t , O.V.firyukhanova, a n d ~ . K . K o c h e t k o v , B i o o r g . 1085 (Chem. A b s t r . , 1987, U 7 , 148 8 i O ) . Khim., 1980, l-2, J.-h.Beau, b . J a u r a n d , J . E s n a u l t , a n d P . S i n a y , T e t r a h e d r o n L e t t . ,

(w.

(w.

&.

s,

ircr7.

L&.

llu5.

7 Esters 1

General Methods

Guanidine has been used for the very rapid deacetylation of sugar peracetates quantitatively; benzoyl and pivaloyl groups were un1 affected. Peracetylated sugars, on treatment with tributyltin methoxide, gave products selectively deacetylated at the anomeric centre. Equatorial anomers were deacetylated more quickly, and 2 hence selectively, than their aiial counterparts. Lipases obtained from the porcine pancreas and Candida have been used to remove ester groups selectively; the 3-Q-acetyl derivative of 1, 2: 5,6-di-~-isopropylidene-d-D-glucose was removed by the former but not the latter, while the butanoyl group was removed by both. Candida lipase was found to remove selectively the 6-0-acetyl group from methyl 2,3,4,6-tetra-Q-acetyl-o(-D-giucopyranoside and the 5-0butanoyl group from 3-~-acetyl-1,2-~-isopropylidene-5-~-butanoyloc-D-xylofuranose. Secondary debutanoylation was also achieved on 5-~-2,2-dimethylpropanoyl-l,2-O-isopropylidene-~-~-butanoyl-~-D-xylofuranose using Candida l i p a ~ e . Reversal ~ of the normal action of lipases has been achieved in dry organic solvents when selective acylations at secondary positions were possible .4 Dibutylstannylidene acetal activation of the 2,b-dideoxy-hexopyranosides (1) - ( 3 ) has been used to acylate, sulphonylate, o r alkylate the 3-position regioselectively. Various esterolytic enzymes have been in-

OH

vestigated for carrying out partiai deacetylation of 1,6-anhydro2,3,4-tri-~-acetyl-~-L)-glucopyranose; chymotrypsin and wheat germ lipase preferen'tially removed the 0-3 acetyl group whereas liver esterase and pancreas lipase selectively removed the acetyl group from 0-4 thus providing an improvement over regiochemical 6 Among many examples of alcohol acylations with acid methods. anhydrides under cobalt(I1) chloride catalysis is a report of the

62

Carbohydrate Chemistry

p e r a c e t y l a t i o n o f U-glucose i n 95X y i e l d . The r e a c t i o n , c o n d u c t e d 0 7 a t 80 C , c o u l d n o t be u s e d f o r s e l e c t i v e a c e t y l a t i o n . 2

Carboxylic E s t e r s

H i g h l y p u r i f i e d I j - a c e t y l - 4 - ~ - a c e t y l n e u r a m i n i c a c i d (Neu 4 , 5 Ac ) ,

2 a n d lJeu 5 , 7 , 9 Ac have been u s e d t o s t u d y spon2' 3 t a n e o u s m i g r a t i o n s o f a c e t y l groups between hydroxy g r o u p s. A t pH

d e u 5 , 7 Ac

v a l u e s where d e a c e t y i a t i o n d o e s n o t t a k e p l a c e i t was shown t h a t lJeu j , 7 Ac was e a s i l y c o n v e r t e d i n t o Neu 5 , 9 Ac a n d lieu 5,'7,9 Ac 2 2' 3 y i e l d e d a n e q u i l i b r i u m arnourit o f lieu 5 , 8 , 9 Ac w h i l e Neu 4 , 5 Ac

3'

did not give r i s e t o migrations.

f o r t h e b i o s y n t h e t i c o r i g i n s or' 2 - a c e t y l a t e d a c i a and 2 - g l y c o l y l n e uraminic

2

The r e s u l t s a r e o f s i g n i f i c a n c e s i a l i c acids.

8

Sialic

a c i d have been shown t o be e s t e r i f i e d

a t t h e 9-hydroxy g r o u p u s i n g o r t h o e s t e r s and c a t a l y t i c t o s i c a c i d ; s e l e c t i v e 9 - e s t e r i f i c a t i o n was a l s o a p p l i c a b l e t o I J - a c e t y l 04- a n d 'The same p a p e r r e p o r t s t h e s y n t h e s i s

p-neuraminyl-oligosaccharides.

o f ~ + - ~ - a c e t y l - ~ - a c e t y i n e u r a m i n iacc i d .

9

An improved p r o c e d u r e f o r t h e s y n t h e s i s o f s u g a r monochloroa c e t a t e s u s e s m o n o c h loroacetic anhydride-sodium i n DPlr' a s r e a g e n t m i x t u r e .

hydrogen c a r b o n a t e

The e s t e r s , o b t a i n e d i n up t o 88W y i e l d ,

were u s e d i n f u r t h e r c h l o r o - s u b s t i t u t i o n

r e a c t i o n s t o form, e.g.,

10

aeidoacetates. The 1-Q-acyl g r o u p i n 1 , 2 - t r a n s - a c y l a t e d a l d o s e s h a s been r e p l a c e d by t r i f l u o r o a z e t y l by h e a t i n g w i t h t r i f l u o r o a c e t i c anhydride-trifluoroacetic a c i d . F u r a n o s e s g a v e e i t h e r p-anomurs o r m i x t u r e s o f A- and j3-anomers,

w h e r e a s p y r a n o s e s gave o n l y d - a n o m e r s .

d j r d r o l y s e s g i v i n g t h e I - h y d r o x y d e r i v a t i v e s p r o c e e d e d i n good yields.

11

The s u s c e p t i b i l i t y o f m e t h y l 2 , 6 - d i - ~ - p i v a l o y l - a - U - g l u c o p y i - a n o s i d e t o e s t e r a s e s from r a b b i t s e r a h a s been e x a m i n e d ; t h e 6 - e s t e r g r o u p was h y d r o l j z e a much more r e a a i l y . g r o u p o f oc-U-glucose

12

'lhe prirnary hydroxy

and methyl a<-0-glucopyranoside

were s e l e c t -

i v e l y e s t e r i f i e d by t r e a t m e n t w i t h N - a c y l t h i a z o l i d i n e - 2 - t h i o n e s ( 4 ) i n pyridine-lhS0 ( f r e e sugar) o r pyridine alone ( g l y c o s i d e ) . Y i e l d s 01' e s t e r s were g r e a t e r t h a n 6 w X .

j i , R-C-N

13

R = Me(CH2),-

,q=6-16

S

LJ (4) 2,3,4-Tri-~-acyl-U-glucoses have been f o u n d a s l i p i d components i n t h e l e a v e s o f t h e tomato Lycopersicon p e n e l l i . Nine compounds

7: Esters

63

were i s o l a t e a , t h e a c y l i n o i a t i e s b e i n g p r i m a r i l y 2-methylpropcinoyl 2-methylbutanoyl,

3-met1iylbutanoy1, d-metnylnorianoyl

and decanoyl.

14

'l'he s y n t h e s i s o f s u c r o s e a n u r n a n n i t o l p o l y s t e a r i c a c i d e s t e r s using a solvent-free

system h a s been d e s c r i b e a ,

K i z z i rnethod o f t r a n s e s t e r i f ' i c a t i o n

i n which a inodifidd

by e t h y l s t e a r a t e i s e i n p l o y e d .

The m e t h o d , w i t h p o t a s s i u r n s o a p a s s o l u b i l i z e r a n d s o d i u i n - p o t a s s i u r n a l l o y a s c a t a l y s t , was c a r r i e d o u t i n a o n e - p o t 15 y l e i d s o f up t o 9 5 ~ .

?rocedure, giving

~ J o v e l~ ' - i L ) - O - p - c o u m a r o y l - ( 5 ) a n d - f e r u i o y l - ( 6 1 - ~ a l a c t a r i c a c i d s h a v e b e e n i s o l a t e d r ' r o n o r a n g e peel.

16

dew a c y l a t e d f l a v o n o l

X

0

HO

I O H C02H

(5) X = H

(6) X = O M C

g l u c o s i d e s h a v e ueen i s o l a t e d f r o u l e a v e s o f H l l i u i n t u ' o e r o s u n , a n d shown t o c o n t a i n 2 - U - ~ s r u l o y l - ~ - U - ~ l u c o p ~ r a f l o s i m d eo i e t i e s .

'ihe

r n i g r a t o r y p r o p e n s i t y o f t h e f e r u l o y l ,.rout, f r o m 0 - 2 t o 0-0 was 0 17 d e m o n s t r a t e d a t pd 7 , I O U C o r a t pH 1 1 a t r o o m t e m p e r a t u r d . An i m p r o v e d s y r i t h e s i s o f c o r d f a c t o r a n a l o g u e s via t h e i d i t s u n o b u r e a c t i o n u s e d t r e h a l o s e w i t h tripheuylphosphine-diisopropylazo-

aicarboxylate-P-G-tetrahyuropyran-2-yl

mycolic a c i d anu t r i s ( d i -

methy1amino)phosphine oxide-aichloronethane a s s o l v e n t .

u,G'-Ui-

m i c o l y l t r e n a l o s e was o b t a i n e d i n z o o d y i e l a u n d e r t h e s e m l i d c o n d i t i o n s i n which t h e r e i s no p r o t e c t i o n o f t n e c a r b o h y d r a t e required.

13

Two g r o u p s h a v e c a r r i e d o u t d i a s t e r e o s e l e c t i v e b i e l s

Alder r e a c t i o n s on s u g a r a c r y l a t e e s t e r s a s c h i r a l a u x i l i a r i e s

via titanium -

c o r n p l e x e s a s snown i n Scheme 1," o r uncatalyzea 2u w i t h a r a n g e o f a i e n e s , e . g . , a s show11 i n Sche:ne 2 . Arylgropanoic

TM SO CH2

major isomer (97%)

(Post-)'

R q d : i,

Ti&+-CHZCly

(-70O);'&,

Q ,(-70']

Scheme 1

e s t e r s o f d i - and m o n o - a c e t o n e

g l u c o s e have been prepared i n a n

Carbohydrate Chemistry

64 o p t i c a l l y puce s t a t e .

Hydrolysis o r t r a n s e s t e r i f i c a t i o n of the

products yielded t h e o p t i c a l l y pure arylpropanoic a c i d s , o r t h e i r nethyl esters. propyl-phenyl,

Aryl groups used were 3-fluoro-diphenyl, 2-methyl21 Perbenzoyl-P-D-

and b-methoxynaphth-2-yl.

g l u c o p y r a n o s y l c i n n a m a t e h a s been p r e p a r e d from t h e c o r r e s p o n d i n g 22 gljrcosyl bromide u s i n g phase t r a n s f e r c a t a l y s i s . The e s t e r g l u c u r o n i d e ( 7 ) o f d i f l u n i s a l was f o u n d t o b e u n s t a b l e p a r t i c u l a r l y i n n e u t r a l o r b a s i c s o l u t i o n , nine rearrangement o r d e g r a d a t i o n p r o d u c t s b e i n g d e t e c t e d by r e v e r s e d - p h a s e

HPLC. 2 3

ion-pair

The f u l l p a p e r o n h e t e r o g e n e o u s c a t a l y t i c t r a n s f e r h y d r o -

F

C0z-p- D-GLcAp

g i n o l y s e s o f c o n f o r m a t i o n a l l y r i g i d m o l e c u l e s i n which b e n z y l groups a c t a s h y d r o g e n d o n o r s t o y i e l d b e n z o a t e e s t e r s ( s e e Vol. Z U , p . 7 1 ) has appeared.24

F u r t h e r s t u d i e s on t h e s e l e c t i v e e s t e r i f i c a t i o n of

m e t h y l 4,b-di-g-benzyl-d-D-mannopyranoside h a v e b e e n r e p o r t e d ( s e e Vol. 20, p . 6 8 ) .

W i t h b e n z o y l c h l o r i d e o r t o s y l c h l o r i d e i n t h e two

phase system, benzene-aqueous s o d i u m benzenesulphonate-DlvlSO,

sodium h y d r o x i d e , the 2-esters

a c y l a t i o n a t 0-3 was a c h i e v e d by e m p l o y i n g s u b s t r a t e i n THF.25

i n t h e p r e s e n c e of

were o b t a i n e d . 3

Selective

copper complex o f t h e

The m e t h y l g l y c o s i d e ( 8 ) o f c u r a c i n , t h e

c h r o m o p h o r i c t e r m i n u s of s e v e r a l o r t h o s o m y c i n a n t i b i o t i c s , h a s b e e n synthesized conventionally. 26 prepared.

The 3 - 2 - a c y l a t e d

r e g i o i s o m e r was a l s o

A new e l l a g i t a n n i n , l i q u i d a m b i n , f r o m t h e l e a v e s of L i q u i d a m b a r

7: Esters

65

f o r m o s a n a , h a s been i d e n t i f i e d as 5-Q-galloyl-2,3:4,6-di-O-(S)-

hexahydroxydiphenoyl-b-glucose, w h i c h h a s a f r e e a l d e h d o g r o u p , present i n t h e hydrated f o r n t o a s u b s t a n t i a l extent.'?

Ellagi-

t a n n i n s possessing a dimeric s t r u c t u r e with s e v e r a l g a l l o y l groups c o r i a r i i n A ( 9 ) , d i s p l a y Ioarked a n t i -

on t h e g l u c o s e c o r e , e . g . ,

t u u o u r a c t i v i t y , a p p a r e n t l y by p o t e n t i a t i o n o f t h e i m m u n i t y o f t h e L6 1 1 host. U e t a i l e d s t u d i e s u s i n g 2 U I l l - d a n d H-"G n.iu.r.

co-0

GE

G = GcxUOyL

OH

s 9 e c t r o s c o p j h a v e d e m o n s t r a t e d t h e o l i g o r n e r i c n a t u r e or' s e v e r a l coinplex g l u c o s e - c o n t a i n i n g

tannins

."

kcyl ortho-esters

undergo a f a c i l e rearrangement t o trans-diacyl ( 1 1 ) by a n i r i t r a m o l e c u l a r

of t n e retro-ene

reaction.

( 1d )

d e r i v a t i v e s of t y p e

e r i c y c l i c t r a n s i t i o n s t a t e similar t o t h a t 50

S e l a c t i v e a d d i t i o n of t h e p r i m a r y h y d r o x j g r o u p 0 2 u - g l u c o s e , g a l a c t o s e , dnd m e t h y l r i - u - g l u c o p y r a n o s i a e

D-

t o a l l y 1 i s o c j a n a t e s gdve

t h e c or r a s pond i n g 6 - g - c a r ba l u o y l - d e r i v a t 1 v e s

'

.

k i i i t ! ~t h e

d i s a c c-

h a r i d e g i y c o s y l c h l o r i d e ( 1 L ) r e a c t e d w i t h t h e auiiilo a c i d d e r l v -

a t i v e ( 1 3 ) an unexpected m i g r a t i o n o f t h e cdrbamate p r o t e c t i n g Lroup 32 o c c u r r e d t o g i v e t h e g l y c o s j l u r e t h a n e ( I + ) , dcheme j .

S y n t h e t i c r o u t e s l e a d i n g t o g l y c o p e p t i d e s have been r e v i e w e d ; i t was c o n c l u d e d t h a t t h e e a s i e s t a p p r o a c h t o t h o s e c a r r y i n g a c l u s t e r

Carbohydrate Chemistry

66

o f m o n o s a c c h a r i d e u n i t s was t o u s e t h e a c t i v e e s t e r method w o r k i n g s t e p w i s e from t h e C-terminus. The u s e o f EEUQ o r DCC was recommended f o r t h e more c o m p l e x g l y c o p e p t i d e s 3 3 k o n o s a c c h a r i d e - m o d i f i e d

.

t u f t s i n s a n d r i g i n s h a v e b e e n p r e p a r e d by g l u c o s y l a t i o n o f t h e da m i n o f u n c t i o n , a m i d a t i o n o f t h e c a r b o x y l g r o u p w i t h 2-amino-2-deoxy/?-D-glucopyranose,

Q-glucosylation

of t h e threonine hydroxy group and

g l y c o s y l a t i o n o f t h e g l u t a m i n e s i d e c h a i n amido group. t h e s y n t h e s i s o f H-Gly-Glu( I i d C l c ) -Pro-Arg-OH

A scheme f o r The

was g i v e n . 34

s y n t h e s i s of ~-(2-acetamido-2-deoxy-D-glucopyranuronos-3-yl)-~-lactoylL-alanyl-D-isoglutamine

h a s been accomplished i n s e v e r a l s t e p s from

b e n z y l ~-acetyl-L+,6-Q-benzylidene-d-Il-muramic a c i d b e n z y l e s t e r . lteference t o t h e antiturnour glycoside ( - ) - p h y l l a n t h o s t a t i n , C-1

e s t e r , i s made i n C h a p t e r l y .

35

a

Placrocyclic e s t e r s (15) i s o l a t e d

f r o i n t h e r o o t o f Ipomoea o r i z a b e n s i s , h a v e ( l l ~ ) - h y d r o x y p a l m i t i c

a c i d a s b o t h a n a g l y c o n i c and a n e s t e r g r o u p on a t e t r a s a c c h a r i d e .

(15)

Me

@

36

R’ = 3 - h y d n > x y - 2 - m e t h y L - b ~ a n o y l R3 = R’, 2-rn&kyLpropanoyL, 2 - meLhgl-buLan-oyL

R3 o

OH

Japanese workers have c o n t i n u e d t h e i r comprehensive i n v e s t i g a t i o n s i n t o s j n t h e s e s o f l i p i d A a n d r e l a t e d compounds. A review of t h e s t r u c t u r e a n d t o t a l s y n t h e s i s o f S a l m o n e l l a l i p i d A h a s a p p e a r e d . 37 Analogues o f t h e non-reducing s u b u n i t of b a c t e r i a l l i p i d A have been s y n t h e s i z e d i n c o n v e n t i o n a l manner t o s t u d y t h e i r s t r u c t u r e - a c t i v i t y profile

.38-40

0

CH20H

p - s n,

cy

- o P(O](OH),

A r e l a t e d compound l i p i d X ( 1 6 ) (ti

1

’7)

2

=R =CH CH(OtI)(CH )

Me,X=

2 10

OP(0) ( O H ) ) h a s b e e n s y n t h e s i z e d a s i t s tris~hydroxymethyl)amino2

67

7: Esters

m e t h a n e s a l t by t r e a t m e n t o f 2-amino-2-deoxy-0-glucose w i t h t h e succinimide d e r i v a t i v e (17) followed conventional manipulations.

42

b ' u r t h e r d e t a i l s o f t h e s y n t h e s i s o f l i p i d X a n d s i m i l a r compounds p r e v i o u s l y r e p o r t e d ( s e e Vol. 1 5 , p.71 a n d Vol. 20, p . 7 2 ) h a v e b e e n 43-45 hieference t o t h e g l y c o s i d a t i o n s o f s y n t h e t i c

published.

l i p i d X analogues t o give various disaccharides related t o l i p i d A i s Inade

i l i

thesized

Chapter 3.

via

'I'ne P r o t e u s m i r a b i l i s l i p i d A h a s b e e n s y n -

a versatile intermediate disaccharide

( 1 8 ) b e a r i n g two

amino a n d s i x h y d r o x j groups e a c h cheinically d i f f e r e n t i a t e d .

4b

S y n t h e s i s o f immunoinodulators w h i c h c o m b i n e t h e s t r u c t u r e s o f l i p i d A a n a I-aeoxy-niuramyl

d i p e G t i d e l i n k e d t o a s p a c e r a r u h a s been

accompiished, i n order t o e x p l o i t t h e discovery t h a t l i p o p h i l i c d e r i v a t i v e s o f 1 -deoxy-murainyl

d i p e p t i d e showed s t r o n g iinmurioad j u v a n t 47 20, p.176).

and a n t i i n f e c t i v e a c t i v i t y ( s e e Vol. O-CHz

~

~

n

o

@

-

(18)

R - C1C ,

CMe20co-,

NHR

NH2

3

o

Phosdhate and iielated b s t z r s

via

The s y n t h e s i s o f glycosyl p h o s p h a t e s mono- a n d o l i g o - s a c c h a r i d e s

O-acetgl-U-6alactopyranose

lithium s a l t s of acetylated

h a s been d e s c r i b e d .

Thus 2 , 3 , 4 , 6 - t e t r a -

and d i b e n a y l d i p h o s p h a t e i n t h e p r e s e n c e

of' b u t y l l i t h i u n i ~ a v et h e p y r a n o s y l d i b e n z y l p h o s p h a t e w h i c h was h y d r o -

genolyzed and t r e a t e d with l i t h i u m hydroxide t o y i e l d t h e P - g a l a c t o s y l phosphate.

'The r e a c t i o n was a l s o s u c c e s s f u l w i t h t h e o l i g o s a c c h a r i d e s

12ha-Gal a n d han-iiha-Gal .48

Coilventional methods nave been used t o

c o n v e r t 1,2-l)-alKylidene-&-ll-glucofuranose

3,j,b-bicyclophosphites

i n t o t h e b i c y c l o p h o s p h a t e s and t h e i r thiophosphono and selenophosphono analogues.

''

$-Acetylgalactosaminyl

phosphates, prepared

via

a n d ;-ace

tylglucosaminyl

p h o s p h o r y l a t i o n o f t h e a p p r o p r i a t e mono-

s a c c h a r i d e p e r a c e t a t e s , h a v e b e e n t r e a t e d w i t h m o r a p r e n y l phosphoimidazolide t o give t h e corresponding glycosyl moraprenyl diphosphates. " d-D-glucose

D i p h o s p h o n a t e t r e a t m e n t o f o(-D-glucose

1- p h o s p h a t e

gave

1-phosphonylphosphate without concomitant phosphonylation

of t h e r e m a i n i n g hydroxy g r o u p s . 51

Ketose phosphate d e r i v a t i v e s

h a v e b e e n p r e p a r e d by a l d o l a s e m e d i a t e d c o n d e n s a t i o n s o f 3 - d i h y d r o x y p r o p a n o n e a n d L-

o r D-glyceraldehyde.

High y i e l d s o f D-fructose

and

68

Carbohydrate Chemistry

52 L-sorbose 1-phosphates were obtained. Careful monitoring of' tne reaction of monothio-acids of phosphorus (ly), with j , 6 - a n h y d r o - l , ~ - ~ - i s o p r o p y l i d e n e - d - u - g l u c o f u r a n o s e has given a deeper insight into the mechanism of the reaction. New convincing arguments have been adduced for the participation of a peatacoordinate intermediate in the transphosphorylation step leadinn from the thiophosphate ( 2 ~ ) )to the ~-phosphoryl-6-thioglucose (21).3 7

Authentic phosphates of hU0, 3-deoxj-U-arabino-heptulosonic acid and 3-deoxy-U-glucooctulosonic acid were converted into methylated derivatives suitable f o r g.c.-m.s. as a n aid to the detection of such

''

phosphates in lipopolysaccharides and related biomaterials. 'l'he thiophosphonamido derivative ( 2 2 ) has been prepared by reaction or' P(1kEt ) with N,N-dimethyl-0-gluconamide followed by treatment witn 'fne structure das established by an &-ray crystallographic sulph;r? 53 study

.

$ONMe2

A high yiela synthesis of carbon-labelied intermediates of the Lpentose pathway has been reported. Enzymic synthesis was used to prepare "C-labelled octulose mono- and biphosphates and sedoheptuiose 1 ,?-biphos?hate f r o m 1 ,j-dihydroxypropanone phosphates and 4Clabelled aldopentose %-phosphates and erythrosa 4-phosphate respectively (see also ref. 5.2 above). A similar enzymic condensation of P-hjdroxypjruvate with "C-labelled aldohexose 6-phosphate gave Dlycero-lJ-ia-octulose 8-phosphate. 'I'ne paper a l s o aescribes the syn14 thesis of U-i LJ-14C]-arabinose 5-ghosphate r'roiu U-lU- C ] glucosarfline >b b-phosphate by reaction with ninhydrin. 'l'he disaccharide d-U-ivlanp( - 1 +L)d-D-igianp-ONe has beer1 converted by standard methodology to 6- and O ~ - D O I ~ O - and b,6'-di-phosphate deriv-

7: Esters stives.

57

o'-Phosphates

o f 4-1,j-

and 1,6-linked

j l y c o s i d e s o f methyl 9-hydroxyrionanoate

Iriphenylphosphine-di-isopropyl

mannose a i s a c c h a r i d e 58

have l i k e w i s e been prepared.

a z o d i c a r b o x y l a t e t r e a t m e n t or' s u c r o s e

t e t r a a c e t a t e - g a v e b i s p h o s p h i n a t e ( 2 3 ) whose s t r u c t u r e was c o n f i r u e d 13 54 by "P a n d C-11.m.r. spectroscopy. U i g l y c o s y l p h o s p h a t e d e r i v a t i v e s l i n k i n g a r a b i r i o s e t h r o u g h phosp h a t e t o s u c r o s e o r f r u c t o s e , which a r e d e r i v a t i v e s OP a g r o c i n o p i n s A and B r e s p e c t i v e l y ,

h a v e b e e n s y r i t h e s i z e a by r e a c t i o n o f t n e f r e e 3-

h y d r o x y g r o u p s o f t h e f r u c t o s e u n i t w i t h t h e ethylammonium s a i t o f benzyl ~,~+-d-benzylidene-ci-L-arabinopyranoside ,2-(2-trichloroethyl)phosphate.

''

Linkage o f oc-D-giucopyranosyl

a n d A-U-mannopyranosyl

phosphates t o g i v e ( 1 4 ) - l i n k e d g l y c o s y l phos2hosugars h a s been achieved using the p n i t r o p h e n y l 6-unsubstitutea glycoside with tne 01 01' DCC:. 'I'erroinal 6 " - p h o s p h a t e s

g l y c o s y l phosphate i n t h e presence ( I + 2 ) -d-d-ivlanp-

o f d-li-klanp(

1 +j 1- d - b - m n ,

( 1 + L ) -k-d-idlan,

a n d d-u-ivianp-

( I + d ) -K-i)-idlanp-

d-U-rvIaanp- ( I +2)-d-O-~.lanp( I + b ) -d-l)-naa,

eiicl g r o u p s o n t h e h i g h mannose o l i g o s a c c h a r i d e

e n z y m e s , h a v e b e e n s y n t h e s i z e d y&

present a s

c n a i n s ol' i y s o s o i n a l

g i y c o s i d a t i o n of t h e O-diphenyl-

p h o s p n a t e o f L ,3 , ~+-tri-~-acetyl-oc-b-rnanriopyranosyl

bromide w i t h t h e

a p p r o p r i a t e f r e e h y d r o x y d e r i v a t i v e o f t h e mannose d i s a c c h a r i d e .

b,2

'ihe s y n t h e s i s o f d o l i c h y l p h o s p h a t e s from a t e t r a s a c c h a r i d e o b t a i n e a from i u a n n o s i d o s i s - a f f e c t e d 4,

c a l v e s i s r e f e r r e d t o i r i Chapter

a n d i r i o s i t o l p h o s p h a t e s a r e c o v e r e d i n C h a p t e r 16.

i n o s i t o l 1,4,5-tri$hosphate

T r e a t m e n t 02

w i t h a w a t e r s o l u b l e c a r b o d i i m i d e gave 65

t h e 1 , 2 - c y c l o p h o s p h a t e - . ~ + ,5 - d i p h o s p h a t e .

4

S u l p h o n a t e h s t e r s arld D e r i v a t i v e s

'l'he p a r t i a l t o s y l a t i o n o f m e t h y l d- a n d j 3 - L - a r a b i n o p y r a n o s i d e 'the o r d e r or' r e a c t i v i t y was i'ound 04 a n d 3*4>2 f o r t h e o(-anomer.

been s t u d i e d . p-giycoside

!hi1 " G - n . r ~ ~ . r .

''

ii

and - g a l a c t o p y r a n o s i d e s

s t u a y oi' t h e mechanisiu

e c t i o n of' p - t o l u e n e s u l p h o n a t e t H e -p - t o l u e n e s u l y h o n y l

act: f'arffied.

has 1.01-

the

d a t a L o r b o t h p a i r s o f anoraers or' t h e t o s y l a t e s

a n d d i t o s y i a t e s o f m e t h y l L)-gl.ucocoiiectea.

t o be 2 7 3 > 4

01'

has teen

the photoiytic deprot-

e s t e r s i n b a s i c rnathanoi s u g g e s t s t h a t

r a d i c a l and t h e alkoxiae o f t h e parent a l c o h o l

' l ' e r t ' i a r y ainirle b a s e s w e r e l'ouriit t o be b e t t e r p r o m o t e r s ou

o f trie r e a c t i o n t h a n sodiuin hyUroxi.de.

5ome j - G - s u l p h a m o y l d e r i v a t i v e s o f g l u c o f u r a n o s e h a v e b e e n p r e p a r e d by r e d u c t i o n o f t h e c o r r e s p o n d i n g 3 - a a i d o s u i p h a t e s u s i n g 0' I e i t h e r s o d i u m b o r o h y d r i d e o r hydrogen-Adams c a t a l y s t .

70

Carbohydrate Chemistry

I

S e l e c t i v e t o s y l a t i o n o f 2,3-~-isopropylidene-~-ll-fructopyranose w i t h one e q u i v a l e n t

o f r e a g e n t i n p y r i d i n e y i e l d e d 552 o f t h e 5-

t o s y l a t e , w h i l e t h e 1,2-Q-isopropylidene-analogue t o s y l a t e a s t h e major product.

gave t h e 4,5-di-

d i t h 2,3-g-isopropylidene-oc-L-sorbo-

furanose and f o u r e q u i v a l e n t s of t o s y l c h l o r i d e t h e major product

(75%) was t h e 1 , 6 - d i t o s y l a t a . chloride.

68

S i m i l a r r e s u l t s were found w i t h mesyl

idiethanesulplionate d e r i v a t i v e s o f 1,2-Q-isopropylidene-

d-u-glucofuranose

have been used a s c h i r a l a u x i l i a r i e s i n e n a n t i o -

s e l e c t i v e m e t h y l a t i o n of g l y c i n e - r e l a t e d

enolates.

04

S u l p h a r o a t e d e r i v a t i v e s ( 2 4 ) a n d ( 2 5 ) o f 2,j:4,5-di-Q-isopropylidene p-D-fructopyranose

have been d e s c r i b e d . The f r e e s u l p h a m a t e ( 2 4 1 , w h i c h shows p o t e n t a n t i c o n v u l s a n t a c t j v i t y , was f o u n d , f r o m n . m . r . a n d n-ray- c r y s t a l e v i d e n c e , t o p o s s e s s a

CH20.SO, NR2

0

S

--4

t w i s t boat conformation.

70

(24) R - H

(25)R = Me

t i e f e r e n c e t o s e l e c t i v e t o s y l a t i o n o f m e t h y l 4,0-di-Q-benzyl-0(-Um a n n o p y r a n o s i d e i s made a b o v e ( r e f . 2 9 ) . j

Other h s t e r s

h l u a n t s coinposed o f a q u e o u s b o r a t e - p o l y o l s e v e r a l mono- a n d d i - s a c c h a r i d e

combinations,

including

and s u g a r a c i d b o r a t e s , have been

s t u d i e d f o r use i n t h e anion-exchange chromatography of inorganic 71 ,'I2 A s t u d y h a s b e e n made o f t h e i n c r e d s e d a b i l i t i e s o f a

anions.

number o f p o l y h y d r o x y c a r b o x y l a t e s

t o c o o r d i n a t e calciclm i n a q u e o u s 'I 3

a l k a l i n e s o l u t i o n when b o r a t e was a d d e d .

f i e a c t i o n o f 3,4-~-thionocarbonyl-~-L-arabinoside( 2 6 ) w i t h t r i P u t y l t i n h y a r i d e ( s e e Vol. 2 0 , 9.80) h a s b e e n i n v e s t i g a t e d i n d e t a i l . l h e major expected p r o d u c t s

( 2 7 ) a n d ( 2 8 ) w e r e a c c o m p a n i e d by m i n o r

smounts o f t h e i s o m e r i z e d p r o d u c t s (23) and ( 3 0 ) , t h e c y c l i c c a r b o n a t e (31) and the methylidene a c e t a l ( 3 2 ) .

Excess of t h e h y d r i d e gave

( 3 2 ) a s t h e m a j o r p r o d u c t , w h e r e a s i f a i r was b u b b l e d i n t o t h e r e a c t i o r nixture,

t h e s o l e p r o d u c t was t h e c a r b o n a t e ( 3 1 ) . r ' 4

'the r e a c t i o n of

tnionocarbonaLes w i t h methyl i o d i d e and 2,3-epoxypropane f u r t h e r i n v e s t i g a t e d ( s e e V01.20, p . 8 0 ) . :orresponding

carbonate, but with t h e 5,b-thionocarbonate

iodo-5-thionethylcarbonate

has been

Usually the prodict i s the

( 3 4 ) w8s o b t a i n e d .

75

( 3 3 ) t h e 6-

71

7: Esters

1 , 2 - ~ - ( l - e ~ o - C y a n o e t h y l i d e n e ) - ~ - ~ - a r a b i n o f u r a n o sand e l,2-g-[t~<-(lexo-cyano)benzylidenel-6-l-arabinofuranose on s t o r a g e i n c h l o r o f o r m o r 76 a s s y r u p s form t h e t r i c y c l i c e s t e r s ( 3 5 ) .

HoQ*Me OAC

O Ac (26)

OAc

(27)

OAC

(29)X=O,Y=S ,Z=O

(28)

(30)X=S, Y = 2 = O

(31) X = Y = Z = O

(32) X = Y " 0 , Z=CH2

(35) R = Me,Ph

(34)

1,2-14igrations o f n i t r a t e groups under a c i d h y d r o l y s i s c o n d i t i o n s

i n m e t h y l 4,6-O-ethylidene-+D-glucopyranoside

n i t r a t e s has been

dem~nstrated.~ A ~d i n e t i c s t u d y of t h e n i t r a t i o n o f 1 , 4 : 3 , 6 - d i a n hydro-D-sorbitol 'mixed a c i d '

has allowed o p t i m i z a t i o n of t h e exact p r o p o r t i o n s o f 78 12% s u l p h u r i c a c i d ) t o s u g a r .

-

( 8 8 %n i t r i c a c i d

S u l p h a t i o n o f t h e a p p r o p r i a t e b l o c k e d monohydroxy d i s a c c h a r i d e s f o l l o w e d by d e p r o t e c t i o n h a s e n a b l e d t h e s y n t h e s e s o f t h e sodium s a l t s of t h e 4-sulphates prepared pyridine.

k6

( 3 6 ) . 7 9 The s u l p h a t e ( 3 7 ) h a s been

t r e a t m e n t of t h e p a r e n t g l y c o s i d e w i t h s u l p h u r t r i o x i d e S u l p h a t i o n of r u t i n h a s l e d t o t h e d e c a - a n d nona-2-

s u l p h a t e s ( 3 8 ) a n d ( 3 9 1 , b o t h o f which were shown t o be i n h i b i t o r s o f t h e complement p a r t o f t h e immune s y s t e m .

~HzOH

0

HO \

o(

otent

"2"

HO

(36)

8?

or p- L i n k e d

W

OH

xou;d

OH

ox ox (37)

(38) X

-

ox R = S03Na

(39) X = S O g N o , R = H

A c o m p r e h e n s i v e r e v i e w o f t h e c h e m i c a l a n d enzymic s y n t h e s e s o f x e n o b i o t i c c o n j u g a t e s has a p p e a r e d .

Emphasis i s g i v e n t o t h e

p r e p a r a t i o n o f s u g a r s u l p h a t e a n d m e r c a p t u r i c a c i d pathway c o n j u g a t e s

72

Carbohydrate Chemistry

of S - c o n t a i n i n g amino a c i d , s .

82

fieferences

I -

1 2

3 4

5 b

7 b

9

10 11

12 13 14

15 lU

17 16

lY 2U

N.Kunesch, C . M i e t , a n d J . P o i s s o n , T e t r a h e d r o n L e t t . , 1 9 ~ 3 7 ,2, 35b9. A.Nudelman, J . H e r z i g , H . E . G o t t l i e b , E . K e i n a n , a n d J . S t e r l i n g , C a r b o h y d r . &, 1987, 145. ir. h l o o s t e r m a n , E . W.J .Mosmuller , H .E.Shoemaker , a n d li.M.hei jer , retrahedron L e t t . , 1987, 2989. 2 , 3977. ivi.Therisod a n d A.M.Klibanov, J. Am. Ghem. S O C . , 1 9 6 7 , 1 C.Plonneret, li.l;agnet, a n d J . - C . F l o r e n t , J . C a r b o h y d r . Chem., 1 9 8 7 , 2, 221. J.%emeic, S . K u c a r , and U . A n d e r l e , C o l l e c t . Czech. Chem. Commun., 1 4 8 7 , 5 2 , 2347. S.Ahrnad a n d J . I q b a 1 , J. Chen. S o c . , Lle~;. Cornmun., 1%7, 1 1 4 . J . P . K a i n e r l i n g , K . S c h a u e r , A.K.Shukla, S . S t o l 1 , H.Van H a l b e e k , a n d J.F.G. Vliegenthart, J. Biochem., 1 9 8 7 , E, bc)l(Chem. A b s t r . , 1 9 8 7 , -lUb, 120 173). H.Ogura, K . F u r u h a t a , S . S a t o , K.Anazawa, N . I t o h , a n d Y . S h i t o r i , C a r b o h y d r . Kes., 1 9 8 7 , 1 6 7 , 77. G . J . P . C h i t t e n d e n a n d H . K e g e l i n g , Kecl. T r a v . Chim. Pays-Bas, 1 9 8 7 , 110, 44 (Chem. A b s t r . , 1 9 8 7 , 1 2 7 , 1 7 6 3 2 1 ) . H . I t o , Novuchi Kenicyusho Jiho, 1480, 13 (Chem. A b s t r . , 1 9 8 7 , 1 0 7 , 1 7 b 329). S.Tonic, J.Tomasic, L . S e s a r t i c , and b.Ladesic, Carbohydr. 1987, 141, l 5 d . U . P l u s q u e l l e c a n d K . b a c z k o , T e t r a h e d r o n L e t t . , 1 5 8 7 , 3 , 3809. B.A.aurice, G.Goldsby, a n d J . B . ~ u d d , P h y t o c h e m i s t r y , 1 9 8 7 , 20, 2567. q.Wang, f . P e i , J . S h e n , a n d K . L i , Y i y a o b o n g y e , 1 9 8 7 , lb,7 A b s t r . , 1987, 1 0 7 , 134 58U). d . i l i s c h , i . H e r i ~ i a n n , V.Wray, a n d L . G r o t j a h n , P h y t o c h e m i s t r y , 19147, &, 539. 'I'.Yoshida, 'I'.Saito, a n d S.Kadoya, Chern. Phariii B u l l . , 1 9 6 7 , 3 2 , 9 7 . 1 . b . J e n k i n s a n d M.B.boren, Chem. P n y s . L i p i d s , 1 9 8 6 , G , 225 ( c h s . A b s t r . , 1 9 6 7 , g 7 , 1% 7 9 5 j . h.l(unz, B . h u l l e r , a n d i).Schanzenbach, Angew. Chem. I n t . Ed. E n g l . , lYd7, @, 207. 'T.I(.H.Shing a n d P . i l o y d - N i l l i a m s , L. Chein. S o c . , Chem. C o m u n . , 1 4 6 7 ,

EL,

2,

w.

w,

(m.

423.

21 L2

23

24

25 2b

27 28

29

3u

J . S v o b o d a , I(.Capek, a n d J . P a l e c e k , C o l l e c t . Czech. Chem. Conunun., lYd7, 52, 70b. U.Loganathan a n d G . T r i v e d i , C a r b o h y d r . ;ies., 1 5 8 7 , I s , 117. J . H a n s e n - M o l l e r , L . l ) a l g a a r d , a n d S.H.Hansen, J. C h r o m a t o g r . , 1 9 8 7 , 99. i~.Cartnen C r u z a d o a n d iq.llartin-Loinas, C a r b o h y d r . i i e s . , 1Y67, E U , 249. X.Wu a n d F.Kong, C a r b o h y d r . &, 1987, 1 6 6 7 P . J u t t e n , J . l ) o r n h a g e n , a n d H.-D.Scharf, T e t r a h e d r o n , 1 9 8 7 , g ,4133. T.Okuda, T . H a t a n o , T.Kaneda, ivi.Yoshizaki, a n d T . S h i n g u , P h y t o c h e m i s t r y , 1 9 6 7 , 2 2 , 2053. K.liiyamoto, N . K i s h i , g . K o s h i u r a , T - Y o s h i d a , T . i i a t a n o , a n d T.Okuda, Pharm. B u l l . , 1 9 8 7 , g ,8 1 4 . 'T.Yoshida, T . H a t a n o , Pi.iqatsuda, 'I'.i)kuda, a n d T . S h i n g u , Tennen Yuki K a g o b u t s u T o r o n k a i Koen Y o s h i s h u , 1985, 7 1 8 (Chem. A b s t r . , 1987, lB, 4 4 4 4 ) . G . N u l f f , H . P a t t , a n d J . W i c i i e l h a u s , m.J. Chim., l Y 6 0 , 10, 143 (Chem. A b s t r . , 1 4 6 7 , g, 196 6 4 ~ ) .

m,

E,

w.

73

7: Esters b . P l u s q u e l l e c a n d M.Lefeuvre, T e t r a h e d r o n L e t t . , 1987, 28, 41b5. C . K o l a r , U.Knodler, F . K . S e i l e r , H.-W.Eehlhaber, V.Sinnwel1, M. S c h u l t z , and H.Paulsen, L i e b i P s Chem., 1 9 8 7 , 577. A.A.Pavia, S t r u c t . F u n c t . , P r o c . &. P e p t . Symp., Y t h , 1 9 8 5 , 4bY (Chem. A b s t r . , 1 9 8 7 , 1M, 1 9 O U l ) . d . K o c c h i , L . B i o n d i , F . E i l i r a , a n d l\,i.Gobbo, P e p t . Chem., 1985, 7 (Chem. A b s t r . , 1 9 8 7 , l U b , 214 3 4 0 ) . A.E.ZemlyaKov, V.O.Kur-yanov, V.Ya, C h i r v a , a n d A.Ya.Khorlin, B i o o r g . Khirii., l W b , j.2, 924 (Chem. A b s t r . , 1 4 8 7 , 126, 214 361). N.Noda, I'l.Ono, K . h i y a h a r a , T.l(awasaki, a n d M.Okabe, T e t r a h e d r o n , 1 9 b 7 , g ,38d9. 'I'.Shiba a n d S. l(usumoto, r a n p a k u s h i t s u Kakusan Koso, lYdi,, j l , 333 (M.H b s t r . , 19a.7, l l , 6 7 5 7 4 ) . 1~1.his0, S.'l'analta, i V l . F u j i t a , Y . Y u j i s h i m a , Y.Ogawa, a n d A.tiasegawa, C a r L o h y d r . &, 1 4 d 7 , E Z , 247. Y.ugawa, Y . P u j i s h i m a , I . l ( o n i s h i , ~I.Li.so, a n d A.hasegawa, J. C a r b o h y d r . Chem., l % 7 , 0 , 3 Y Y . 1'1. h i s o , S .Tanalta, i'i.k'u j i t a , Y . P u j i s h i m a , Y .c)gawa, H. I s h i d a , a n d A.hasegawa, C a r b o h y d r . &, 1 9 6 7 , EL,1 2 7 . ivi.Kiso, Y.Ugawa, l . l ? ' u j i s h i m a , I d i . P u j i t a , S.'TanaKa, a n d A.Hasegawa, J. C a r b o n y d r . Chem., l 9 b 7 , i, b25. I . P l a c h e r , C a r b o h y d r . &, 1 9 8 7 , I . , 7Y. l ( . l l t e d a , 'I.'l'akahashi, C.Shiniizu, S . i \ l a ~ a i n o t o , a n d K.Actiiwa, Piiarm. h u l l . , 1 9 5 7 , 2 5 , l3tij. S.Nakamoto, T . T a k a i i a s h i , K . I k e d a , a n d K.Achiwa, i h e m . Pharin. h l l . , 1 9 8 7 , 2 ,4 5 2 7 . K.IKeaa, S.NaKamoto, ' l ' . l ' a k a h a s n i , a n d li.iichiwa, Chem. Pharin. d u l l . , 1 9 0 7 , j'5, 4436. K . l k e d a , ' r . T a K a h a s h i , h.Kondo, a n d K.Achiwa, Chem. Pharm. B u l l . , 1 9 8 7 , g , 1311. Y . P u j i s h i m a , K.Kigawo, Y.Ogawa, i.I.Kiso, A.dasegawa, H . I s h i d a , arid l.Azuina, C a r b o n y d r . 1987, 1 6 7 , 317. n . S . U t ~ i n a , L.L.L)anilov, a n d V.N.Shibaev, B i o o r g . Khim., 1980, 12, 1372 (Chem. A b s t r . , 1Y67, g 7 , 198 7 7 1 ) . C . E . N i f a n t ' e v , lvl. P. X o r o t e e v , k .PI. P u k a s h o v a , A . A . ~ o r i S e n K 0 , a n d ii k:. K o c i i e t m v , I z v . Alcad. NauK SS'SR, h h i m . , 1 4 5 0 , l r 1 7 (&em. A b s t r . , 1Y67, x 7 , 115 b 5 5 j . L.L. U a n i l o v , S . b . i % l ' t s e v , a n d V . l i . S h i b a e v , Bioork. Kiiim. , l % b , g , Y 3 t (hem. i i b s t r . , 1 4 0 7 , 1 2 , 1Yb b h ) . ~ ' . J a b a , ri.i)noe, '1 .buiniyaiua, ri.Tsuhako, I\j.Yoza, a n d S . O h a s h i , c;helrl. L e t t . , 19s7, 1389. F . a r i e n b e r g e r a n d A . S t r a u b , T e t r a l i e d r o n L e t t . , l Y d l , G ,l b 4 1 . ~ . l i i c n a l s l t a , P h o s p h o r u s S u l f u r , 1486, g ,133 (Ciiern. A b s t r . ,

&.

a.

w,

.

&.

lgd'?, 106,

L14

2b7).

C a r b o n y d r . &, 1467, 107, L Y ~ . I . x . L i t v i n o v , L . l . G u r a r i i , Yu.T.StruChKov, A.B.Arbuzov, aiid I L . ' ~ . iwKriienev, I z v . nttad. iu'ault SSSK, %. k h i m . , 1980, 1274 (*. A b s t r . , 190/, K, 1 7 b 77Y). ~ \ . I \ . ~ r o r a ,J . i . r i a c l e o d , a n d J . r ' . d i l l i a i i i s , L a b e l l e d Loalga. Kadiovharm., 14tj7, x 7 , 1 3 U 4 b o ) . K . i . . l a i n , 5 . .AbLas, ~ a n d ?; . L . i \ i a t t a , L a r b o h y d r lYb7, 310. i ) . P . S r i v a s t a v a , U.tiiridsgau1, C a r b o n y d r . 1987, 324. i'i.von l t z s t e i n a n a l . U . J e n k i n s , J. CheIn. S o c . , P e r k i n T r a n s . 1, 1 ~ 6 7 ,2057. i.I.r'ranznowiaK a n d J .?'hiein, L i e b i g s Ann. Liiem. , 1987, 1 ~ 0 ~ . V . ~ . S h i b a e v , i ) . l ) z h o r u p b e ~ o v a , G . I . d l i s e e v a , a n d IJ.K.Kochetkov, b i o o r g . Khim., 1 9 d b , g,1 2 2 5 (Chem. A b s t r . , 1 9 8 7 , 1 0 7 , 1% 7 6 1 ) . O . P . S r i v a s t z v a a n d 0.11indsgau1, C a r b o h y d r . &, 1 4 6 7 , 161, l Y 5 . K.J .Auchus, S . L . K a i s e r , arid P . c . i ~ a j e r u s , P r o c . Natl. Acad. USA, 1 4 6 7 , 04,1Lbo (Chem. A b s t r . , 1 9 8 7 , 106, 214 2 4 4 ) . 11. a r a d e ,

11.1~1011, S .K. L a r i a t i , aiia I).Cnaron,

. L

J.

. w, u, m, E,

x.

74 64 05 bo 07

7u 71 72

73

74

75 7b 77

76 74 dl,

dl

QL

Curbohydra te Chemistry

w,

Y.Kondo, C a r b o h y d r . 1Y87, 162, 159. E.Lee, J . O ' C a l l a g h a n , a n d N.tiavin, C a r b o h y d r . Kes., 1987, lB, 125. J.l*Iasnovi, U . J . K o h o l i c , K . J . b e r k i , a n d K.IJ.Binkley, J. Am. M. h, 1967, 1 2 4 , 2651. N.T.Naidoo a n d li.l-'arolis, 2. Afr. J. Lhein., 1987, 4&, 57 A b s t r . , 1Ya7, 127, 115 d o u ) . C.-K.Lee, CarbohydL. ks., 1987, 1 2 ,~ 5 5 . P.i)uhainel, J . J . b d d i n c , a n d J . - Y . V a l n o t , T e t r a h e d r o n L e t t . , 19b7, 2 2 , 38Ul. 8 . E . i ~ i a r y a n o t f , S . U . N o r t e y , J. E . G a r d o c k i , k . P.Shank, a n d S .P.Uodgson, J . Pied. Chem., 19d7, &I, dBO. 'I'.Ukada, J. Lhroiiiatogr., 1967, 423, 27. C.Erkelens, H.A.H.Uilliet, L.de G a l a n , a n d E.iJ.E.de L e e r , J. ChrornatoPr., 1987, 4g4, b7. i'l.Van U u i n , J . A . P e t e r s , k.P.G.Kieboom, a n d H.Van Uekkum, C a r b o h y d r . I(es., 1937, 1 2 2 , 65. L , k a n e r a i t s u , T.'Tsuda, PI. E.Haque, K . T s u b o n o , a n d ' l . K i k u c h i , Yharm. h u l l . , lY67, 25, 3874. J . J . P a t r o n i and k.V.Stick, J. Chem., l Y 8 7 , $0, 795. S.A.Nepogod'ev arid L . V . U a k i n o v s k i i , H i o o r g . Khim., 1486, g ,711 A b s t r . , 1987, KJ-o, l U 2 b18). s . I . ~ ' i r g a n g , A.S.Snashkov, A . I . U s o v , cl.N.Marchenko, a n d V.F.Sopin, -b i o o 3 . Chim., 19157, &, 4UU (ChCk. A b s t r . , 1987, 1-0_7, 237 1 5 2 ) . E . b r o m a d z i n s k a , S . K r a u z e , a n d J . O j r z a n o w s k i , Acta P o l . Pharni., 1Y&, ft, 410 (Chern. A b s t r . , 1Y87, 1 0 6 , 214 2 4 6 ) . J . J a c q u i n e t a n d P . S i n a y , C a r b o h y d r . &, 1Y67, l L Y , 229. n . S c i l i l d t i n e c n t a n d K.I*lilde, C a r b o h y d r . 1Y87, 164, 23. V.idair, J . P . J o s e p h , J . F . P o l e t t o , a n d S . B e r n s t e i n , J. C a r b o h y d r . Lhern., lYb7, 0 , o3Y. A.Yerginan, A.C.b. Yyinp. Yer., 1960, 229, 124 A b s t r . , 1Yd7, I%, 2 3 4 6 ) .

(m.

=.

&.

(w.

w,

(u.

Halogeno-sugars An e x t e n s i v e r e v i e w on t h e p r e p a r a t i o n o f b i o l o g i c a l l y a c t i v e o r g a n o f l u o r i n e compounds h a s i n c l u d e d a u s e f u l r e v i e w o f c a r b o h y d r a t e examples.' A r e v i e w o f t h e s y n t h e s i s o f a number o f b i o l o g i c a l l y i n t e r e s t i n g a m i n o - s u g a r s r e f e r s t o some o n e - p o t r e g i o 2 s e l e c t i v e s y n t h e s e s of chlorodeoxy- and fluorodeoxy s u g a r s .

1

Fluoro-sugars

The C - 2 - f l u o r o - o l e a n d r o s y l f l u o r i d e s (1) - ( 3 ) h a v e b e e n s y n t h e s i z e d from t h e L-rhamnoside (4) by t r e a t m e n t o f t h e a p p r o p r i a t e a l c o h o l s w i t h DAST. The f o r m a t i o n o f ( 2 ) a n d ( 3 ) was p r e c e e d e d by a n

BzouBn 4 J J or

__+

or

(

Me0

F

OH

1

(4)

(1

F (3)

(2)

epimerization at C-2.

R e a c t i o n o f 2,3,4-tri-g-benzyl-D-glucose ( 5 ) , whereas i n t h e p r e s e n c e 4 o f t r i e t h y l a m i n e t h e d l f l u o r i d e (6) was t h e p r e d o m i n a n t p r o d u c t . Treatment o f t h e f l u o r o g l y c a l ( 7 ) with t r i f l u o r o a c e t y l f l u o r i d e

w i t h DAST g a v e m o s t l y t h e 3 , 6 - a n h y d r i d e

&J

BnO

OF(rJ BzO

BnO

O0n

(5)

0Bn

(6)

C

f

3

(7)

F~

820

~ C ~F 3 C~ O ~ F~

(%)

g a v e t h e 2 , 2 - d i f l u o r o g l y c o s y l f l u o r i d e ( 8 ) as t h e m a j o r p r o d u c t which s u g g e s t s t h a t 2 , 2 - d i f l u o r o d a u n o s a m i n e s h o u l d b e a v a i l a b l e by t t h i s r o u t e . 5 I o d o f l u o r i n a t i o n o f g l y c a l s u s i n g I ( c o l l i d i n e ) BF 46 h a s g i v e n r i s e t o c o r r e s p o n d i n g 2-deoxy-2-iodoglycosyl fluorides. T r e a t m e n t o f some d i - a n d t r i s a c c h a r i d e d i o l s ( 9 ) w i t h DAST g a v e Epoxide corresponding 6-monodeoxy-monofluoro p r o d u c t s ( 10).

*

t r i f l a t e s h a v e b e e n r e a c t e d w i t h t e t r a b u t y l ammonium f l u o r i d e t o g i v e p r o d u c t s of f l u o r i d e displacement of t h e t r i f l a t e i n h i g h yield,

Carbohydrate Chemistry

76

A = Protected. mono-

d.L-saccharLdes

and

' Yu o~ (11) X , = H, .Y, = OTf

(9) X = O H

e.g.,

(11)

+

0

(20)X = F

NHAc

(12) X = F, Y - H

Displacement of t h e mesylate i n t h e g a l a c t o s -

(12).

amine d e r i v a t i v e ( 1 3 ) h a s b e e n e f f e c t e d w i t h c a e s i u m f l u o r i d e a n d t h e p r o d u c t d e p r o t e c t e d t o g i v e N-acetyl-2-amino-2,6-dideoxy-6-

(14).

fluoro-D-galactose

A l t e r n a t i v e l y treatment of t h e d e r i v a t i v e

( 1 5 ) w i t h DAST g a v e t h e 6 - f l u o r i d e a n d h e n c e ( 1 4 ) .9

DAST was a l s o

used t o p r e p a r e a l l y 1 2-acetamido-2,4-dideoxy-4-fluoro-a-D-galactop y r a n o s i d e from t h e c o r r e s p o n d i n g g l u c o d e r i v a t i v e . l o Methyl 2 , 3 , 4 -

born b0.

CHZOSL5

CH20H

+Q

OBn

H

0

i

O

H

AcoQo*c

NHAc

NHAc

F

NHAc

(16)

(1 5)

(1 4)

(1 3)

CH20H

(17)

tri-~-benzyl-6-~-p-toluenesulphonyl-~-D-glucopyranosidewas c o n v e r t e d i n t o i t s 6 - d e o x y - 6 - f l u o r o d e r i v a t i v e by r e a c t i o n w i t h p o t a s s i u m f l u o r i d e i n p o l y e t h y l e n e g l y c o l .I1 The 2,3-dideoxy-3f l u o r o p e n t o s i d e (17) h a s b e e n s y n t h e s i z e d by d i s p l a c e m e n t o f t h e t r i f l a t e e s t e r o f a l c o h o l (16) w i t h t e t r a b u t y l ammonium f l u o r i d e .

12

F u r t h e r e x a m p l e s o f t h e u s e o f E t N.3HF for t h e p r e p a r a t i o n o f

3

deoxyfluoro sugars have been d e s c r i b e d .

The t r i m e s y l a t e (18) g a v e

t h e r e a r r a n g e d fluoro-amino sugar (19) by way o f an a z i r i d i n i u m i n t e r m e d i a t e , e p o x y t r i f l a t e ( 2 0 ) gave t h e product ( 2 1 ) o f d i sp l a c e m e n t o f t h e s u l p h o n a t e e s t e r o n l y , a n d 1,2:5,6-di-O--isopropylidene-3-Q-

trifluoromethanesulphonyl-a-D-allofuranose y i e l d e d t h e c o r r e s p o n d i n g CHZOMS

@

OMe

MsO

N ALL, (18)

CHZOMS

0

--+ MsO

OM^

NAll,

(1 9)

f0QM. 0

(20)

+

FQMe

0 (2')

3-deoxy-3-fluoro-glucofuranose d e r i v a t i v e . l 3 O t h e r d e o x y f l u o r o s u g a r d e r i v a t i v e s h a v e b e e n p r e p a r e d by r e a c t i o n o f t r i s ( d i m e t h y 1 a m i n o ) s u l p h o n i u m difluorotrimethylsilicate on t r i f l a t e e s t e r s w i t h i n v e r s i o n o f c o n f i g u r a t i o n . I4 D i s p l a c e m e n t o f amino-sugar s u l p h o n a t e e s t e r ( 2 2 ) w i t h KHF2 g a v e t h e r e a r r a n g e d f l u o r o - a m i n o

77

8: Halogeno-sugars s u g a r ( 2 3 ) when t h e r e a c t i o n was c o n d u c t e d i n DMF, b u t t h e

unrearranged product ( 2 4 ) with r e t a i n e d configuration i n ethylene glycol

-

t h e same a z i r i d i n i u m i n t e r m e d i a t e . 15

presumably

E p o x i d e ( 2 5 ) , d e r i v e d from L - f u c o s e , ethylene glycol t o give t h e 2-fluoro t o t h e talo-isomer

was o p e n e d w i t h K H F 2 i n

s u g a r ( 2 6 ) w h i c h was c o n v e r t e d

( 2 7 ) a n d c o u p l e d w i t h daunomycinone t o g i v e a n

a n t h r a c y c l i n e a n a l o g u e showing a n t i - t u m o u r

a c t i v i t y . l6

The r e a c t i o n

o f a c e t y l h y p o f l u o r i t e w i t h a number o f g l y c a l s h a s b e e n i n v e s t i g a t ed.

Furanoid g l y c a l s underwent s t e r e o s p e c i f i c r e a c t i o n s t o g i v e t h e

2-deoxy-2-fluoro-glycosyl

acetate.

A benzyloxy group a t

C-3

e n c o u r a g e d a d d i t i o n from t h e o p p o s i t e s i d e o f t h e d o u b l e b o n d , whereas t h e u n s u b s t i t u t e d hydroxy group induced a d d i t i o n from t h e

same s i d e .

M i x t u r e s were o b t a i n e d w i t h p e n t o p y r a n o s e g l y c a l s . 17

P h o t o b r o m i n a t i o n o f tetra-0-acetyl-6-D-glucopyranosyl f l u o r i d e g a v e ( 2 8 ) . I 8 The 2-deoxy-2-fluoro-glucoside ( 2 9 )

mostly t h e 1,l-dihalide

i s a powerful i n h i b i t o r of B-glucosidases. It was p o s t u l a t e d t h a t t h e g l y c o s i d e ( 2 9 ) g l y c o s y l a t e s t h e enzyme t o g i v e a g l y c o s i d e w h i c h i s o n l y v e r y s l o w l y h y d r o l y s e d , due t o t h e e l e c t r o n w i t h d r a w i n g f l u o r i n e s u b s t i t u e n t . 1 9 The s y n t h e s i s a n d n . m . r . s p e c t r a o f m e t h y l @Qm2

rF Jf

AcO

CIO OAc

2-deoxy-2-fluoro-a fluoro-a-

(2 8 )

NO2

F

and 6-D-glucopyranosides

a n d B-D-glucopyranosides

(29)

and m e t h y l 3-deoxy-3-

have been r e p o r t e d . 2 o

The

e n z y m a t i c i n t e r c o n v e r s i o n o f 2-deoxy-2-fluoro-D-glucose o r i t s 6 - p h o s p h a t e w i t h 2-deoxy-2-fluoro-D-mannose or i t s 6 - p h o s p h a t e 21 been o b s e r v e d i n v i v o and i n v i t r o .

has

An a u t o s y n t h e s i z e r f o r t h e p r o d u c t i o n o f 2-deoxy-2-fluoro-18-Dg l u c o s e h a s been d e s c r i b e d . 2 2

The r e a c t i o n o f l a b e l l e d a c e t y l

Carbohydrate Chemistry

78 hypofluorite with tri-0-acetyl-D-alucal D-galacta12’

, 2 3 y 2 4 and w i t h t r i - 2 - a c e t y l -

t o give, a f t e r acid hydrolysis, t h e corresponding

l a b e l l e d 2-deoxy-2-fluoro-hexoses

has

been r e p o r t e d .

The

contarninat i o n of 2-deo~y-2-~*F-D-mannose i n t h e c o r r e sp o n d i n g D-glucose d e r i v a t i v e p r e p a r e d from t h e r e a c t i o n o f l a b e l l e d a c e t y l hypofluorite with tri-2-acetyl-D-glucal h a s b e e n i n v e s t i g a t e d . 26 The n u c l e o p h i l i c d i s p l a c e m e n t o f s u l p h o n y l o x y g r o u p s w i t h l a b e l l e d f l u o r i d e i o n s h a s b e e n u s e d t o s y n t h e s i z e l a b e l l e d 2-deoxy-2-fluoroD - g l u c o s e , 2 7 28 3-deoxy-3-f f luoro-D-rnannose

2

luoro-D-glucose

. 31

Chloro-,

Bromo-,

,2 9

30 a n d 2-deoxy-2-

and Iodo-sugars

The p h o t o b r o m i n a t i o n o f tetra-9-acetyl-B-D-glucopyranosyl

chloride

g i v e s m a i n l y t h e a-bromo p r o d u c t ( 3 0 ) , w i t h t h e b r o m i n e a x i a l . 18 The s u c r o s e e p o x i d e d e r i v a t i v e s ( 3 1 ) a n d ( 3 2 ) w i t h c h l o r i d e o r b r o m i d e i o n s gave c o r r e s p o n d i n g C - 4

’

h a l o s u g a r s , 32

An i n t e n s e l y

s w e e t tetra-chloro-tetra-deoxy s u c r o s e d e r i v a t i v e ( 3 3 ) was o b t a i n e d a l o n g w i t h i t s r e g i o i s o m e r ( 3 4 ) from t h e r e a c t i o n o f 6 - g - a c e t y l sucrose with sulphuryl chloride a f t e r conventional i s o l a t i o n p r o c e d u r e s . 33

Nucleophilic opening of t h e a-nitroepoxide

( 3 5 ) gave

CH2OH

J-(= OH

t h e a-halogeno

ketones (36)

i n i t i a l l y formed p r o d u c t .

via

a n e p i m e r i z a t i o n a t C-2

of t h e

Corresponding r e a c t i o n of t h e phenyl

a n a l o g u e ( 3 7 ) was always a c c o m p a n i e d by e l i m i n a t i o n t o g i v e t h e e n o n e s ( 3 8 ) . 34

(36) X = Br,C l , I

(30)

79

8: Halogeno-sugars

Addition of iodine azide to the D-glucal derivatives (39) gave mostly 2-deoxy-2-iodo-glycosyl azides (40) derived from t,rans-diaxial addition to the double bond. D-galactal and D-xylal derivatives

(39)

R = Ac, Bn, MOM

reacted similarly although the D-xylal reaction was less stereo5 Chlorination of 4,6-g-benzylidene derivatives of selective. ' D-glucal gave predominantly the 2-chloro-2-deoxy mannosyl chloride, whereas previous work with acetyl or benzyl protected derivatives gave mostly compounds with D-gluco stereochemistry . 36 Treatment of cyclic thiocarbonates with methyl iodide has received further attention (see V01.20, p.89). In the presence of propylene oxide, some thiocarbonates gave the corresponding carbonates, whereas the furanose (41) with a primary site especially prone to nucleophilic attack afforded (42).37 The identity of the product of addition of

(4'1

(42)

(43)

OBz

hypobromous acid (NBS, H20, HOAc) to alkene (43) has been revised and now shown to be (44).38 Reaction of organoboron derivative (45) with dibromomethyl lithium gave (46) with high stereoselectivity. Displacement of the bromine with lithium benzyloxide gave (47) on which the sequence could be repeated to build up a carbohydrate of defined stereochemistry such as L-ribose derivative (48).39

"id-

(45)

The synthesis of methyl (2,3,4-tri-~-acetyl-a-D-glucopyranosyl bromide) uronate from tri-~-acetyl-1,6-anhydro-B-D-glucopyranose by standard methods has been de~cribed.~' The conversion of benzyl glycosides into glycosyl bromides by photobromination has been achieved. The initial product (49) of photobromination rearranges

Carbohydrate Chemistry

80

quickly in the presence of HMPA to the glycosyl bromide.41 Use of a 3-bromo-3-deoxy-ketosyl bromide in glycoside synthesis is mentioned in chapter 3. The conversion of methyl glycosides into glycosyl chlorides using boron trichloride has been studied and benzyl ethers, acetyl groups and other glycosyl linkages are listed as compatable with the reagent.42 A study on the formation of 6-deoxy-6-iodohexopyranosides has been done in order to find methods for the selective iodination of certain primary hydroxy groups in polysaccharides. 43 Some 6-g-tosyl glycosyl azides have been treated with LiX (X=Cl,Br,I) 44 in HMPA to give the corresponding 6-deoxy-6-halo-glycosyl azides. The 2-2-triflates (50) and (51) undergo displacement with inversion with C1-, Br- or I- in good yield.45 The successive chain extension of D-xylopyranosyl derived bromides via free radicals

generated at C-1 and C-5 is mentioned in chapter 3. A non-hydrolytic glycoside cleavage method involving an NBS-initiated oxidative addition of the ring oxygen to a remote olefinic centre is covered in chapter 3.

References 1 2 3 4 5 6 7 8 9

10 11 12 13 14 15 16 17

J.T.Welch, Tetrahedron, 1987, 43, 3123. A.Malik, N.Afza, and W.Voelter, Stud. Org. Chem. (Amsterdam), 1986, 26, 283 (Chem. Abstr. , 1987, 106,196 682) C.Bliard, F.C.Escribano, G.Lukacs, A.Olesker, and P.Sarda, J. Chem. SOC. , Chem. Commun., 1987, 368. P.Kov&, H.J.C.Yeh, and G.L.Jung, J. Carbohydr. Chem., 1987, 6, 423. A-Dessinges, F.C.Escribano, G.Lukacs, A.Olesker, and T.T.Thang, J. Org. Chem., 1987, 52, 1633. R.P.Evans and J.H.Schauble, Synthesis, 1987, 551. R.L.Thomas, S.A.Abbas, and K.L.Matta, Carbohydr. Res., 1987, 165,C14. F-Latif,A.Malik, and W.Voelter, Liebigs Ann. Chem., 1987, 617. Carbohydr. Res., 1987, M.Sharma, G.G.Potti, O.D.Simmons, and W.Korytnyk, 162, 41. T.C.Wong, R.R.Townsend, and Y.C.Lee, Carbohydr. Res., 1987, 170,27. D.Badone, G.Jommi, R.Pagliarin, and P.Tavecchia, Synthesis, 1987, 920. G.W.J.Fleet and J.C.Son, Tetrahedron Lett., 1987, 28, 3615. D-Picq and D-Anker, Carbohydr. Res., 1987, 166, 309. B.Doboszewski, G.W.Hay, and W.A.Szarek, Can. J. Chem., 1987, 65, 412. S.Kageyama, T.Onoda, T.Tsuchida, S.Umezawa, and H.Umezawa, Carbohydr. Res., 1987, 169, 241. K.Ok, Y-Takagi,T.Tsuchiya, S.Umezawa, and H.Umezawa, Carbohydr. Res., 1987, 169,69. K.Dax, B.I.Glanzer, G.Schulz, and H.Vyple1, Carbohydr. Res., 1987, 162, 13.

.

8: Halogeno-sugars 18 19 20

21 22

23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45

81

J.P.Praly and G.Descotes, Tetrahedron Lett., 1987, 28, 1405. S.G.Withers, I.P.Street, P.Bird, and D.H.Dolphin, J. Am. Chem. SOC., 1987, 109, 7531. P.Kov&CH.J.C.Yeh, and C.P.J.Glaudemans, Carbohydr. Res. , 1987, 169, 23. Y.Kanazawa, Y.Momozono, H.Yamane, T.Haradahira, M.Maeda, and M.Kojima, Chem. Pharm. Bull., 1987, 35, 895. D.L.Alexoff, J.A.G.Russel1, C.Y.Shive, A.P.Wolf, J.S.Fowler, and R.R.MacGregor, Appl. Radiat. Isot., 1986, 37, 1045 (Chem. Abstr., 1987, 106, 84 964). M.Diksic and D-Jolly, Appl. Radiat. Isot., 1986, 37, 1159 (Chem. Abstr., 1987, 106,156 781). F.Oberdorfer, W.E.Hul1, B.C.Traving, and W.Maier-Borst, Appl. Radiat. Isot., 1986, 37, 695 (Chem. Abstr. , 1987, 106,33 393) . M.Tada, T.Matsuzawa, K.Yamaguchi, Y.Abe, H.Fukuda, M.Itoh, H.Sugiyama, T.Ido, and T.Takahashi, Carbohydr. Res., 1987, 161,314. K.Ishiwata, T.Ido, H.Nakanishi, and R.Iwata, Appl. Radiat. Isot., 1987, 38, 463 (Chem. Abstr. , 1987, 107,134 568). O.T.Dejesus, J.A.Martin, N.J.Yasillo, S.J.Gatley, and M.D.Cooper, Appl. Radiat. Isot. , 1986, 21, 397 (Chem. Abstrl , 1987, 106,27 344) . K-Hamacher,H.H.Coenen, and G-Stocklin,J. Nucl. Med., 1986, 27, 235 (Chem. Abstr., 1987, 106,18 946). E.J.Knust, H.J.Machulla, and W.Roden, Radioakt. Isot. Klin. Forsch., 1986, 17,45 (Chem. Abstr., 1987, 106,214 212). M.Vogt, R.Weinreich, E.J.KnUst, and H.J.Machulla, Appl. Radiat. Isot., 1986, 37, 873 (Chem. Abstr., 1987, 106, 18 953). A.Luxen, N.Satyamurthy, G.T.Bida, and J.R.Barrio, Appl. Radiat. Isot., 1986, 37,409 (Chem. Abstr. , 1987, 106,176 751). R.Khan, M.R.Jenner, H.Lindseth, K.S.Mufti, and G.Pate1, Carbohydr. Res., 1987, 162, 199. C.K.Lee, Carbohydr. Res., 1987, 162, 53. T-Nakagawa,T.Sakakibara, S.Kumazawa, Y.Hoshijima, and R.Sudoh, Carbohydr. Res., 1987, 163,227. D.Lafont and G.Descotes, Carbohydr. Res., 1987, 166, 195. T.Sakakibara, T.Yatabe, K.Yoshino, and Y.Ishido, Chem. Lett. , 1987, 7. 795. J.J.Patroni and R.V.Stick, Aust. J. Chem., 1987, 9, S.Danishefsky, M.P.DeNinno, and G.Schulte, J. Org. Chem., 1987, 52, 3171. D.S.Matteson and M.L.Peterson, J. Org. Chem., 1987, 52, 5116. L.E.Golubovskaya and K.K.Pivnitskii, Bioorg. Khim., 1986, 12, 1379 (Chem. Abstr. , 1987, 107, 176 380). H.Hashimoto, M.Kawa, Y .Saito, T.Date, S.Horito, and J.Yoshimura, Tetrahedron Lett.. 1987. - 28.. 3505. G.R.Perdomo and J.J.KrepiEky, Tetrahedron Lett. , 1987, 28, 5595. G.O.Aspinal1, R.C.Carpenter, and L.Khondo, Carbohydr. Res., 1987, 165, 281 Z.Gyorgydeak and L.Szilagyi, Liebigs Ann. Chem., 1987, 235. R.W.Binkley, M.G.Ambrose, and D.G.Hehemann, J. Carbohydr. Chem., 1987, 2, 203.

Amino-sugars

1

Natural Products

Galactostatin (5-amino-5-deoxy-D-galactopyranose) , the galactoisomer of nojirimycin, has been isolated as a Streptomyces lydicus fermentation product and shown to be a B-galactosidase inhibitor.1 4,8-Anhydro-~-acetyl-neuraminic acid (1) has been isolated from edible birds' nest and shown to exist in 2 tautomeric forms in 2 solution. CH20H

2

Synthesis

Reviews on the syntheses of a number of biologically interesting amino-sugars , and on the synthesis and chemistry of monosaccharide isothiocyanates, have appeared. Syntheses covered in this section have been grouped according to the method used f o r introducing the amine functionality. The aminonitrile synthesis, in which a free sugar reacts with a primary amine and hydrogen cyanide, has been used to extend the chain o f D-galactose, D-glucose, and D-allose into isomeric 2-amino2-deoxy-heptoses, and thence by reaction with aryl isothiocyanates The into (glycoheptofurano)imidazolidine-2-thione derivatives. y 6 Maillard browning reaction between glucose and aspartame yielded r\l-(1-deoxy-D-fructos-1-yl) derivatives of aspartame, phenylalanine methyl ester, aspartic acid, and phenylalanine that were identified by FAB-m.s. 7 The 2-amino-2-deoxy-altrose derivative (2) was the sole product, isolated in 71% yield, from diaxial ring opening of the allo-epoxide (3) with ethanolamine, whereas in the synthesis of chiral crown ethers the bulkier P+nucleophile gave a mixture of 2- and 3-aminoThe products (4) and ( 5 1 , in 31 and 27% yield, respectively.8

83

9: A mino-sugars combination of N,bJ-dimethyl- or diethyl-trimethylsilylamine with

aluminium trichloride as catalyst has been promoted for the synthesis

(4) R -

R2

(5) R

3

R2

Scheme 1

of N,y-dialkylamino-sugars by trans-diaxial ring opening of epoxides. The reaction apparently gives an aminosilane salt which hydrolyses on work-up. Yields were in the 41-53% range, the remainder being mainly unreacted epoxide, although only the use of equimolar amounts of epoxide and reagent were reported.’ The four diastereomeric 4-amino-2,4,6-trideoxy-L-hexopyranosides (6) have been synthesized from the epimeric diols (7) and (8) by conventional epoxide formation and opening, and sulphonate displacement (by azide or acetate) reactions, and used f o r glycosylation of daunomycinone to produce the new anthracyclinone (9) and its C-4 epimer.” Both epimeric sucrose epoxides (10) were opened by attack of azide ion at C-4’,

the products being converted into 4’-amino-sucrose analogues.

11

Displacement of a sulphonyloxy group with a nitrogen nucleophile has been employed in several amino-sugar syntheses. 3-Azido-furanoside (ll), which can be converted to L-daunosamine by standard reduction and hydrolysis procedures, was obtained in 10 steps from the D-glucuronolactone derivative (12) as detailed in Scheme 2 . 12 1,6-Anhydro-2-azido- and - 2 - p h t h a l i m i d o - 2 - d e o x y - a - D - g a l a c t o p y r a n o s e s required f o r disaccharide construction (see Chapter 31, were

Carbohydrate Chemistry

84

synthesized from 1,6-anhydro-3,4-~-isopropylidene-B-D-galactopyranose in five steps: oxidation, reduction, triflation, displacement with azide or phthalimide ion, and deacetonati~n.'~ Fleet and Smith have published full details on their syntheses of 2,5-dideoxy2,5-imino-D-mannitol (Vol.19, p.169) and the piperidine precursor 2,6-imino-mannofuranoside (13) from diacetoneglucose 2 via the common intermediate azide (14) (Scheme 3). While azide (14) was obtained in 75% yield from triflate (15), the B-anomer of (15) did not undergo clean displacement.I4 A 3-azido-3 ,6-dideoxy-D-glucoside derivative has been obtained from the corresponding 3-g-triflyl-Dalloside, and used in the synthesis of amphotericin B y which has a 3-amino-3,6-dideoxy-B-D-mannopyranoside unit. l5 Eight y- (D-galactopyranos-6-y1)amino acids were obtained by reaction of standard amino acid esters with 1,2:3,4-di-~-isopropylidene-6-~-triflyl-a-I)16 galactopyranose. In the synthesis of g-linked dipeptide derivatives, e.g. (161, of 8-amino-2,6-anhydro-3,8-dideoxy-D-glycero-D-talo-octonic acid methyl ester (17), which are novel antibacterial agents which interfere with lipopolysaccharide biosynthesis, the 8-amino function was selectively introduced into the tetraol (18) using the Ph P-CBr4-LiN3 reagent system.1 7

3 CH (SEt)2

Qo:

_ L -1v _j

o+-

LOBn

@ v , v L O , M ue

- bO Me

VU-LX

O0n

(12)

Reagents L , S O ~ C L ~,'u,0u3SnH -P~ ,u, M e O H - + i + , w , B n B r -. A g z O ; v , E t S H - H C L ; vw, Raney NL, VUL, MSCL-Py , LY, NaN3-DMF Scheme 2

Scheme 3 (16) X = tj-(Arg-N~a) (17) X=NH;,

(18) X = O H

9: Amino-sugars

85

In the synthesis of 3-acetamido-3,6-dideoxy-ly2-~-isopropylidene-a-D-xylo-hexofuranos-5-ulose (see Chapter 151, introduction of the 3-amino-function involved a double inversion process (OMS I -+ N 1. l8 Amino-sugars have also be obtained from bromo3 deoxylactones. Thus 2-bromide ( 1 9 ) derived from L-rhamnonolactone yielded 2-amino-2,6-dideoxy-L-mannose (201, while 2,6-dibromide (21) with either the D-gluco- or the D-manno- configuration could be similarly converted into either the 2-amino-2,6-dideoxy- or 2,6-diarnino-2,6-dideoxy-D-mannoses (22). 19 -+

CHz Br

I

CH2X

OH (22) X = H or r;H3tL

4-Amino-4-deoxy-ketopyranosides and their 4-:-methyl analogues have been obtained by condensation o f the periodate cleavage products o f D-fructopyranose derivatives with nitromethane or nitroethane respectively, and hydrogenation of the resulting g-nitro derivatives (see Chapter 10, section 3). 20 A new method for the preparation of 2-amino-2-deoxy-glycosides involved the cycloaddition o f dibenzyl azodicarboxylate to glycals. Furanoid and pyranoid glycals, (23) and (24),gave single cycloadducts (25) and (26) which methanolysed with inversion at C-1 to 21 provide glycosides (27) and (281, respectively (Schemes 5 and 6). CHZOH

CH209

kJ++

2N/N

(

RO

R-SiMe,Bat

\

OH

C028n

(25)

(23) Reag&S

L,

,'

Bn0,C

(27)

N=N COeBn-h1,(350nm);

H2-hn'?fNr

iL, M~OH-H+;'IU,BU,NF,

Scheme 5

@,

-4

RO

boMe

O3O@*

HO QMe

R= (R-&s

(24)

Scheme 6

SiMe2But

us &. Scheme 5 )

86

Carbohydrate Chemistry

Azidonitration has been used to convert 6-deoxy-L-fucal into 2-acetamido-2,6-dideoxy-L-galactose (y-acetyl-L-fucosamine) ,21a and (6S)-6-2 H1-D-glucal triacetate (prepared from labelled D-glucose, c.f., V01.20, p.59) into (6S)-(6-2H1)-2-acetamido-2-deoxy-D-glucose, the latter being used in a study of the rotamer population about the C-5/C-6 bond.22 The methyl glycoside (29) of the antibiotic component 3-amino-2,3,6-trideoxy-3-~-methyl-L-xylo-hexose, its C - 3 epimer L-vancosamine, and its C-4 epimer (an amino-precursor of the nitro-sugar L-decilanitrose), were obtained from the 4-uloside (30) by a-alkylation to yield a separable mixture of C - 3 epimers (31) followed by selective reduction of the ketone, L-selectride or sodium borohydride providing products with an axial o r equatorial hydroxy-group, respectively (Scheme 7 ) . The starting ketone (30) was prepared by oxidation of a known alcohol ( c . f . , Vo1.17, p . 9 3 ) .

Using similar methodology, D-rubranitrose (32) was synthesized from methyl 4,~-~-benzylidene-2-deoxy-a-D-ribo-hexopyranosid-3-ulose oxime. 23 Addition of ammonia to an unsaturated sulphone yielded, 24 after acetylation, the 3-acetamido-derivative ( 3 3 ) .

Further investigations have been reported on the synthesis and the 0- and N-glycosidation of anomalously linked nucleosides of structure (34) formed by condensation of adenine derivatives or phthalimide with 2-deoxy-D-ribose presumably & y an enal Benzyl and methyl intermediate ( c . f . , V01.20, p.95) .25-28 acosaminide ( 3 5 ) has been obtained in 35% overall yield from L-rhamnal diacetate (36) by conjugate addition of hydrazoic acid to the masked enal (37) and mild glycosidation, followed by chromatographic separation from a 4 component mixture of the major a-Larabino-isomer (Scheme 8). 29

87

9: Amino-sugars

An e f f e c t i v e s y n t h e s i s o f E-(1-deoxy-D-fructos-1-y1)amino a c i d s , e L , t h e p r o d u c t ( 3 8 ) t h a t would b e p r o d u c e d i n t h e M a i l l a r d r e a c t i o n of L-valine w i t h D-glucose, i n v o l v e d r e d u c t i v e a m i n a t i o n w i t h t h e D - f r u c t o s e d e r i v e d a l d e h y d e ( 3 9 ) (Scheme 9 ) . 30 Methyl

(-Jk 90

GH

+

CHO

HO

CHz NUCH(PrL) COZH

OH

(391 ( 39) Reagents. i, L-VaLinc - NoBHJCN , LL,Resvr(H+) - H a 0

Scheme 9

0-(2-acecamido-3,4,6-tri-~-acetyl-2-deoxy-~-D-gluco- and mannop y r a n o s y 1 ) - L - s e r i n a t e s h a v e b e e n o b t a i n e d by r e d u c t i o n (H2-Pd/C) o f t h e s u g a r oxime p r e c u r s o r s . R e a c t i o n o f t h e s e 2-oxime d e r i v a t i v e s w i t h sodium a z i d e s e r v e d t o r e p l a c e t h e i r 3-acetoxy-group t o g e n e r a t e a n e p i m e r i c m i x t u r e o f 3-azides . 31 A z a c y c l i c 2-deoxy-KDO a n a l o g u e s (40) h a v e b e e n s y n t h e s i z e d i n a 2:l B : a - r a t i o from KDO (3-deoxy-D-manno-octulosonic a c i d , 411, t h e n i t r o g e n f u n c t i o n b e i n g i n t r o d u c e d b y r e d u c t i v e a m i n a t i o n (Scheme lo), b u t t h e y p r o v e d t o b e CH2OH

r

OH o

bOH H 3

+uN: ” $i20 0;r .

COZH

v-VLL.~

(401

(4’) Reagulks: L , Me2--

H + ; i i , N a B H 3 C N - N H + O k - M e O H ; k i , B n O C O U ; w , C H 2 N ~ ;v, (CacL),- D M S O - C ~ J N ;

v i , NaBHq ; vii, M s U - € t 3 N ; vtii, P&-

0;ix,

PrkNEt

;x ,

H+

Scheme 10

p o o r i n h i b i t o r s o f CMP-KDO s y n t h e t a s e C c . f . , compounds ( 1 6 ) a n d ( 1 7 ) i n t h i s c h a p t e r w h i c h were p o t e n t i n h i b i t o r s ] . A noteworthyfeature of t h i s s y n t h e s i s was t h e h i g h s t e r e o s e l e c t i v i t y ( > 9 5 % i n v e r s i o n a t

C-6) o f t h e o x i d a t i o n - r e d u c t i o n s e q u e n c e ( s t e p s v a n d v i ) . 3 2 d e t a i l s on t h e s y n t h e s i s o f L - s i b i r o s a m i n i d e

from L-rhamnose

Full

88

Carbohydrate Chemistry

(c.f., Vo1.19, p.90) have been published, and a synthesis of the related 3-acyl-kanosamine included. 33 A 6-C (2-pyridyl)aminol-6deoxy-substituted gluco-pentasaccharide has been synthesized as an a-amylase substrate by reductive amination of an 6-aldehydo-sugar .34 The synthesis of amino-sugars from chiral non-carbohydrate starting materials continues to be a popular area of work. Three groups have employed 13-lactam intermediates. Condensation of the D-glyceraldehyde Schiff base adduct (42) with methoxyacetyl chloride gave B-lactam ( 4 3 ) which isomerized in acid to the lactone (44) which yielded the 3-amino-pentose (45) on reduction (Scheme 11). 35 The synthesis of 2,3-dideoxy-2-amino-3-C-hydroxymethyl-a-D-mannofuranoside and related 3-C-branched amino sugars via a 6-lactam is covered in Chapter 14. The fused 13-lactam (46) was a common intermediate in the synthesis of L-acosamine precursor (47) and L-daunosamine derivative (48) from ethyl (S)-3-hydroxybutanoate (49) (Scheme 1 2 ) , both conversions employing an oxidative decarboxylation step (reagent viii). 36

Ethyl (S)-lactate has been the primary source of chirality in three amino-sugar syntheses. 2-Amino-2-deoxy-L-lyxonate (50) was almost the exclusive diastereomer formed when magnesium bromide was employed as the Lewis acid catalyst for the aldol conaensation of L-lactaldehvde derivative (51) with silyl ketene acetal ( 5 2 )

89

9: Amino-sugars

(Scheme 1 3 ) a l t h o u g h i t was o n l y i s o l a t e d i n 4 0 % y i e l d ( c . f . , l o w e r s e l e c t i v i t y a t t a i n e d w i t h s i m i l a r r e a c t i o n s e a r l i e r ; G.Guanti

et

a l . , T e t r a h e d r o n L e t t . , 1 9 8 5 , 3 5 1 7 ) . E s t e r ( 5 0 ) was c o n v e r t e d t o l a c t o n e ( 5 3 1 , a known i n t e r m e d i a t e for t h e s y n t h e s i s o f L-daunosamine a n d L-vancosamine (~01.18,p . 9 4 ) .37 The *-3,4-dihydroxy-

oo

C 0, E3ht CHo

0

4

Bn2N +

Me

~

NBnz

'

OH Hlii.os & BnO

(52)

(5') ~

OSLMe3

4

.. u.

-'"+

Me

HO

Me

~ i, M~&-,-cH~cL~, ~ ~ d -4OOC s :; ii,, H z - P d / C

NHC020n

(53)

(50)

; ' L B, n 0 2 C C L - N d C 0 3

iv, C F ~ C O I H

Scheme 13

hex-2-enoate

( 5 4 1 , d e r i v e d from a n L - l a c t a l d e h y d e d e r i v a t i v e i n 4

s t e p s including t h e non-chelation

c o n t r o l l e d a d d i t i o n of m e t h y l

p r o p i o l a t e a n i o n ( c . f . , V01.20, p . 9 7 ) , underwent i n t r a m o l e c u l a r M i c h a e l a d d i t i o n of t h e c a r b a m a t e g r o u p , t h e p r o d u c t ( 5 5 ) b e i n g c o n v e r t e d t o N-acetyl-L-acosamine

( 5 6 ) (Scheme 1 4 ) .

s y n t h e s i s of t h e 3-epimeric N-benzoyl-L-ristosamine reported.38

A related was a l s o

The (25 , 3 S ) - n i t r i l e ( 5 7 ) , a v a i l a b l e from e t h y l (S)-

S c h e m e 14

l a c t a t e or d i m e t h y l L - t a r t r a t e , h a s b e e n e l a b o r a t e d t o g-benzoyl-Ldaunosamine ( 5 8 ) i n 4 1 % o v e r a l l y i e l d , t h e a d d l t i o n a l two c a r b o n atoms b e i n g a d d e d

via

t h e magnesium e n o l a t e ( 5 9 ) (Scheme 15).

The

( 2 R , 3 S ) - i s o m e r of n i t r i l e ( 5 7 ) was s i m i l a r l y e l a b o r a t e d t o E-benzoyl -L-acosamine [ t h e C - 4 e p i m e r o f ( 5 8 1 1 i n 25% o v e r a l l y i e l d . 3 9 A n o t h e r s y n t h e s i s o f F-benzoyl-L-daunosamine

( 5 8 ) employed t h e

Carbohydrate Chemistry

90

a d d i t i o n - rearrangement ( w i t h s i l y l group t r a n s f e r ) o f k e t e n e s i l y l a c e t a l ( 6 0 ) w i t h t h e c h i r a l n i t r o n e ( 6 1 ) d e r i v e d i n 8 s t e p s from d i e t h y l L - t a r t r a t e , t h e adduct ( 6 2 ) being obtained s t e r e o s p e c i f i c 40 a l l y (Scheme 16). Ph

\."

Me

-4

u-v

N o j i r i m y c i n ( 6 3 ) and 1-deoxvnojirimycin have been s y n t h e s i z e d from d i e t h y l L - t a r t r a t e via t e t r i t o l (64). W i t t i g c h a i n e x t e n s i o n g a v e C6-alkene ( 6 5 ) , which was f u n c t i o n a l i z e d by S h a r p l e s s e p o x i d 41 a t i o n (Scheme 1 7 ) .

( S ) - C a r v o n e (66) s e r v e d as a n o v e l s o u r c e o f c h i r a l i t y i n a l e n g t h y f o r m a l s y n t h e s i s o f g-acetyl-L-acosamine (67) the c y c l o p e n t a n o n e d e r i v a t i v e ( 6 8 ) a n d i n v o l v i n g a Beclanann r e a r r a n g e m e n t 42 and two E a e y e r - V i l l i g e r o x i d a t i o n s (Scheme 1 8 ) .

I n t h e p r e p a r a t i o n of racemic g-benzoyl-ristosamine ( 6 9 ) from ( 7 0 1 , t h e i n i t i a l e p o x i d a t i o n was o n l y m o d e r a t e l y s t e r e o s e l e c t i v e , p r o v i d i n g t h e d e s i r e d t h r e o - e p o x i d e (71) a l o n g w i t h i t s e r y t h r o - i s o m e r and d i e p o x i d e i n 4 2 , 1 2 , and 10% y i e l d s

t h e amino-diene

9: Amino-sugars

DL-

91

Me

(70)

Re9en.h.

L,

MCPDA

Me

DL-(71)

, U , ResLn(C03*-)-McOH

;uc, H30+

, LV, BzCL- N a H M 3 , v, 0 3

D L- (69) ;VL, Me,S

S c h e m e 19

respectively (Scheme 19). 4 3 An y-sulphinyl Diels-Alder approach has been employed in the synthesis of racemic precursors for the aminohexose moieties of the Streptomyces product staurosporine and nogalorol, as exemplified for the amino-hexulose (72) (Scheme 20) .44'45

The epimeric mixture of racemic 3-amino-2,3-dideoxy-pentonolactones (73, R=H) and their 3-C-methyl analogues (73, R=Me) have been obtained from azetidinones ( 7 4 ) , R=H or Me respectively, which are readily available by cycloaddition of the appropriate diene with chlorosulphonyl isocyanate (Scheme 21). 46 F o r a further synthesis of a racemic amino-sugar, see Scheme 27.

NH6z (74) R = M , M e

(73) R = H , M e

Reaqenits: L , Me0ti-H'; L, B z c 1 - P ~; L, 0 6 0 4 - M e j N O

S c h e m e 21

3 Reactions Kinetic studies have been reported on the hydrolysis of the Schiff bases formed from 2-amino-2-deoxy-D-glucose and substituted benzaldehydes ,47 and the geometric isomerization of the S c h i f f bases

92

Carbohydrate Chemistry

formed between 2-amino-2-deoxy-D-glucose, -galactose and -mannose and 4-hydroxybenzaldehyde. 48 The reaction of l-deoxy-l-propylaminoD-lyxo-hexulose with phenyl isothiocyanate in methanol gave a complex mixture of compounds from which the heterocyclic derivatives (75) and (76) were isolated.49 PN :

'

S

0

9;;

(77) R' = H , Rz= OH

H O I NOH HO p h CH20H

(78) R'=Ac, R 2 = m - B r

Pr

(75)

(76)

The ~-(2,2-diacylvinyl)-protected derivative (77) was readily obtained from 2-amino-2-deoxy-D-glucose, and yielded mixtures of the corresponding pyranosides and furanosides on Fischer glycosidation. N-Deprotection could be effected under mild conditions (Resin-OH- in H20-Me2CO). 50 The related bromide (78) , a reasonably stable crystalline solid, has been used as a donor in Koenigs-Knorr glycasidation reactions to give 1,2-trans-glycosides in good yields, which could be N-deprotected with chlorine in chloroform or by basic hydrolysis. 51 1,2- trans-Glycosides were also available using 2-Nallyloxycarbonyl derivatives of 2-amino-2-deoxy-D-glucosyl bromides or acetates, the !-protecting group being easily removed with palladium (0) complexes.52 Results from the synthesis and binding to isolated rat hepatocytes of a variety of E-acylated 2-amino-2deoxy-6-D-glucopyranosides and mono- and di-2-methyl ethers of allyl 2-acetamido-2-deoxy-B-D-galactopyranoside and allyl 2-acetamido-2,4dideoxy-2-fluoro-a-D-galactopyranoside suggested that the 2-, 3- and 4- but not 6-hydroxy-group was involved in the binding.53 A four stage synthesis of p-nitrophenyl 2-acetamido-2-deoxy-f3-D-glucopyranoside from 2-amino-2-deoxy-D-glucose hydrochloride has been reported. " Syntheses of 0- and g-glycosides of other amino-sugars are covered in Chapter 3. Methyl 2-amino-2,4-dideoxy-B-D- and L-threo-pentopyranosides have been resolved by chromatographic separation of diastereomeric esters, and their absolute configurations determined.55 Derivatives of 6-amino-6-deoxy-D-galactose have been prepared as shown in Scheme 22, and by another route.56 Benzylidenation of 1-deoxy-1-p-toluidino-D-fructose (PhCHO in EtOH) followed by acetylation yield the 2,3-acetal (79) 57

.

93

9: Amino-sugars

iV, E t j N - PhMe

S c h e m e 22

The synthesis and biological activity of MDP(N--acetyl-muramoylL-alanyl-D-isoglutamine) and bacterial lipid A analogues continue to attract considerable attention. Aminolysis of lactones ( 8 0 ) has been used to prepare muramoylamides (81) (Scheme 23).58 The

&A" 0

NHAc

MeCH CO-L- A h - O M e

Me H (80) R = Ac,Tr, Bn,

(0')

,a- D-GILNAG(A& Reag&s:

i,

C1- A h - O M e

- lmidarole -

(C~H,~>+A~BZ

S c h e m e 23

disaccharide analogue (82), with a modified 3-substituent containing an a-aminobutanoyl moiety (L-Abu) replacing the L-alanyl moiety, has been synthesized by standard means. It was 3-4 times more active as an immunoadjuvant than MDP itself and less pyr~genic.~' The synthesis of a 2-benzamido-5,6-epithio-D-glucofuranoside analogue of MDP is covered in Chapter 11, while conformational studies on two MDP derivatives are reported in Chapter 21. Lipid A, its relatives lipid X and Y, and their analogues are esterified 2-amino-2-deoxy-D-glucopyranose derivatives, as exemplified by the recently synthesized Proteus mirabilis lipid A ( 8 3 ) . 6o Novel synthetic aspects generally involve protecting group manipulations and carboxylic and phosphoric ester forming procedures; further details may be found in Chapter 7. The majority of publications have come from the groups of Achiwa (mostly full 60-64 disclosures of preliminary communications, see Vols 19 and 20)

94

Carbohydrate Chemistry

and Hasegawa,65-69 who employed the related amines (84) and (851, respectively, as key intermediates that could be variously acylated at N-2 then 0-3, and then phosphorylated at 0-4. Further elaborat, r conversion to ion involved glycosylation at 0-6 (as with K I I O ~ ~ ) o

(84) R = Ally1 (65)

R=Bn

1-c-

1-thio- o r 1-2-phosphono-analogues .68 The synthesis of a phosphonate analogue of lipid X is covered in Chapter 17. Phenacylthiourea derivatives, e.g., (86), have been prepared from 2-amino-2-deoxy-D-glucose and cyclized to y-thiazolyl derivatives, e . g. , ( 8 7 ) .7 0 Similarly the 2-amino-2-deoxy-D-glyceroa-L-gluco-heptopyranose derivative (88) has been converted (with CSCl,) to isothiocyanate (89) and thence to various thiourea derivatives, e g. , (90).71 The reaction of 2-alkylamino-2-deoxy-D-

.

glucose with isothiocyanates is covered in Chapter 10. Two new reagents f o r reducing azides to amines have been applied is the fastest to some carbohydrate examples: [Et3NH][Sn(SPh)31 reductant for azides yet reported, while Bu2SnH2 is compatible with water and carbonyl functionality.7 2 The 'H- and I3C-n . m . r. spectra of methyl 2-acetamido-2-deoxy-Dgalacto- and D-gluco-pyranosides in the presence of lanthanide ions suggested preferential complexat ion with the E-acetyl group, the result having relevance to understanding the binding of calcium (11) ions to polysaccharides containing acetamido-sugar units. 73

4 Di- and Tri-amino-sugars Methyl 2,4-diacetamldo-2,4,6-trideoxy-a-D-ido-, -a-D-talo-, -a-Da l t r o - , and -a-D-manno-pyranosides have been synthesized from methyl

9: A mino-sugars

95

2-~-acetyl-3,4-anhydro-6-deoxy-a-D-galactopyranosi~e by standard procedures, particularly azide opening of epoxides and mesylate displacement reactions. 74 Methyl a-D-kijaqoside (91) has been synthesized from nitro-alcohol (92) (c.f., V01.20, p.lll), the conversion involving a triflate displacement with azide and selective reduction (NaBH4-NiC12) of the azido-function in the presence of a nitro-group.75 A 15 step synthesis of benzyl 2,4diacetamido-2,4,6-trideoxy-D-galactopyranoside ( 9 3 ) , a model for a fragment of Streptococcus pneumoniae "complex polysaccharide", from 1,6-anhydro-B-D-mannopyranose, involved sequential displacements with inversion of triflyloxy groups from C-2 anc? C - 4 by azide ion.76

'b

A ' H N b O b

OMe

y

CH20H

CH2NH2

NO2

(92) x = H , Y = O H (91) X = NHCOZMe, Y = H

G 2 > 0 H

HO NHAc

(93)

(94)

@OH

'7

NHAG

H e C H C O - L- A h

(95)

t

The synthesis of 2,6-diamino-2,6-dideoxy-D-mannose (22, X=NH C1) 3 has been covered in section 2. Six 2,3-diamino-MDP (muramoyl dipeptide) analogues varying in the peptide moiety, e.g., (95), have been synthesized for a study of adjuvant activity, starting from a previously reported 2,3-diaminosugar (c.f. , V01.20, p . 103, ref .65). 77 The 4-hydroxypurpurosamine B derivative (96) and its C-6 epimer the known have been synthesized from 2-amino-2-deoxy-D-glucose 3-deoxy-derivative (97) (Scheme 24). Nitromethane addition to 6-aldehyde (98) gave the L-talo-nitro-sugar ( 9 9 ) as the only isomer in high yield. The nitrogen function was then relayed from C-7 to C-6 via formation and catalytic hydrogenation of a 6,7-epimine. 78 Other syntheses of diamino-sugars have employed non-carbohydrate starting materials. 6-epi-D-Purpurosamine D (loo), a constituent of the antibiotic fortimycin A , has been elaborated from the adduct (101) obtained by coupling the L-alanine derived aldehyde (102) with the L-malic acid derived Wittig salt (103) (Scheme 25); the aminomesylate displacement with inversion group at C-2 was introduced by azide. 79 High pressure Lewis acid-catalyzed [4+2]cycloaddition of a-aminoaldehyde (104) or (105; from L-alanine) to diene (106) yielded hex-2-enosides (107) and (108), which were converted to the 2 ,6-diamino-sugars DL-purpurosamine C (109)8o or 6-epi-a-D-purpurosaminide (110),81 respectively (Scheme 26). Regioselective hydro-

=

-

96

Carbohydrate Chemistry

.. .

u -Lv

__z

Me R e n c j e n t s : i, I4H-TYF

; u, D n B r - N a H ; iLi, I, ; LY, B u j S n H

= - CO2Bn

S c h e m e 25

boration of alkenes (107) or (108) yielded the alcohols (111) which were aminated via the 2-oxime. The racemic 4,5-diamino-4,5-dideoxy-lyxopyranose and 5-deoxy-5amino-lyxopyranosylamine derivatives, (112) and (113), have been obtained from the regioisomeric cycloadducts of acylnitroso dienoR

(104) R = U

,, i

N H C 0, But

(1 05) R = Me

0 L1u

*OMe

-

NHCO~BLL'

-+-

tNHAc

LV-VUi

3

(106) DL-(107)

R

R =H

(1

2

"1

(108) R - M e R e a g e n t s L, E ~ ( F o d ) ~ - 2 0 k b ~ ,,'HU , UI, thexylborme-Me2S,then H,O,-NaOH LV, P C C - M o l S~wt?, V, N H Z 0 ~ , VL, A C zO- % , V U , BHg THF ,VItt, T F A

NHAc

DL.- (109) R = H (110) R = M e

Scheme 26

philes with dihydropyridine derivative (114), the addition being regioselective for adduct (115) when R=Ph, Bn or Me (Scheme 27). Attempts to induce chirality using chiral nitroso compounds were 82 not very successful.

97

9: Amino-sugars

I

ii -w

f--Reagents: i, RCONUOH - NaIO, ; L,OSO~-NMMO;.&,H,-MfC ;Lv, A c 2 0 - P ~

N\C02Me

DL-(112)

S c h e m e 27

References 1

2 3 4 5

6

7 8

9 10 11

12 13 14 15 16 17 18 19 20 21 2la 22

Y.Miyaki and M.Ebata, J. Antibiot., 1987, 40, 122. 162 , 445 V.Pozsgay, H.Jennings, and D.L.Kasper, Eur. J. Biochem., 1987, (Chem. Abstr., 1987, 107,97 032). 26, 283 A.Malik, N.Afza, and W.Voelter, Stud. Orq. Chem. (Amsterdam), 1986, (Chem. Abstr. , 1987, 106,196 682). Z.J.Witczak, Adv. Carbohydr. Chem. Biochem., 1986, 44, 91. J.A.Galbis Perez, J.L.Jimenez Requejo, J.C.Pa1acios Albarran, M .Ava10s Gonzalez, and J.Fernandez-Bolanos, An. Quim., Ser. C, 1986, 82, 11 (Chem. Abstr. , 1987, 107,7477) . R-Babiano Caballero and J.A.Galbis Perez, An. Quim., Ser. C., 1986, 82, 92 (Chem. Abstr. , 1987, 107,217 968). T.C.Huang, A.A.Soliman, R.T.Rosen, and C.-T.Ho, Food Chem., 1987, 24, 187 (Chem. Abstr., 1987, 107,132 778). G.Toth, W.Dietrich, P.Bak6, L.Feniche1, and L.TGke, Carbohydr. Res. , 1987, 168, 141. A.Malik, N.Kazmi, A.Q.Khan, and Z.Ahmad, J. Chem. SOC., Chem. Commun., 1987, 1073. A.Martin, C.Monneret, and M.Pais, Carbohydr. Res., 1987, 166,59. R.Khan, M.R.Jenner, H-Lindseth, K.S.Mufti, and G.Patel, Carbohydr. Res., 1987, 162, 199. M.K.Gurjar and S.M.Pawar, Tetrahedron Lett. , 1987, 28, 1327. M.Kloosterman, H.T.De Hey, D.De Wit, and J.H.van Boom, Recl. Trav. Chim. Pays-Bas, 1986, 105,229 (Chem. Abstr. , 1987, 107, 7443). G.W.J.Fleet and P.W.Smith, Tetrahedron, 1987, 43, 971. K.C .Nicolaou, R.A. Daines , T .K.Chakraborty, and Y .Ogawa, J. Am. Chem. SOC. , 1987, 109, 2821. A.Malik, Z.Ahmed, N.U.H.Kazmi, and A.Q.Khan, Z. Naturforsch., B : Chem. Sci., 1987, 42, 514 (Chem. Abstr., 1987, lo?, 97 085). A.Claesson, A.M.Jansson, B.G.Prinq, S.M.Hammond, and B.Ekstrom, J. Med. Chem. , 1987, 2, 2309. M.K.GurJar and V.J.Pati1, Indian J. Chem., Sect. B, 1986, 1017 (Chem. -Abstr., 1987, 107, 134 563). K.Bock, I.Lundt, and C.Pedersen, Acta Chem. Scand., Ser. B, 1987, 41, 435. F.W.Lichtenthaler, A.Pashalidis, and H.J.Lindner, Carbohydr. Res., 1987, 164, 357. B.J.Fitzsimmons, Y.Leblanc, and J.Rokach, J. Am. Chem. SOC., 1987, 109, 285. A.K.M.Anisuzzaman and D.Horton, Carbohydr. Res., 1987, 169, 258. Y-Nishida, H.Hori, H.Ohrui, and H.Meguro, Carbohydr. Res., 1987, 170, 106.

z,

Carbohydrate Chemistry

98

23 A.Klemer and H.Wilbers, Liebigs Ann. Chem., 1987, 815. 24 T.Sakakibara, I.Takai, Y-Tachimori, A.Yamamoto, Y.Ishido, and R.Sudoh, Carbohydr. Res. , 1987, 160, C3. 25 M.S.Motawia, E.S.Andreassen, E.B.Pedersen, and J.P.Jacobsen, Liebigs Ann. Chem., 1987, 787. 26 J.Andersen and E.B.Pedersen, Liebigs Ann. Chem. , 1987, 705. 27 M.S .Motawia, G.A.M.Nawwar , E .S .Andreassen, J.P. Jacobsen, and E .B.Pedersen , Liebigs Ann. Chem., 1987, 1111. 28 E.B.Pedersen, -Nucleosides Nucleotides, 1987, 6, 43. 29 J.-C.Florent and C-Monneret, J. Chem. SOC., Chem. Commun., 1987, 1171. 30 D.J.Walton, J.D.McPherson, T.Hvidt, and W.A.Szarek, Carbohydr. Res., 1987, 167, 123. 31 Z.Smiatacz and E.Paszkiewicz, Bull. Pol. Acad. sci.. Chem. , 1986, 34, 397 (Chem. Abstr., 1987, 107,218 028). 32 D.W.Norbeck and J.B.Kramer, Tetrahedron Lett. , 1987, 28, 773. 33 J.Yoshimura, A.Aqee1, K.-I.Sato, R.B.Singh, and H.Nashimoto, Carbohydr. Res., 1987, 166,253. 34 K.Omichi and T.Ikenaka, J. Chromatogr., 1987, 420, 158. 35 M.S.Manhas, J.M.Van Der Veen, D.R.Wagle, V.R.Hegde, S.S.Bari, Z.Kosarych, M.Ghosh, and L-Krishnan, Indian J. Chem., Sect. B, 1986, 1095 (Chem. Abstr., 1987, 107,97 026). 36 D.-C.Ha and D.J.Hart, Tetrahedron Lett., 1987, 28, 4489. 37 L.Banfi, S-Cardani,D.Potenza, and C.Scolastico, Tetrahedron, 1987, 43, 2317. 38 M.Hirama, T.Shigemoto, and S.Ito, J. Org. Chem., 1987, 52, 3342. 39 T.Hiyama, K.Kobayashi, and K-Nishide, Bull. Chem. SOC. Jpn., 1987, 60, 2127. 40 Y.Kita, F.Itoh, O.Tamura, Y.Yuan Ke, and Y.Tamura, Tetrahedron Lett., 1987, 28, 1431. 41 H.Iida, N.Yamazaki, and C.Kibayashi, J. Org. Chem., 1987, 52, 3337. 42 T.Kametani, Y .Suzuki, C.Ban, K.Kanada, and T.Honda, Heterocycles, 1987, 2, 1789. 43 W.R.Roush, J.A.Straub, and R.J.Brown, J. Orq. Chem., 1987, 52, 5127. 44 R.P.Joyce, J.A.Gainor, and S.M.Weinreb, J. Org. Chem., 1987, 52, 1177. 45 S.M.Weinreb, J.A.Gainor, and R.P.Joyce, Bull. Chem. SOC. Belg. , 1986, 95, 1021 (Chem. Abstr. , 1987, 106, 176 776). 46 F.M.Hauser, S.R.Ellenberger, and R.P.Rhee, J. Org. Chem., 1987, 52, 5041. 47 F.V.Pishchugin, X.Sh.Sharshenalieva, and N.S.Dakenova, Zh. Obshch. Khim., 1986, 56, 953 (Chem. Abstr. , 1987, 106,67 601). 48 F.V.Pishchugin, Z.Sh.Sharshenalieva, and N.S.Dakenova, Izv. &ad. NauJc. Kirq. SSR, 1986, 56 (Chem. Abstr., 1987, 106,5337). 49 J.Fernandez-Bolanos, M.Trujillo Perez-Lanzac, J.Fuentes Mota, and A.Cert Ventula, A n . Quim., Ser. C, 1986, 82, 260 (Chem. Abstr., 1987, 107, 154 667). 50 M.G.Garcia-Martin, C.Gasch, A.Gomez-Sanchez, M.J.Dianez, and A.L.Castro, Carbohydr. Res., 1987, 162, 181. 51 A.Gomez-Sanchez, M-Garcia-Martin,and C.Gasch, Carbohydr. Res., 1987, 2, 255. 52 P.Boullanqer, J.Banoub, and G.Descotes, Can. J. Chem., 1987, 65, 1343. 53 T.C.Wong, R.R.Townsend, and Y.C.Lee, Carbohydr. Res., 1987, 170,27. 54 H.Li, K.Zhonq, and Y.Chen, Shanghai Keji Daxue Xuebao, 1985, 60 (Chem. Abstr., 1987, 106,120 168) 55 G.Anker, J-Attaghrai, D.Picq, and D.Anker, Carbohydr. Res., 1987, 159, 159. 56 P.Gries, H.Kristen, and C.Voge1, Carbohydr. Res. , 1987, 167, 87. 57 I.F.Strel'tsova, Izv. %ad. Nauk. Kirg. SSR, 1986, 43 (Chem. AbStr., 1987, 106, 138 695). 58 D.Keqlevic, M.Ponqracic, and D.Kantoci, Croat. Chem. Acta. , 1985, 58, 569 (Chem. Abstr. , 1987, 106,176 836). 59 J.Farkas, M-Ledvina, J.Brokes, J.Jezek, J.Jajicek, and M.Zaora1, Carbohydr. Res. , 1987, 163, 63. 60 K.Ikeda, T.Takahashi, H.Kondo, and K.Achiwa, Chem. Pharm. Bull., 1987, 35, 1311. 61 K.Ikeda, T.Takahashi, C.Shimizu, S.Nakamoto, and K.Achiwa, Chem. Pharm. Bull. , 1987, 35, 1383.

z,

.

9: A mino-sugars 62 63 64 65 66

67 68

69 70

71 72 73 74 75 76 77 78 79 80 81 82

99

K.Ikeda, S.Nakamoto, T.Takahashi, and K,Achiwa, Chem. Pharm. Bull., 1987,

35, 4436. -

S.Nakamoto, T.Takahashi, K.Ikeda, and K.Achiwa, Chem. Pharm. Bull., 1987,

35, 4517. -

S.Nakamoto and K.Achiwa, Chem. Pharm. Bull., 1987, 35, 4537. M.Kiso, S.Tanaka, M-Fujita, V.Fujishima, Y.Ogawa, H.Ishida, and A.Hasegawa, Carbohydr. Res. , 1987, 162, 127. M.Kiso, S.Tanaka, M.Fujita, Y .Fujishima, Y .Ogawa, and A.Hasegawa, Carbohydr. Res., 1987, 162, 247. M.Kiso, M.Tanahashi, A.Hasegawa, and F.M.Unger, Carbohydr. Res., 1987, 163, 279. Y.Ogawa, Y.Fujishima, I.Konishi, M.Kiso, and A.Hasegawa, J. Carbohydr. Chem. , 1987, 6, 399. M-Kiso, Y.Ogawa, Y.FuJishima, M.Fujita, S.Tanaka, and A.Hasegawa, J. Carbohydr. Chem., 1987, 6, 625. J.Fuentes Mota, M.C.O.Mellet, J.M.G.Fernandez, M.A.Pradera Adrian, and I.M.G.Monterrey, Carbohydr. Res., 1987, 162, 307. J.Fuentes Mota, M.Avalos Gonzalez, J.L.Jimenez Requejo, J.C.Palacios Albarran, and 1.M.Gomez Monterrey, An. Quim., Ser. C, 1985, 81, 239 (Chem. Abstr., 1987, 106,120 166). M.Bartra, F.Urpi, and J.Vilarrasa, Tetrahedron Lett., 1987, 28, 5941. K.Isumi, Carbohydr. Res., 1987, 170, 19. K.Capek, J.Capkova, J.Jary, Y.A.Knire1, and A.S.Shashkov, Collect. Czech. Chem. Commun., 1987, 52, 2248. R.M.Giu1iano and T.W.Deisenroth, J. Carbohydr. Chem., 1987, 6, 295. J.P.G.Hermans, C.J.J.Elie, G.A.van der Marel, and J.H.van Boom, J. Carbohydr. Chem., 1987, 6, 451. A.Calvo-Mateo and F.G.De Las Heras, Liebigs Ann. Chem., 1987, 1017. K.Kanai, I.Sakamoto, S.Ogawa, and T.Suami, Bull. Chem. SOC. Jpn., 1987, 60, 1529. K.Kamiyama, Y.Urano, S.Kobayashi, and M.Ohno, Tetrahedron Lett., 1987, 28, 3123. A.Golebiowski, U.Jacobsson, M.Chmielewski, and J.Jurczak, Tetrahedron, 1987, 43, 599. A.Golebiowski, U.Jacobsson, and J.Jurczak, Tetrahedron, 1987, 43, 3063. A.Defoin, H.Fritz, C.Schmidlin, and J.Streith, Helv. Chim. Acta, 1987, 70, 554.

10 Miscellaneous Nitrogen Derivatives

1

G ly c o s y 1am ine s

A review on the synthesis of glycopeptides has covered the formation of 5-linked compounds by reaction between glycosylamines and aspartic acid units. The synthesis of 2-acetamido-2-deoxy-B-Dglycopyranosylamines and their E-acylation with amino-acid The derivatives (Vol. 20, p. 106) has been published in formation and stability of glycosylamines from drugs with a primary aromatic amine moiety (e.g., procaine, procainamide, and 4-aminobenzoic acid) and various reducing Sugars has been examined, using an h.p.1.c. assay.3 Reaction between base and free sugar has similarly been employed in the synthesis of N-glycopyranosides (D-glc, D-xyl, D-ara) of ~-amino-2-(ethoxycarbonyl)inciole ,4 and the dextrophane prototype (11, which is a novel cavity molecule (Scheme

1). The synthesis and rearrangement reactions of some diglycosylamines has been reinvestigated. Di(B-D-glucopyranosyl)amine, the main product from transglycosylation of B-D-glucopyranosylamfne, yielded a mixture of tetra-0-acetylated B,B- and a,B-isomers on

acetylation, and these could be deacetylated without further anomerization. B-D-Xylopyranosylamlne behaved analogously, except that the tri-0-acetylated B,B- and a,B-isomers yielded only The 1,2-transdi ( B-D-xylopyranosyl )amine on deacetylation. selective condensation of acylated glycosyl halides with free bases has been employed in the synthesis of the E-B-D-glucopyranosyl and seven derivative of 2,5-dimethyl-4-ethynyl-4-piperidinol, antitumor active 9-hydroxyellipticine N-glycosides, e.g., a-L8 arabinosyl derivative (2) , with improved water solubility.

1 0: Miscellaneous Nitrogen Derivatives

101

The acetylation of 5-amino-4-glycosylamino-pyrimidines, including some conditions which cause cleavage of the E-glycosidic bond, has been examined. The reaction of penta-2-benzoyl-a-D-glucopyranose with liquid ammonia in organic solvent yielded l,l-bis(benzamido)-l-deoxy-6-~-benzoyl-D-glucitol ( 3 ) (29% yield), three partially benzoylated g-benzoyl-a-D-glucofuranosylamines (24%) and four partially benzoylated derivatives of a-D-glucopyranose (10%).10 D-Galactosylamine (4) was used as the chiral template in a diastereoselective Strecker synthesis of a-aminonitriles which could be converted into D-amino-acids, e.g., (5) (Scheme 2).11 R2

R JN -kfH2

t

yNd L

0R' (4) R ' = Me3C,C0

R a g e d & : i, R2CHO; iL, Me3SiCN- &'OH- ZnCI2 or S n C 1 + - ~ ~;F%

H30'

Scheme 2

2-Deoxy-2-iodo-glycosyl phosphoramidates, e.g., (6), have been 12 synthesized from glycals, e.g., using D-glucal ( 7 ) (Scheme 3 ) .

The synthesis and chemistry of glycosyl isothiocyanates has been reviewed,13 and the phase transfer catalysed synthesis of acetylated glycosyl isothiocyanates of D-galactose and lactose from the corresponding glycosyl bromides reported.l4 The 5-9-D-gluco- and -galacto-pyranosyl 2-amino-5-carbamoyl-lY3,4-oxadiazoles (8), potential antiviral agents, were obtained from the condensation of the corresponding peracetylated glycosyl isothiocyanates with oxamic

102

Carbohydrate Chemistry

hydrazide (H2MNYCOCONH2), cyclization (Hgo) and deacetylation. 1- and 5 - ~ - ( T e t r a - ~ - a c e t y l - B - D - g l u c o p y r a n o s y l ) - 2 , ~ - i s o d i t h i o b i u r e t s (9) were obtained from either the glucosyl isothiocyanate o r the glucosyl 2-2-benzylisothiocarbamide by addition of the requisite isothiocarbamide o r isothiocyanate moiety. l6 Chlorination (C12-CHC1 ) of tetra-g-acetyl-6-D-glucopyranosyl isothiocyanate (10) 3 yielded the dichlorlde (11) which was used to synthesize a range of derivatives as shown in Scheme 4.1 7

[j,N=C==”C)

Cyclic ureas (12) and (13) have been obtained by reaction of 2-amino-2-deoxy-D-glucose and 2-amino-2-deoxy-D-glycero-L-guloheptose, respectively, with silver cyanate. The pyranosidic cyclic ureas (14) were synthesized f r o m the 2-amino-2-deoxy-Dglucosyl azides (15, R=H or Ac, R’=H) the phosphimines (16) (Scheme 5). Under the same conditions, the 2-acetamido-glucosyl

ss

0

toH (13)

CHpOH

10: Miscellaneous Nitrogen Derivatives

103

An a z i d e (15, $=R2 =Ac) g a v e t h e s y m m e t , r i c a l c a r b o d i i m i d e (17).l9 n . m . r . s t u d y o f c o n f o r m a t i o n a l l y r i g i d compounds s u c h as ( 1 8 ) u s i n g 2D methods r e v e a l e d d e v i a t i o n s from t h e e x p e c t e d K a r p l u s r e l a t i o n s h i p b e t w e e n 3Lc,H v a l u e s and d i h e d r a l a n g l e s . 2 o 2-Alkylamino-2deoxy-aldoses condense w i t h i s o t h i o c y a n a t e s t o g i v e ( g 1 y c o f u r a n o ) i m i d a z o l i d i n e - 2 - t h i o n e s s u c h as t h e D - g l u c o - d e r i v a t i v e (19) ( s e e also C h a p t e r 9 ) . I s o m e r i z a t i o n a n d d e h y d r a t i o n o f t h i s l a t t e r Acetylation of d e r i v a t i v e y i e l d e d t h e C - g l y c o s i d e ( 2 0 ) . 21 compounds s u c h a s ( 2 1 ) y i e l d e d p e r a c e t a t e s s u c h a s ( 2 2 ) r a t h e r t h a n

HO

0

9)

R= H

CHzOR

R = Ac

RO

CCL3

pyranosidic structures ascribed e a r l i e r . 22

'H-,

13C-

a n d 15N-n.m.r.

and e . i a n d f.d.m.s. s t u d i e s have b e e n r e p o r t e d on I 3 C - a n d 1 5 N l a b e l l e d 2-methylthiooxazoline d e r i v a t i v e s , e . g . , (231, r e a d i l y s y n t h e s i z e d by s e q u e n t i a l c o n d e n s a t i o n o f a l d o s e s ( 6 p e n t o s e s , 6 h e x o s e s ) w i t h t h i o c y a n a t e i o n t h e n m e t h y l a t i o n ; i n some c a s e s b o t h f u r a n o i d a n d p y r a n o i d d e r i v a t i v e s were o b t a i n e d . 2 3 Chmielewski a n d co-workers h a v e r e v i e w e d ( m o s t l y t h e i r own) work on t h e h i g h - p r e s s u r e [ 2 + 2 l c y c l o a d d i t i o n o f a c t i v e i s o c y a n a t e s t o and have r e p o r t e d t h a t t h e a d d i t i o n o f t r i c h l o r o a c e t y l glycals y24 i s o c y a n a t e t o v a r i o u s g l y c a l s y i e l d s m i x t u r e s o f [ 2 + 2 1 - a n d C4+21c y c l o a d d u c t s i n which t h e i s o c y a n a t e a d d s a n t i t o t h e C-3 substituent, o f t e n w i t h t h e l a t t e r a d d u c t p r e d o m i n a t i n g . Thus t r i s - g - ( t r i m e t h y l s i l y 1 ) - D - g l u c a l y i e l d e d t h e B-lactam ( 2 4 ) a n d t h e C 4 + 2 l c y c l o a d d u c t ( 2 5 ) ( s e e a l s o C h a p t e rs 1 3 and 1 4 ) . 2 5 T h e M a i l l a r d r e a c t i o n o f D-xylose and g l y c i n e has b e e n i n v e s t i g a t e d by I 3 C - a n d I 5 N - s o l i d s t a t e - n . m . r . a n d d i f f u s e r e f l e c t a n c e i . r . spectroscopic examination of t h e i n s o l u b l e melanoidins prepmed u s i n g I 3 C - a n d l 5 N - l a b e l l e d s u b s t r a t e s . A l t h o u g h no d e f i n i t e s t r u c t u r e c o u l d be f o r m u l a t e d for t h e s e m e l a n o i d i n s , t h e f a t e of t h e 26 l a b e l l e d c a r b o n atoms was e l u c i d a t e d t o some e x t e n t .

Carbohydrate Chemistry

104

2

Azido-sugars

A new procedure for converting arnines and amides t o the corresponding azides is exemplified in Scheme 6. It involves controlled reduction of E-alkyl-N-nitrosoamides to hydrazides, e.g., (26), followed by ni-trosation - fragmentation.27 FHzNHAc i,iL

uecu3-

i, N O + H $ o i - A

c p AcOH - NaOAc

, L , Zn

, W,

Am'ONO

Scheme 6

Azido-sugars can be synthesized by nucleophilic displacement of reactive chlorosulphate groups from chiral centres with potassium azide. Less reactive chlorosulphates underwent chlorine displacement to yield azidosulphates, but these groups could be replaced by azide with inversion using crown ethers at room temperature. 2a Syntheses of 2,3,4-tri-g-acetyl-6-azido-6-deoxy-a and B-D-gluco- and galacto-pyranosyl azides from the corresponding 6-2-tosylates employed lithium azide in HMPT.29 In the synthesis of amphotericin B, which has a 3-arnino-3-deoxy-B-D-rnannopyranoside unit, an p ( 3 azido-3,6-dideoxy-D-glucopyranosyl)trichloroacetirnidate was prepared from a 3-g-triflyl-D-alloside. 30 The 3-azido-2,3-dideoxy-Derythro-pentofuranoside (27), a potential precursor for the 3'-azido -2',3'-dideoxy-nucleoside AZT, has been synthesized from the methyl Methy 1 4-azido-4,6-dideoxy-ci-D-mannoxyloside (28) (Scheme 7). 31

pyranoside (29), synthesized from methyl 2,3-g-isop~opylidene-Drhamnopyranoside [involving sequential C - 4 epimerization by oxidation-reduction, 4-g-triflation, and azide displacement (with KN _3 18-crown-6) reactions] has been converted into the glycosyl acceptor (30) and donor (311, which were used for the synthesis of 1,2-alinked di- and tri-saccharide units found in Brucella A and M

I 0: Miscellaneous Nitrogen Derivatives

105

(29) R1=OMe, Rz= R’sH (30) R’POMS, R L H , R3=Bn (31)

R’ = C1,

R2= Ac , R3= Bn

a n t i g e n s . 32 E p o x i d e ( 3 2 1 , a n d two r e l a t e d e p o x i d e s c o n t a i n i n g n u c l e o p h i l i c a l l y d i s p l a c e a b l e g r oups, can be opened w i t h t h e a z i d e r e a g e n t shown (Scheme 8 ) , 3 3

w h e r e a s a n a r o m a t i c amine g a v e t h e 4-aminos u g a r e p o x i d e ( 3 3 ) which t h e n g a v e t h e e p i m i n e ( 3 4 ) on r e a c t i o n w i t h

t h e a z i d e r e a g e n t . 34

Two new r e a g e n t s h a v e b e e n d e v e l o p e d f o r r e d u c i n g a z i d e s t o amines , a n d a p p l i e d t o some c a r b o h y d r a t e e x a m p l e s .

9ne

([Et3NH1CSn(SPh)31) i s t h e f a s t e s t r e d u c i n g a g e n t f o r a z i d e s y e t r e p o r t e d , w h i l e t h e o t h e r (Bu2SnH2) i s c o m p a t i b l e w i t h w a t e r and carbonyl groups.

35

ReactTonsof 2 , 3 - a n h y d r o - 3 - n i t r o - p y r a n o s i d e s

w i t h a z i d e and o t h e r

n u c l e o p h i l e s a r e c o v e r e d i n C h a p t e r 15.

3

N i t r o - and N i t r o s o - s u g a r s

and Glycosyl N i t r o E s -

The n i t r o - s u g a r (35) was t h e main p r o d u c t i s o l a t e d c h r o m a t o g r a p h i c a l l y ( 1 8 % y i e l d ) from c o n d e n s a t i o n b e t w e e n n i t r o m e t h a n e a n d t h e d i a l d e h y d e ( 3 6 ) , d e r i v e d from s e l e c t i v e l e a d t e t r a a c e t a t e c l e a v a g e of s u c r o s e .

With n i t r o e t h a n e t h i s d i a l d e h y d e g a v e t h e b r a n c h e d

n i t r o - s u g a r ( 3 7 ) ( 7 . 4 % ) i n which t h e c e n t r e a s t e r i s k e d had e p i m e r i z e d p r i o r t o condensation. The t e t r a a l d e h y d e ( 3 8 ) from p e r i o d a t e c l e a v a g e of s u c r o s e c o n d e n s e d w i t h n i t r o m e t h a n e t o y i e l d t h e dinitro-sugar

( 3 9 ) ( 2 3 % ) . Both compounds ( 3 5 ) a n d ( 3 9 ) were

r e d u c e d (Raney N i ) t o t h e c o r r e s p o n d i n g arr-ino-sugars

. 36

106

Carbohydrate Chemistry

OH

(35) CH2OH

CH2OH HO

AcHN

(41) X=OH,Y= H

OH

(43)

(42) X- H , Y = O H

A d d i t i o n o f n i t r o m e t h a n e t o t h e d i a l d e h y d e g e n e r a t e d from p e r i o d a t e c l e a v a g e o f f r u c t o p y r a n o s i d e ( 4 0 ) has b e e n r e - e x a m i n e d . The two n i t r o - s u g a r s ( 4 1 ) a n d ( 4 2 ) w e r e o b t a i n e d i n a 4:l r a t i o , a n d w e r e r e a d i l y c o n v e r t e d t o t h e c o r r e s p o n d i n g 4-amino-4-deoxy-ketop y r a n o s i d e s by h y d r o g e n a t i o n . The p e r a c e t a t e o f ( 4 1 ) g a v e t h e d i a r n i n o n i t r o - s u g a r ( 4 3 ) as t h e major p r o d u c t upon t r e a t m e n t w i t h m e t h a n o l i c ammonia a n d s u b s e q u e n t E - a c e t y l a t i o n . Similar products were o b t a i n e d from 1 , 2 - ~ - i s o p r o p y l i d e n e - a - D - f r u c t o p y r a n o s e , which a l s o p r o v i d e d a route i n t o b r a n c h e d - c h a i n amino- a n d n i t r o - s u g a r s ( s e e C h a p t e r 1 4 ) . 37 Analogous p e r i o d a t e c l e a v a g e - n i t r o m e t h a n e c o n d e n s a t i o n was employed i n t h e s y n t h e s i s o f 1 , 4 , 7 - t r i o x a s p i r o C 5 . 5 1 u n d e c a n e frcm 1,2-0-ethylene-B-D-fructopyranose ( s e e C h a p t e r 24). 38 2,6-Anhydro-l-deoxy-l-nitroalditols h a v e b e e n p r e p a r e d by a p p l i c a t i o n o f known p r o c e d u r e s i n v o l v i n g a d d i t i o n of n i t r o m e t h a n e t o D - g l u c o s e , D-mannose, D - g a l a c t o s e , D - x y l o s e , D - l y x o s e , a n d L - a r a b i n o s e a n d s u b s e q u e n t c y c l i z a t i o n . Only i n t h e c a s e o f D-xylose were f u r a n o i d p r o d u c t s o b t a i n e d i n a d d i t i o n t o p y r a n o i d References t o t h e s y n t h e s i s of branched-chain n i t r o p r o d u c t s . 39 s u g a r s may a l s o b e f o u n d i n C h a p t e r s 9 a n d 1 4 , a n d t o r e a c t i o n s of a-nitro-epoxides i n Chapter 15. C a r b o h y d r a t e n i t r o n e s a n d n i t r o s o - s u g a r s h a v e b e e n employed as chiral auxiliaries. C h i r a l a - a m i n o p h o s p h o n i c a c i d s , e.g.-, ( R ) (44), h a v e b e e n o b t a i n e d i n h i g h e n a n t i o m e r i c e x c e s s by n u c l e o p h i l i c 40 a d d i t i o n t o N - g l y c o s y l n i t r o n e s , e . g . , ( 4 5 1 , as shown. i n Scheme 9 . The a p p l i c a t i o n o f d i p o l a r c y c l o a d d i t i o n t o r e l a t e d n i t r o n e s i n t h e ?he s y n t h e s i s of c h i r a l a c i v i c i n (46) i s o u t l i n e d i n Scheme 1 0 . 1-C-nitroso-D-mannofuranosyl c h l o r i d e ( 4 7 ) has a s i g n i f i c a n t l y

10: Miscellaneous Nitrogen Derivatives

107

-

higher r e a c t i v i t y towards alkenes than o t h e r a-chloronitrosocompounds.

It undergoes h i g h l y d i a s t e r e o s e l e c t i v e e n e r e a c t i o n s t o

(481, from which c h i r a l a l l y l i c (49), may b e o b t a i n e d o n h y d r o l y s i s (Scheme

yield nitrone hydrochlorides, e.g., hydroxylamines, e . g . , 42 11).

Cl'

1

OH

HONH

u

b (49)

(48)

> 80%

e.e

Scheme 11

4 N i t r i l e s , Oximes, H y d r o x y l a m i n e s , a n d I m i n e s Improved s y n t h e s e s o f t h e D-mannosyl a n d D - x y l o s y l

cyanides ( 5 0 ) and

(51), r e s p e c t i v e l y , from t h e c o r r e s p o n d i n g a , B - g l y c o s y l a c e t a t e s ( u s i n g Me SiCN-BF:OEt2 i n MeN02) have b e e n r e p o r t e d . 43 Using t h e 3 same r e a g e n t s y s t e m , 2,3,4,6-tetra-@benzyl-a,f3-D-galactoand g l u c o - p y r a n o s y l a c e t a t e s gave s e p a r a b l e ca. 1:l m i x t u r e s of g l y c o s y l 'H- a n d I 3 C - N . r n . r . s p e c t r a of a number o f p e r b e n z o y l c y a n i d e s . 44

(51) O B I

a t e d a l d o n i t r i l e s , t h e i r a z i d e a d d i t i o n p r o d u c t s [ t h e 5-(polyben-

I08

Carbohydrate Chemistry

~oyloxyalkyl)tetrazoles], and related acyclic compounds have been

.

interpret e d 45,46 The deoxyhydroxylamino-sugars (52) and ( 5 3 ) have been synthesized from buloside (54) either by an oximation - reduction sequence, or by Michael addition to the enolone (55) (Scheme 12) (c.f., Vol.11, p.112). The 4-ulosides (53) could be oximated, but reduction of these ketones or the derived oximes proved difficult. Benzoylation of the g-methyl derivative (53, $=Me) unexpectedly gave alkene (56). 47 Reduction of keto-oximes to aminodeoxyalditols is covered in Chapter 18.

CH208~

u.

(561

(53) . - R'= Me, Ph,

& Five sugms

Reagents: L , N U ~ O H ; U , N ~ . O H , C N - U C L - M ~ O U ; ~ ~ ~ , R Nj H O Y iv, B Z C L - P ~ Scheme

@.g.,R' 12

The 6-aldehydo-D-galactose derivative (57) could be employed as a chiral auxiliary in the synthesis of a set of a-alkylated (S)valine, (S)-leucine and (S)-isoleucine derivatives (58) in high enantiomeric excess, &y alkylation of imine (59) (Scheme 13). b 8

CHO

5

R'

Hydrazones, Osazones, and Related Heterocycles

Treatment of the benzoylhydrazone (60), derived from the corresponding ketone, with boiling acetic anhydride afforded the epimeric 3-Deoxyaldos-2-ulose bis ( thiosemicarbazones ) were mixture (61).49 readily obtained from D-glucose Ci.e. (6211, D-arabinose, and D-glycero-D-gulo-heptose on reaction with thiosemicarbazide (in

I 0: Miscellaneous Nitrogen Derivatives

109

p-toluidine-HOAc-H20-EtOH under reflux), presumably by Amadori-type rearrangements and eliminations.50 Heterocyclization (Ac20-py) of the 4-arylthiosemicarbazones of free sugars (Glc, Gal, Man, D-Ara, and lactose) yielded many compounds of type (63). 51.

6 Other Heterocyclic Derivatives ~-(2-Nitrovinyl)amino-2-deoxy-D-glucose (64), synthesized by reaction of the free amino-sugar with ethyl 2-nitrovinyl ether in methanol at OOC, converted to the 2-(alditol-l-yl)-4-nitropyrrole (65) on being heated in methanol. E-Alkylpyrroles were similarly produced from the E-alkylated free sugar. 1-Amino-1-d-eoxy-0fructose gave the 3-(alditol-l-yl)-analogue (66).52 3-(D-erythroTrihydroxypropyl)-l-neopentylpyrrole-2-carboxaldehyde (67) was isolated as an advanced Maillard reaction product from D-glucose and neopentylamine in phosphate buffer under physiological conditions of pH and temperature.53

HO

The nitroheterocycle ( 6 8 ) , which exists in four tautomeric forms only one of which is shown, was obtained in modest yield from addition of diazomethane to nitro-olefin (69). Analogous results were obtained with two other sugar nitro-olefins . 54 The isomeric dimers (70) re'sulted from condensation of the 3-nitro-sugar (71) with sodium azide !in DMF), the configuration at C-2 being established through alternative syntheses of specifically C - 1 and c-2 deuterated analogues.55 The bis-benzoxazine (72) was synthesized by acylation of

Carbohydrate Chemistry

110

a n t h r a n i l i c a c i d w i t h tetraacetyl-D-galactaric a c i d d i c h l o r i d e ( 7 3 ) and subsequent dehydrative c y c l i z a t i o n . (PhNH2-PC13) y i e l d e d t h e b i s - q u i n a z o l o n e R

( 7 4 ) . 56 *co{oAc

Q?

(68)R=

Further reaction

AcO


OAc

R'

(70) R=

x =AN

b

(72)R1= R', X a 0

NO2

(73) R' = COCL

(69) R = tCH=CHNOz

(74) R'= R 2 , X = NPh

F u l l d e t a i l s on t h e s y n t h e s i s o f t h e s p i r o - a n d b i c y c l o n u c l e o s i d e s r e p o r t e d l a s t y e a r (V01.20, p . 1 1 5 , Scheme 1 3 )

have

b e e n p u b l i s h e d . 57 The c y c l o a d d u c t s formed from g l y c a l s a n d d i b e n z y l a z o d i c a r b o x y l a t e , a n o m a l o u s l y l i n k e d n u c l e o s i d e s from 2-deoxy-D-ribose,

and

c e r t a i n o t h e r h e t e r o c y c l i c d e r i v a t i v e s a r e covered i n Chapter 9 .

References 1 2

3 4

5 6 7 8

9

10 11 12 13 14 15

16 17 18

H.Kunz, Angew. Chem., Int. Ed. En&, 1987, 26, 294. L.M.Likhosherstov, O.S.Novikova, V.A.Derevitskaya, and N.K.Kochetkov, Akad. Nauk SSSR, Ser. Khim., 1986, 1663 (Chem. Abstr., 1987, 107,40229). S.Okada, H.Nakahara, H.Isaka, T.Taga, and K-Miyajima,Chem. Pharm. Bull., 1987, 35, 2495. M.S.Shengeliya, M.M.Viqdorchik, K.F.Turchin, Yu.A.Ershova, V.A.Chernov, V.G.Avramenko, and N.N.Suvorov, Zh. Orq. Khim., 1986, 22, 1868 (Chem. Abstr., 1987, 107, 198 779). A.G.M.Barrett and N.S.Mani, Tetrahedron Lett., 1987, 28, 6133. K.Linek, J-Alfoldi,and J.Defaye, Carbohydr, Res., 1987, 164, 195. A.Sh.Sharifkanov and Zh.A.Tleukeeva, I z v . &ad. Nauk Kaz. SSR, Ser. Khim., 1986, 78 (Chem. Abstr., 1987, 107, 176 3 3 6 ) . T.Honda, M.Inoue, M.Kato, K.Shima, and T.Shimamoto, Chem. Pharm. Bull., 1987, 3 5 , 3975. MTRodriquez, C Rodriguez , M. Melgarejo , R Asenjo , M .Nogueras, and A.Sanchez, Nucleosides Nucleotides , 1987, 887. A.E.Salinas, J.F.Sproviero, and V.Deulofeu, Carbohydr. Res., 1987, 170,71. H.Kunz and W.Sager, Angew. Chem., Int. Ed. Engl., 1987, 26, 557. D-Lafont and G.Descotes, Carbohydr. Res., 1987, 166,195. Z.J.Witczak, Adv. Carbohydr. Chem. Biochem., 1986, 44, 91. I.Rakumatullaev, O.A.Tashpulatov, and V.A.Afanas'ev,Zh. Org. K h i m . , 1987, 23, 454 (Chem. Abstr. , 1987, 107, 176 384). M.wojtowicz, Acta Pol. Pharm., 1985, 42, 521 (Chem. Abstr., 1987, 107, 115 887). S.P.Deshmukh, B.N.Berad, and M.G.Paranjpe, J. Indian Chem. SOC., 1986, 63, 315 (Chem. Abstr. , 1987, 107,40 233) T.Hasse1 and H.P.Miiller, Angew. Chem., Int. Ed. Engl., 1987, 26, 359. J.A.Galbis Perez, F.Zamora Mata, and P.Turmo Fernandez, Carbohydr. Res., 1987, 163,132.

.

.

h,

.

10: Miscellaneous Nitrogen Derivatives 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43

44 45 46 47 48 49 50 51 52 53 54 55 56 57

111

J.Kovacs, I.Pinter, A.Messmer, G.Toth, and H.Duddeck, Carbohydr. Res., 1987, 166,101. F.H.Cano, C.Foces-Foces, J.Jim&ez-Barbero, A.Alemany I M.Bernab6 , and M.Martin-Lomas, J. Org. Chem. , 1987, 52, 3367. J-Fernandez-Bolanos,1.Robina Ramirez, F.Zamora Mata, Benarquez Fonseca, and J.Fuentes Mota., Ann. Quim., Ser. C, 1986, 82, 211 (Chem. Abstr., 1987, 107, 154 666). M.Avalos Gonzalez, J.L.Jimenez Requejo, J.C.Palacios Albarran, M.D.Ramos Montero, and J.A.Galbis Perez, Carbohydr. Res., 1987, 161,49. R.M.Davidson, G.D.Byrd, E.White, V.Sam, A-Margolis, and B.Coxon, Magn. Reson. C h m . , 1986, 24, 929 (Chem. Abstr. , 1987, 107,154 598). M.Chmielewski and J-Jurczak,J. Carbohydr. Chem., 1987, 5, 1. M.Chmielewski and Z.Kaluza, Carbohydr. Res., 1987, 167, 143. L.M.Benzing-Purdie and J.A.Ripmeester, J. Carbohydr. Chem., 1987, 6, 87. J.Garcia and J.Vilarrasa, Tetrahedron Lett., 1987, 28, 341. N.T.Naidoo and H.Parolis, S. Afr. J. Chem. , 1986, 39, 208 (Chem. Abstr., 1987, 107, 134 559) . Z.Gyorgydeak and L.Szilagyi, Liebigs Ann. Chem., 1987, 235. K.C.Nicolaou, R.A.Daines, T.K.Chakraborty, and Y.Ogawa, J. Am. Chem. SOC., 1987, 109, 2821. G.W.J.Fleet and J.C.Son, Tetrahedron Lett., 1987, 28, 3615. M-Gerken and D.R.Bundle, Tetrahedron Lett., 1987, 28, 5067. G-Janairo,W.Kowollik, and W.Voelter, Liebigs Ann. Chem., 1987, 165. F.Latif, A.Malik, and W.Voelter, Liebigs Ann. Chem., 1987, 717. M.Bartra, F.Urpi, and J.Vilarrasa, Tetrahedron Lett., 1987, 28, 5941. K.J.Hale, L.Hough, and A.C.Richardson, Tetrahedron Lett., 1987, 28, 891. F.W.Lichtenthaler, A.Pashalidis, and H.J.Lindner, Carbohydr. Res., 1987, 164, 357. K.H.Aamlid, L.Hough, A.C.Richardson, and D.Hendry, Carbohydr. Res., 1987, 164, 373. A.Fortsch, H.Kogelberg, and P.KG11, Carbohydr. Res. , 1987, 164,391. R.Huber and A.Vasella, Helv. Chim. Acta, 1987, 2, 1461. S.Mzengeza, C.M.Yang, and R.A.Whitney, J. Am. Chem. SOC., 1987, 109,276. G.Kresse, A.Vasella, H.Felber, A.Ritter, and B.Ascher1, Red. Trav. Chim. Pays-Bas, 1986, 105,295 (Chem. Abstr. , 1987, 106,66 707) . G.D.Kini, C.R.Petrie, W.J.Hennen, N.K.Dalley, B.E.Wilson, and R.K.Robins, Carbohydr. Res., 1987, 159, 81. M.-T.Garcia LGpez, F.G.De Las Heras, and A.San FGlix, J. Carbohydr. Chem., 1987, 6, 273. N.B.D'%corso and I.M.E.Thie1, Carbohydr. Res. , 1987, 167, 301. N.B.D'Accorso and I.M.E.Thie1, Carbohydr. Res., 1987, 167, 19. J.M.J.Tronchet, N.Bizzozero, and F.Barbalat-Rey, J. Carbohydr. Chem., 1987, 6. 155. U.Sch&lkopf, R.T&le, E.Egert, and M.Nieger, Liebigs Ann. Chem., 1987, 399. E.S.H.El Ashry, M.A.A.Rahman, Y.E.Kilany, and N.Rashed, Carbohydr. Res., 1987, 163,123. D.Horton, R.G.Nicko1, and O.Varela, Carbohydr. Res., 1987, 168,295. E.S.H.El Ashry, M.A.Nassr, Y.E1 Kilany, and A-Mousaad,Bull. Chem. SOC. Jpn., 1987, 60, 3405. A.Gomez-Sanchez, F.-J.Hidalgo, and J.-L.Chiara, Carbohydr. Res., 1987, 167, 55. F.G.Njoroge, A.A.Fernandes, and V.M.Monnier, J. Carbohydr. Chem., 1987, 6, 553. H.H.Baer and I.Gilron, Carbohydr. Res., 1987, 164,486. T.Sakakibara, T.Nakagawa, and M.Funabashi, Carbohydr. Res., 1987, 168,47. E.S.H.El Ashry, N.Rashed, and A.~ousaad,J. Carbohydr. Chem., 1987, 6, 599. J.P.Ferris and B.Devadas, J. Org. Chem., 1987, 52, 2355.

Thio- and Seleno-sugars

A r e v i e w on i i l o n o s a c c h a r i d e

dpiieared.

1

i s o t h i o c j a r l a t e s and t h i o c y a n a t e s has

The a n o d i c d e p r o t e c t i o r l of t h e c a r b o n j l gl’ouy h a s b e e n

Applied t o d e t h i o a c e t a l i z n t i o n

o f SUba1-S; i t wa5 i’ound t h a t 2 - i s o L

$ r . o p y l i d e n e a c e t a l s w e r e u n a f f e c t e d by t h e t r e a t m e r i t . i’eracetylated Jittld

froid

1 , L - t-r-a n s - I - t h i o g l y c o s e s h a v e b e e n

c h l o r i d e arid t h i o a c e t i c a c i d , it h

d

Q.

w i t h t h e interrflediacy

Of

t h e 1-

T h e r e a c t i o n oi D-glucose ailn D - x j l o s e

cis-cl.iloro-derivative.’ I,J

i n high

t h e p e r a c e t y l g l j c o g y r a r i o s e s b j t r e a t u e n t blith aluminium

- 13 e t h y 1- p r o p a n e - 2 - t i ?

i o 1 i n c once n t r a t e d h y d r o c h 1o r i c a c i d

d l l ’ o r d e d t n e c o r r e s p o n d i n g t e r t - b u t j l 1- t h i o - g l y c o p y r a n o s i d e s iirionleric i n i x t b r e . L)-xylose,

The a c e t y l a t e d a l d e h y d o - d e r i v a t i v e s

and D - e r y t h r o s e

/t

zave d i - t e r t - S u t j l

Oi’

as a n

D-glucose,

d i t h i o a c e t a l s w i t h 2-

l~zth~l-~,ro~arie-r-thiolR . eference t o a l d i t o l d i s u l p h i d e s and s u l -

$ h i d e s i s made i n C h a p t e r 1 d .

1- T h i o - d e r i v a t i v e s

(1)

01’

L-deoxj-4-

3-pliosphono-~-~-ttttradecano~l-2-1(3~S)-~-tetradecanoyloxytetradecanaiiiido] - D - & l u c o s e h a v e b e e n s j r i t h e s i z e d by c o r i v e n t i o r i a l iieaiis ; t h e L ~ r o d u c t as r e d n a l o g u e s oi t n e n o n - r e d u c i n g i i p i d A.

’

sub-unit

of’ b u c t e r i a l

S u b s t i t u t e d methyl and e t h y l L l y c o p S I r a n o s j l t h i o a c r j l -

a t e s ( 2 ) arid ( 3 ) !lave b e e n p r e g a r e d by e i t h e r c o n d e r i s a t i o r i t h i o l ( 4 ) with acetobroinc-ilucose 01’

or -Galactose,

01’

the

or by c o n d e n s a t i o n

t h e b r o u o a l k e n e ( 5 ) w i t h t h e a p p r o p r i a t e 1- f i - t h i o g l y c o p y r a a o s e s .

The a c t i o n o f t h i o l s on t h e f u r a n o s e lorms

reported t o give X-(alkylthio)pentose

01’

t h e i’our D-Gentoses

6

is

d i a l k y l d i t h i o a c e t a l s , a n d 2,5-

Gljcosyl x a n t h a t e s s u c h a s ( b ) h a v e b e e n p r e p a r e d f r o m r e d u c i n g s u g a r

e p i t h i o p e n t o s e d i a l k y l d i t h i o a c e t a l s w i t h i n v e r s i o n a t C-2. d e r i v a t i v e s under phase-transfer

c o n d i t i o n s a s shown i n Scheme 1 .

u e n e r a l l y t h e p r o d u c t s a r e a n o r n e r i c m i x t u r e s b u t t h e c a s e i n Scheme

113

1 I : Thio- and Seleno-sugars

1 gave t h e p-anomer

specifically.

8

sulphone ( 7 ) h a s been i n v e s t i g a t e d .

The r e a r r a n g e m e n t o f t h e b i s -

In pyridine (7) equilibrated t o

a n e q u i m o l a r m i x t u r e o f t h e two f u r a n o s e s ( 8 ) a n d ( 9 ) a n d t h e

a c y c l i c enedisulphone

D-galactose

( 1 0 ) .9

w i t h t h i o a c e t a m i d e g a v e a p r o d u c t w h i c h itas i d e n t i f i e d

a s the thialactone (11). analogously.

T r e a t m e n t o f 2,3,4,5,6-penta-g-acetyl-

10

Other aldehydo-sugars

reacted

iiew s p i r o g l y c o s y i i d e n e h e t e r o c y c l e s h a v e been p r e -

p a r e d from 1 - b r o m o g l y c o s y l c y a n i d e s by t r e a t i n e a t w i t h s u l p h u r nucleophiles. 2-arninoethane

Thus t h e g a l a c t o - b r o m o c y a n i d e ( 1 2 ) o n t r e a t m e n t w i t h 11 t h i o l gave t h e s p i r o t h i a z a n e ( 1 3 ) .

f:>iB, CN

(’2)

4,b-g-Benzylidene

- (-J$-k0

NAc

(’3)

-2-C-tosyl-hex-2-enopyranoses ( 1 4 ) h a v e b e e n

Carbohydrate Chemistry

114 p r e p a r e d r’ro1d t h e c o r r e s p o n d i n k The 3-C-tosyl

L .

sukar.

n i t r o a l k e n e s ( 1 5 ) a s shown i n ScherJe

e r i o l s c o u l r i b e made a n a l o g o u s l j iron1 t h e 2 - n i t r o

An a l t e r n a t i v e a p p r o a c h f o r o b t a i n i n g t h e - 2 - ( ; - t o s y l 12,12 i i i Scherlie 3 .

g o u n d s was v i a t h e e p o x i d e s h o w n

+

*

$T2

, MCPBA

, L U ,MSCL - N E t 3

Ll

W-QpJ

OMe

0 f?e.agents

ph
AT= CbHqMe(f9

0

OH

L, A r S -

~

LL

com-

- OMe SO2 A r

Scheme 3

-

S Na OTf OAc

CH~OAC

(I*>

(’7)

(16)

OAc

‘l’he e t l i j l 1 , 4 - d i t h i o - , x - D - t a l o i u r a n o s i d e

( 1 5 ) has been o b t a i n e d .

4:”)’

06;; yield i ’ r o ~t h e , ! + - u n p r o t e c t e d C-r:iannose d i t h i o a c e t a l was t h e n c o i l v e r t e d t o t h e m e t h j l 6 1 g c o s i d e (21 ) (Scht!nie 4 ) . i! iiew r a d i c a l - c a t a l y z e d 2 , S - r e a r r a n t e m e n t oi’ c j c l i c t h i o n o c a r b o n a t e s ill

t o y i e l d t h i o s u G a r s h a s been d e s c r i b e d ; 3-zalactopyranoside

thus methyl 2,o-di-g-acet~’l-

3,h-cyclothionocarbonate ( 2 2 ) , o n t r e a t m e n t w i t h

t r i b u t j l t i n h ~ d r i d e - a l u r ! i i n i u n I ~b o r o n i t r i d e , of t h e 3 - t h i o c a r b o n a t e

y i e l d e d a 1 :1 m i x t u r e

( 2 3 ) and t h e 4 - t h i o c a r b o n a t e

( 2 4 ) , while t h e

I I : Thio-and Seleno-sugars

115

5,6-thionocarbonate ( 2 5 ) gave a 5:3 mixture of 5-thiogluco-(26) and 5-thioido-(27 c clic carbonates. The mechanism proposed is shown I b , 1s; in Scheme 5.

+

Scheme 5

Ou3Sn-

The first example of a naturally-occurring 5-thiosugar has been reported when 5-thio-D-mannose was isolated from the marine sponge 18 Clathria pyramida. In an effort to understand the origins of the greater sweetness of the thiopyranoid-ring analogues 5-thio-KD-glucopyranose and 6 - t h i o - , 3 - D - f r u c t o p y r a n o s e over (A-D-glucopyranose and p-D-fructopyranose, ab initio quantum mechanical calculations (LCAO-gO at the ST0-3G level) have been performed on these four compounds, and discussed in terms of the calculated net atomic charges. l 9 Acetonation of 5-thio-D-glucopyranose and -D-altropyranose gave the d i - i s o p r o p y l i d e n e - 5 - t h i o - f u c a n o s e derivatives (28) and ( 2 9 ) respectively, as the thermodynamic products, while 5-thioD-allopyranose gave the 2,3:5,6-diisopropylidene compound ( 3 0 ) . The 20 pyranose 2,3:4,6-diacetals were the kinetic products. Both sulphonate groups of methyl 2,3-anhydro-4,6-di-Q-mesyl-5-thio-d-Dallopyranoside (31) readily undergo displacement reactions with nucleophiles; the A-g-rnesyl group is more reactive and is displaced

OH (29)

Ox'

(30)

with retention of configuration, suggesting that participation of the ring sulphur is taking place (Scheme 6). In support of this the thio-

Curbahydrate Chemistry

116

furanosides (32) were isolated and evidence of the ring expanded product (3 ) from treatment of (31) with methanol-barium carbonate wa 31 presented. A 5,6-epithio analogue (34) of 2-acetylmuramyl dipeptide has been synthesized from the 1,2-oxazolidino-D-glucofuranose (35) in several 22 steps. The first naturally occurring analogue (36) of methylthioMe0

QOM

Me0

0

Scheme 6

C 1-12 5 Me

Wd

Ph

(3 MeCHCONHCHCOZH

(35) W e C H C 0 2 H

adenosine has been isolated from the digestive glands and mantles of the marine nudibranch Doris verucosa. 23 5l-S-(5-Acetamido-3,5dideoxy-D-glycero-~-D-galacto-2-nonulopyranosylonic acid)-5'-thiocytidine and its p-anomer have been synthesized by coupling the sodium salts (37) and (38) with 5'-bromo-5'-deoxy-cytidine derivat24 ives ( 3 9 ) . Standard reactions have been used to convert D-glucitol to bis(6deoxy-0-glucitol) 6,6'-disulphide and the corresponding 6,6'-sulphide 25 Methyl 2-n-octanoylamido- and n-dodecanoylamido-2-deoxy6-thio-6-D-glucopyraosides have been prepared by standard reactions from g-acylamidoglucose analogues. The paper also describes the 26 The two epimeric preparation of the b,b'-disulphide (40). 27 acetamido-b-thiosialic acids ( 4 1 ) and (42) have been synthesized.

.

k0Ac

AcO

OAc

(39)

I I : Thio-and Seleno-sugars

117

Selenoglucosinolates ( 4 3 ) and ( 4 4 ) have been synthesized from the corresponding selenourea derivative ( 4 5 ) .

28

References

1 2 3

4 5 b

Z.J.Witczak, E. Carbohydr. Chem. Biochem., 1966, 44, 91. A.Lebouc, J.Simonet, J.Gelas, and A.Dehbi, Synthesis, 1987, 320 (=. Abstr. 1987, 1 0 7 , 14 512). B.Kajanikanth and &.Seshadri, Tetrahedron Lett., 1987, 2 , 2295. F.J.L.Aparicio, F.Z.Benitez, F.S.Gonzalez, and J.L.A.Rosel1, Carbohydr. Res., 1987, 163, 29. Y.Ogawa, Y.Yujishima, I.l(onishi, f.i.Kiso, and A.Hasegawa, J. Carbohydr. Chem., 1987, 2, 399. K.Peseke and A.Merber, Chem., 19bb, 6 , 98 (Chem. Abstr., 1967,

106, 150

7 8

9

z.

778).

K.Blumberg and T.Vanes, 2. A f r . J. Cheni., l9d0, 2 ,2U1 Abstr., 19b7, 127, 134 558j. W.Szeja and J.Bogusiak, Carbohydr. k, 1987, 170, 235. J.G.buchanan, A.K.Edgar, and K.J.dutchison, Carbohydr.

(M.

w, 1987,

ILL),

4UY.

w,

1U L.Somogyi, Carbohydr. 1967, L o , 166. 11 L.SoixaK, b.Batta, I.Farkas, L.Parkanyi, A.Kalman, and A.Somogyi, J. Chem. Synop., 1986, 4% (Chem. Abstr., 1987, u 7 , 154 000). 1 2 -hakibara, I.'l'aKai, 1 .Tachinori, H.'lamamoto, Y.Ishido, and R.Sudoh, Carboiiydr. k, 1987, l o U , C 3 . 12 'l'.Sai
m.

w,

14 U.Kanie, J.Nakamura, Y.ltoh, h.l(iso, and A.hasegawa, 2. Carbohydr. Chem., 1987, 2, 117. 15 d.Classon, ~'.J.baregg, B.Samuelsson, and Z.Liu, J. Carbohydr. Chem., 1987, 2 , 593. l o Y.'l'suda, K.Kanemitsu, K.ka~imoto, ana T.Ki~uchi,Chem. Pharm. Bull., 1987, Yg, 2148. 17 i.Kaiiernitsu, Y.Tsuda, h.E.Haque, K.Tsubono, and T.l(ikuchi, Chem. Pharm. bull., 1987, 35, 3074. 18 ii.J.Capon and J.K.MacLeod, J. Chern. SOC., Chem. Commun., 1987, 1200. 14 R.J.Woods, V.H.Smith, k.A.Szarek, and A.Farazde1, J . Chem. SOC., Cnem. Commun., 1987, 937. LC) EL.Al-ivlasoudi and N.A.Hughes, J. Chem. SOC., Perkin Trans. I, 1987, 1413. L l N.A.L.Al-Masoudi and N.A.Hughes, J. Chem. SOC., Perkin Trans. L, 1987, ~ U o l . LL K.Adlgasser, Ii.honig, and K.Zenk, Liebips Ann. Chem., 1907, 263.

118

Carbohydrate Chemistry

23 b.Cimino, A.Crisyino, S.de Stefano, M.clavaynin, and G.Sodano, Experientia, lYdb, 42, 1301 (Chem. Abstr., 1987, lL6, 99 b4U). 24 O.Kanie, J.1Ja~amura, M.Kiso, and A.dasegawa, J. Carbohydr. Chem., 1987, 4, 105. 25 J.R.banie1, A.V.dahman, and P.L.hchistler, J. Chem. SOC. Pal;., 198b, b , 141 (Chem. Abstr., 1487, lL7, 23 b24). h 1.Yernandez-Bolanos, I .ivIaya C a s t i l l a , and J .Pernandez-Bolanos Guzman, An. y u i n . , Ser.C, 14&, 8 2 , 200 (Chem. Abstr., 1967, lu7, 154 044). 27 d.~*mc#and K.brossmer, I'etrahedron L e t t . , 1967, 2, 191. ~b A.I(jaer and T.Skrydstrup, Acta Cliem. Scand., Ser.b, 19tr7, 4 l , 25).

-

12 Deoxy-sugars

The conformation of digitoxose (2,6-dideoxy-D-ribo-hexose) groups in solutions of digitoxin has been determined to be ‘C1, and the implications for receptor binding discussed.’ The l3C-n.m.r. spectra of the ring forms of digitoxose in DMSO-d6 solution have 2 been fully assigned. The eight possible monodeoxy-analogues of methyl B-maltoside, and also the 6 , 6 ’ - and 1,2-dideoxy-analogues, have been synthesized using a range of conventional deoxygenation methodologies. Their conformations were determined by n.m.r. spectroscopy, and they were tested as substrates for amyloglucosidase; hydroxy groups at 3, 4 ’ and 6 ’ were found essential for substrate activity. 6-Deoxy-D-allo- and -L-talofuranose were obtained by reduction (LiA1H4) of the C - 5 epimeric epoxides (1) available from 1,2:5,6-di0-isopropylidene-a-D-glucofuranose. An epoxidation and reduction sequence applied to the unsaturated sulphone (2) (see Chapter 11) yielded the 3-deoxy-2,3-dideutero-D-arabinoside (31, whereas reaction of the epoxide (4) with methylmagnesium iodide led to the 3-deoxy-2-uloside (5) (Scheme 1) Selectively alkylated and

.

O

OAc b O+o

-x’

(5) 0

acylated derivatives (6) - (9) of L-digitoxoside have been synthesmethylation and reduction ized either from the epoxide (10) (LiAlH4), or from the enone (11) via Michael addition - reduction (Scheme 2). While the cyclic carbonate (12) yielded a mixture of 3- and 4-carbamoyl derivatives on reaction with methylamine, only one product, ( 7 1 , was obtained when this mixture was methylated. 1 Phase transfer catalyzed alkylation of diol (13, R =Bn) gave a 6 mixture of 4- and 3-benzyl ethers, ( 8 ) and ( 9 ) , in the ratio 3 : l .

Carbohydrate Chemistry

120

( 6 ) R'=

H,

R'=

M e OoCO-*

(7) R1= M e , R2=

MeNHM+

(1 0)

('9 R eag ents

L~ R'O

H - R'0

,

R ' = Dn

Na ,L, N a5Hq- McOH w, N aOMe

V, M e N H Z , vi, M e I - A g 2 0 - D M F , v L ,B u q N B r -

3

M &OH , LV, CO CL, - Py ,

(91

(6)

BnBr- NaOh-Hto

Scheme 2

Radical chemistry continues to be widely applied in the synthesis of deoxy-sugars. Reviews entitled "Radical reactions in organic chemistry" and "Tri-n-butyltin hydride as a reagent in organic synthesis"' have included numerous examples of the synthesis of deoxy-sugars by deoxygenation (thiocarbonyl derivatives), deamination, dehalogenation and denitration. Details on the synthesis of deoxy-sugars by regioselective thioacylation (Bu2Sn0 then PhOCSCl), acetylation, and radical deoxygenation (Bu SnH) 3 (see V01.20, p.123) have been published in full,9 while the behaviour of methyl 3,4-g-thionocarbonyl-B-L-arabinoside (14) with tributyltin hydride has been investigated in detail (Scheme 3). The major 3- and 4-deoxy-productsy (15) and (16), are accompanied by minor products (17) - (20). In the presence of excess hydride, the 3,b-g-methylidene derivative (17) predominates (75% yield). If air is bubbled into the reaction mixture, the carbonate (18) becomes

04)

('5)

(9

(1 7)

(1 8)

09)

Reagents. L, 1 3 ~ ~ 5 -t -A1I B~N - tolucne, 75Oc

Scheme 3

the almost exclusive product . l o Deoxygenation via thiocarbonyl ester derivatives has been central to syntheses of benzyl 2,4diacetamido-2,4,6-trideoxy-ay~-D-galactopyranoside (Chapter 9 ) , 2',3'-dideoxycytidine analogues (Chapter 20), and 3-deoxy-D- and L-erythro-pentofuranose derivatives used as intermediates in the total synthesis of amphoteronolide B (Chapter 24).

(2 0)

12: Deoxy-sugars

121

A novel radical rearrangement has been postulated to account f o r the conversion of 2-~-acyl-glucosyl halides, e.g., (211, to the corresponding 2-deoxy-sugars (22) (Scheme 4). To minimize direct reduction o f halide (21) high dilution conditions were employed, Reductive radical with addition of hydride over a 12h period." CH~OAC

(21) OAc R e a g w ~ k s:

L,

OAc

(221

Bu3SnH - A l D N

Scheme

4

debromination has been employed in the construction of 2-deoxypyranosides and disaccharides using the y-iodosuccinimide - alcohol glycosylation procedure (Chapter 3 ) , and in the construction of trisaccharide units of the aureolic acids (Chapter 4). A new approach to 2-deoxyglycosides, including disaccharides, involves the addition of sulphenate esters (ROSPh) to glycals, and subsequently desulphurizing the adducts (Scheme 5). Ratios of 12 B:a-anomers, (23) and ( 2 4 1 , ranged from 1.5 - 4:l.

Specifically deuterated ascaryloses (3,6-didecxy-L-arabinohexoses) (25) - (27) have been synthesized from L-rhamnose, via either the a,B-unsaturated lactone (28) or the benzylidene acetals (29) (Scheme 6). 3-Deoxy-D-gluco-heptono-l,4-lactone tetrabenzoate has been prepared from D-glycero-D-gluco-heptono-lY4-lactone pentabenzoate using the hydrogenolysis procedure of Bock et al. (H2-Pd/C-Et 3N-EtOAc ; Vol. 15 , p. 153) , and reduced (BuiAlH) to provide some of its furanose derivatives [e.g., (3O)l including the free sugar, 3-deoxy-D-gluco-heptose .l4 2 ,6-Dideoxy-L-arabino-hexose (31) and some derivatives have been synthesized from 6-deoxy-Lglucal utilising methoxymercuration, or via 1,2-dibromo-1,2,6trideoxy-L-glucose obtained from a hexonic acid precursor. 15

Carbohydrate Chemistry

122

"Q"' 0

0

Ph (29)

'f'H V U , LY

(26) X = Y = H , Z = D (27) X=Z=H,Y=D Z

OH

(25) X = Y = D , Z = H

The f o u r p o s s i b l e [ l - l j C I - e n r i c h e d o b t a i n e d by a d d i t i o n o f [13C1-cyanide

5-deoxy-L-pentoses

t e t r a a c e t a t e c l e a v a g e o f a p p r o p r i a t e 6-deoxyhexoses, m i x t u r e s o f C-2 deoxy-D-pentoses

have been

t o t e t r o s e s p r e p a r e d by l e a d

epimers being produced.

separable

The f o u r u n e n r i c h e d

5-

were p r e p a r e d from s e l e c t i v e l y p r o t e c t e d p e n t o s e s ,

5 - d e o x y - D - r i b o s e was o b t a i n e d by 5 - d e o x y g e n a t i o n o f m e t h y l 2,3-~-isopropylidene-~-D-ribofuranoside,a n d e q u i l i b r a t e d w i t h 516 d e o x y - D - a r a b i n o s e i n t h e p r e s e n c e of a m o l y b d a t e c a t a l y s t . F u r t h e r i n t e r c o n v e r s i o n s of 2,6-dideoxy-sugars (V01.20, p . 7 9 ) h a v e b e e r , r e p o r t e d . The t r i f l a t e ( 3 2 ) r e a r r a n g e d a t room t e m p e r a t u r e t o t h e o r t h o e s t e r ( 3 3 ) which h y d r o l y s e d t o g i v e t h e e x p e c t e d m i x t u r e of D-lyxo-monobenzoates, o r underwent n u c l e o p h i l i c d i s p l a c e m e n t a t C-3 to p r o v i d e t h e D - x y l o - m o n o b e n z o a t e ( 3 4 ) (Scheme 7 ) . 17 e.g.,

Many r e p o r t s h a v e a p p e a r e d o n t h e s y n t h e s i s o f c h i r a l d e o x y -

123

12: Deoxy-sugars

s u g a r s from non-carbohydrate e l a b o r a t e d 3- or 4 - c a r b o n

start,ing materials.

Five groups have

c h i r a l synthons.

The s y n t h e s i s o f m e t h y l 4 - d e o x y - h e p t o s i d e h y d r o x y l a t i o n o f t h e dihydro-2H-pyran

cis-

s t e r e o i s o m e r s by

type [4+2]-cycloadducts

from

w i t h l-methoxy-1,3-butadiene Chelation ( c . f . , Vo1.19, p . 1 2 4 ) , h a s been f u r t h e r d e t a i l e d . ' *

2,3-~-isopropylidene-D-Rlyceraldehyde

c o n t r o l l e d a l l y l a t i o n of L-lactaldehyde access t o L-rhodinose

d e r i v a t i v e (35) provided

( 3 6 ) and a 4-protected

derivative (37) Alternat-

r e q u i r e d f o r a s y n t h e s i s o f s t r e p t o l y d i g i n (Scheme 8 ) . I 9

i v e a d d i t i o n t o t h i s aldehyde

(35) o f o x y g e n a t e d (E)- or ( Z ) - a l l y l

boron reagents provided t h e isomeric alkenes (38) r a t i o s shown (Scheme 9 ) .

-

( 4 1 ) in t h e

A f t e r chromatographic s e p a r a t i o n t h r e e of

t h e p r o d u c t s were t r a n s f o r m e d i n t o t h e c o r r e s p o n d i n g methyl 2,6-

dideoxy-L-arabino-,

L-ribo-,

and L-lyxo-hexopyranosides

b e n z y l a t i o n - h y d r o b o r a t i o n (g-BBN)-oxidation methanolysis sequence.

by a

(PCCI-deprotection-

20

I n t h e a d d i t i o n o f a l l y l t r i m e t h y l s i l a n e t o t h e aldehydo-Le r y t h r o s e d e r i v a t i v e ( 4 2 ) , a v a i l a b l e from D-glucose

via 1,3-0-

ethylidene-L-erythritol, c h e l a t i o n o f t h e c a t a l y s t (MgBr2) i n v o l v i n g t h e a-benzyloxy-group

ensured high s e l e c t i v i t y (>98$) i n favour of

t h e L - a r a b i n o - p r o d u c t ( 4 3 ) . O z o n o l y s i s t h e n p r o v i d e d 2-deoxy-Larabino-hexose. 2-Deoxy-L-xylo-hexose was s i m i l a r l y s y n t h e s i z e d w i t h h i g h s e l e c t i v i t y ( 9 8 % ) from t h e analogous aldehydo-L-threose d e r i v a t i v e , a v a i l a b l e i n 4 s t e p s f r o m d i e t h y l L - t a r t r a t e .21 The 4-deoxy-D-arabino-hexose d e r i v a t i v e ( 4 4 ) h a s b e e n s y n t h e s i z e d f r o m

Carbohydrate Chemistry

124

t h e (R)-B-ketosulphoxide acetic acid.

(45), a v a i l a b l e i n 4 s t e p s from a-bromo-

The s y n t h e s i s (Scheme 1 0 ) f e a t u r e d a d i a s t e r e o s p e c i f i c

one c a r b o n h o m o l o g a t i o n ( s t e p i i ) . The p r o d u c t was f u r t h e r c o n v e r t e d i n t o t h e C-1 t o C-12 u n i t (46) o f a m p h o t e r i c i n B. 22 YHO

D e t a i l s on t h e s y n t h e s i s o f L - c h a l c o s e and its D-enantiomer

via

S h a r p l e s s e p o x i d a t i o n of a racemic d i v i n y l g l y c o l d e r i v a t i v e

(V01.20, p.127) h a v e b e e n p u b l i s h e d i n f u l l , a n d t h e methodology h a s b e e n e x t e n d e d t o p r o v i d e t h e 4,6-dideoxy-L-lyxo-hexose d e r i v a t i v e (47) from t h e r a c e m i c monobenzyl e t h e r (48) (Scheme 11).23

E- +L

H 6-7

H Me

Me

(48)

Rengeds :

6,Ti (OPrL)+- d-1

L- b?trate- ButO;lH

;u , Red- AL ; iii, O3 -M+

Scheme 11

Two d e o x y - s u g a r s y n t h e s e s h a v e employed e n z y m a t i c p r o c e d u r e s t o 2Deoxy-D-erythro-pentose (49) was s y n t h e s i z e d from c h l o r o f u m a r i c c o n v e r t racemic s t a r t i n g materials i n t o c h i r a l i n t e r m e d i a t e s .

a c i d (5O), e m p l o y i n g m o b i l i z e d f u m a r a s e enzyme t o p r o d u c e t h e d i a c i d (51) i n 2 99.5% e e on a 50g s c a l e (Scheme The 4-deoxy-D-lyxo-hexose

( 5 2 ) was o b t a i n e d

via

diastereospecific yeast

r e d u c t i o n o f t h e m i x t u r e o f f o u r d i a s t e r e o i s o m e r s ( 5 3 ) , which g a v e t h e p u r e i s o m e r (54) i n 20% y i e l d (Scheme 1 3 1 . ~ D ~ e t a i l s on t h e

12: Deoxy-sugars

125

Scheme 12

ex

(53)

synthesis of enantiomeric boivinose (2,6-dideoxy-xylo-hexose) derivatives utilizing an enantioselective enzymatic hydrolysis of a racemic pair of epoxides (V01.20, p.128) have been published in 26 full.

References 1 2 3 4 5 6 7 8 9 10

11 12 13

14 15

R-Hintsche and R.Megges, Z. Chem., 1986, 26, 439 (Chem. Abstr., 1987, 107, 237 150). B.COxon, Magn. Reson. Chem., 1986, 24, 1008 (Chem. Abstr., 1987, 107, 134 557). K.Bock and H.Pedersen, Acta Chem. Scand., Ser. B , 1987, 41, 6 7. V.Zsoldos-Mady and E.Zbira1, Monatsh. Chem., 1986, 117,1325 Chem. Abstr. , 1987, 107, 134 560). T.Sakakibara, 1-Takai,Y.Tachimori, A.Yamamoto, Y.lshido, and R.Sudoh, Carbohydr. Res. , 1987, 160,C3. S.K;pper and J.Thiem, J. Carbohydr. Chem., 1987, 6, 57. M.Ramaiah, Tetrahedron, 1987, 43, 3541. W.P.Neumann, Synthesis, 1987, 665. M.E.Haque, T.Kikuchi, K.Kanemitsu, and Y.Tsuda, Chem. Pharm. Bull., 1987, 35, 1016. K.Kanemitsu, Y .Tsuda, M.E .Haque, K.Tsubono, and T.Kikuchi, Chem. Pharm. Bull. , 1987, 35, 3874. B.Giese, K.S.Gr&inger, T.Witse1, H.-G.Korth, and R.Sustmann, Angew. Chem. Int. Ed. Engl., 1987, 26, 233. Y.Ito and T.Ogawa, Tetrahedron Lett., 1987, 28, 2 7 2 3 . O.Han and H.-W.Liu, Tetrahedron Lett., 1987, 28, 1073. L.O.Jeroncic, A.Fernandez Cirelli, and R.M.de Lederkremer, Carbohydr. Res., 1987. 167, 175. R.A.Ga&kidze and Chan Van Tan, Soobshch. Akad. Nauk. Gruz. SSR, 1986, 124, 529 (Chem. Abstr., 1987, 107,217 940).

126 16 17 18 19 20 21 22 23

24 25 26

Carbohydrate Chemistry J.R.Snyder and A.S.Serianni, Carbohydr. Res., 1987, 163,169. R.W.Binkley and M.A.Abdulaziz, J. Org. Chem., 1987, 52, 4713. J.Jurczak, T-Bauer, and J.Kihlberg, Bull, Pol. Acad. Sci., Chem., 1986, 321 (Chem. Abstr. , 1987, 107,59 352). R.H.Schlessinger and D.D.Graves, Tetrahedron Lett., 1987, 28, 4381. R.W.Hoffmann, R.Metternich, and L.W.Lanz, Liebigs Ann. Chem., 1987, 881. D.R.Williams and F.D.Klingler, Tetrahedron Lett., 1987, 28, 869. G.Solladie and J.Hutt, Tetrahedron Lett., 1987, 28, 797. U.Kufner and R.R.Schmidt, Carbohydr. Res., 1987, 161,211. M.A.Findeis and G.M.Whitesides, J. Orq. Chem., 1987, 52, 2838. G.Fronza, C.Fuganti, P.Grasselli, and S.Servi, J. O r g . Chem., 1987, 52, 2086. P.L.Barili, G.Berti, G-Catelani, F.Colonna, and E.Mastrorilli, J. Org. Chem., 1987, 52, 2886.

13 Unsaturated Derivatives Glycals

1

Reaction o f otherwise protected furanose and pyranose 1,2-diols with methanesulphonyl chloride and triethylamine, followed by treatment of the resulting 2-2-mesylaldosyl chlorides with excess

of active zinc dust and iodide ion,gave the corresponding 1 substituted glycals in high yields. Specifically, "L-digitoxal" (1) has been made by selective reduction of the corresponding 3-one and, more efficiently, from the corresponding 2,6-dideoxy free sugar via its benzoylated qlycosyl chloride.

Various 3-0- and 4-2-substituted derivatives

QH

THPO

(4)

(e.g., benzyl, ally1 ethers) were prepared by selective substitution 2 Selective

using phase transfer and stannylidene-dependent methods.

deacetylation o f 3,4-di-g-acetyl-D-xylal can b e effected with hydrazine acetate in DMF to give 62% of the 3-acetate (21, whereas selective acetylation of D-xylal to give the 4-isomer (3) in 45% yield can be carried out with acetyl chloride in dichloromethane 3 and pyridine. D-Glucal and D-galactal, on reaction with t-butyldimethylsilyl chloride, selectively give the 3,6-disubstituted ethers and hence a route to 4-substituted derivatives, e.g.,

(4).

Compound ( 5 1 ,

derived from the D-glucal diether, was used as a glycosylating 4

reagent to obtain the disaccharide derivative ( 6 ) . A

new method for preparing 2-amino-2-deoxy glycosides is

illustrated in Scheme 1 and can be applied with furanoid derivatives

Rooo - OMe

128

Carbohydrate Chemistry

6) CHiOR

CH20R

---L.-+

ii-iv

RO

RO

BnO-5,

/N

\N

F O /

B "

NHAc

0 R e a g d s : i, B n O 2 C N = N C O 2 B n ; hv ; k , M e O H - H + ; & , H , - P d f C ; i v , A c 2 0

Scheme, 1

to give analogous 2,3-trans-related products. Work on the [ 2 + 2 1

5

cycloaddition of active isocyanates to glycals

to give B-lactams has been reviewedI6 and the authors have also described the preparation of adduct (7) and its conversion into

-

X . .

UH

(7)

R a g e d & i, I O + - ; U ,


\

I

0"

OH

3

CH20H

" O C H 2vY ) NmHC03 ;.u&, N a B H 4

Scheme 2 enantiomerically pure monocyclic compounds as indicated in Scheme 2. They also identified routes to 1-oxapenams and 1-oxacephems, 7 e.g., (8).

Cycloaddition of trichloroacetyl isocyanate to L-rhamnal diacetate gave the products ( 9 ) - ( 1 1 ) , and (9) reacted with alcohols (including carbohydrate alcohols) a s shown in Scheme 3.

8

13: Unsaturated Derivatives

129

2-Deoxy-2-C1*F1f luoro-D-galactose has been made by treating tri-2-acetyl-D-galactal with labelled acetyl hypofluorite followed by acid hydrolysis of the product.’

The unlabelled reagent gave

mixtures o f 1 , 2 - ~ - r e l a t e d - 2 - d e o x y - 2 - f l u o r o p e n t o p y r a n o s y l acetates with acylated pentopyranose glycals, b u t in the furanoid series the direction of addition was controlled by the orientation 10

and nature o f the C-3 substituent as illustrated in Scheme 4.

Photochemical cycloaddition of acetylene to the appropriate enone gave in excellent yield the cyclobutene (12) which was characterized by x-ray analysis

-

II

but no data were given.

(c.f. M.Fetizon et al.,Tetrahedron

Lett., 1986,

21, 1 7 7 7 ) .

The

enone ( 1 3 ) and the 2-ene (14) were amongst the products of treatment CH20Ac

UAC -

AcO

\

OAc

0

(14)

of 1 , 3 , 4 , 6 - t e t r a - ~ - a c e t y l - ~ - D - m a n n o s e2-triflate with tetrabutylammonium fluoride in benzene.

With this reagent the ene

( 1 4 ) reacted further to give the enone (13).

12

An extensive study of the reactions of unsaturated hexopyranosyl derivatives with lithium dimethylcuprate revealed that S 2 and anti-SN2’ products were obtained (see Chapter 14).

Tri-g-acetyl-D~

glucal gave mainly the S 2 product as indicated in Scheme 5.

13

the other hand, this glycal, converted into a palladium-complex intermediate and treated with the organomercurial ( 1 5 1 , gives a range of products, e.g., (16)-(19).

The rationale for these

On

Carbohydrate Chemistry

130 products is given in a lengthy paper.

14

In the area of 2-hydroxyglycal chemistry the D-glucose derived (20) can be converted with equimolar amounts of alcohols and (probably HI in effect) into (21).

catalytic N-iodosuccinimide

With larger proportions of alcohols enones (22) are produced Other hydroxyglycal esters behaved similarly

(Scheme 6 ) . (c. f.

17, p.87, 127) .15

Vol.

enopyranoside

+

A

related hydroxyglycal

hex-2-

enone sequence occurs with lithium

cyanomethylcuprate, the enone undergoing a Michael addition step (See Chapter 14).

A

further reaction o f this type occurred when

Go.-

CH~OAC

CH~OAC

Q

AcO

AcO

OAC

(20) Reagents.

i, N I S - R O t l ( l

(2

iV,

~ U I V ) ;

'I

CH~OAC

0

QR

OAc

(22)

NIS- ROH ( e ~ c e ~ b )

Scheme 6

the isopropyl compound (21) was treated with lithium aluminium hydride; the enone product (22) (R=Prl) underwent carbonyl reduction to afford the 3 , 4 - d i d e o x y - D - e r y t h r o - h e x - 3 - e n o p y r a n -

o side. 15*

The previously known enone (23) has now been made by an

improved process (65% yield) from D-glucose (via the 2-oximointermediate)16 and has been used in the synthesis of (s,S)bissetone (Chapter 24).

The racemic enone (24) has been made as indicated in Scheme 7 and used in the synthesis of the polypropionate chain of Rifamycin S (Chapter 24).

17

131

13: Unsaturated Derivatives 2

Other Unsaturated Derivatives

The unusual cystalline hydroperoxide ( 2 6 ) can be made either by treatment o f tri-2-acetyl-D-glucal (25) with acidic hydrogen peroxide18 or from the ethyl glycoside (27) using hydrogen peroxide and catalytic molybdenum trioxide (Scheme 8) .19

In the latter case

(26)

(27)

Scheme 8

the 2 , 3 - d i d e o x y - B - h e x o p y r a n o s y l product,

hydroperoxide was formed as a by-

Several other 2,3-unsaturated glycosyl hydroperoxides were

described in these papers; they are readily reducible to the corresponding 2,s-unsaturated lactones.

Diels Alder chemistry ha5 20

been used to obtain the glycosides (28) (Scheme 9).

A novel synthesis o f hex-2-enopyranosyl glycosides, including

dissacharide derivatives, involves standard.rearrangement of tri-O-acetyl-D-glucal to give a 1-thiopyridyl compound and subsequent alcoholysis (Scheme 10) .21

In a related paper the phenylthio-

glycoside (29) was also made from tri-2-acetyl-D-glucal and used, by way of a stable C-1 carbanion, to obtain a-C-1 alkylated and 22 acylated derivatives (Scheme 11). Several reference5 are made to other 2,3-unsaturated C-glycosides in Chapter 3.

132

(29) S e q e n t S : i, BwLt ; ii, Me,W; EtOAc, PhCcrO, or (McO),CO

S c h e m e 11 Reactions of 2,3-unsaturated glycosides to have been reported are the high yielding conversion of the glycoside ( 3 0 ) to the transenal (31) (Scheme 12) , 2 3

and the C-5 epimerization of the lactone 24

(32) by application of the Mitsunobu procedure (Scheme 13).

...

(32)

i, M C P B A - BF,.Et,O

; L, L l O H ; iii,P h j P - DE AD - H1O

Scheme 13

The sulphones (33) were obtained from the corresponding 3-nitroalkenes by addition of arylsulphinic acids followed by the elimination of nitrous acid. 2 5 t 2 6

Various reactions of (33) are

illustrated in Scheme 14.25

Its a-anomers can be made from methyl

0 1

S0,Ar

Ph-

,y2

S02Ar VU

( 331

,

.lQMe 0

R v s r . L t s L, N o L ) M e - M e O H , u , N H 3 - H 2 0 - T H F, , U , A C ~ O , WMeNO,-EtjN ,

S c h e m e 14

,v,H1O,-NaOH

,VL,

L t A L D + ; v u , MeMqI

13: Unsaturuted Derivatives

133

2,3-anhydro-4,6-0-benzylidene-a-D-glucopyranoside

by ring opening

with the thiophenates followed by oxidation to the D-altro-sulphones 26 and mesylation of the C-3 hydroxy group. In the area of 3,4-unsaturated compounds, the racemic epimers 27 The 3,4-

(34) and (35) have been made as shown in Scheme 15.

(351 Reogcnts: i , Brz-H1O ;u,I \ l o G H + ; i i i , NaOMe-MedH ;iv, HCL-MeOH

Scheme 15

unsaturated derivative (36) of the fructosyl component of sucrose was obtained following treatment of an epoxide with lithium 28 dimethylcuprate. Reference is made to a Diels Alder adduct of the 3-en-2-one levoglucosenone in Chapter 24, and to the addition with rearrangement of the elements of isobutane to an enolone in Chapter 14. Treatment of the uloside (37) with potassium tert-butoxide followed by methyl iodide affords the rearranged enolone (38).

are also reported in this paper.

Other 3-enes

29

The a- and Bkglycosides (39) have been individually prepared as substrates for a glycosiduronase. 30

Hydrogenation of the enal (40)

gave mainly the L-arabino-aldehyde which could be epimerized in alkali

ko

the D-xylo-analogue.

Reduction of (40) with Bui2AlH was

surprisingly poor yielding and the hydroxymethyl product afforded

134

Carbohydrate Chemistry

the xylo-adduct on hydrogenation

-

against expectations.

31

A method has been reported for the synthesis of 2-alkenes o f the series (41), and related compounds were obtained from 1,2:3,4-di-gisopropylidene-a-D-galacto-dialdose, but extended reaction of this

compound with Wittig

reagent in methanol afforded single adduct 32 Use of

diastereomers (42) (unknown confiquration at C-6).

compounds related to (41) in the synthesis o f antileukemic olguine analogues is referred to in Chapter 5. Compound (43) has been 33 reported, and another 6-ene, used in the synthesis of asperlin, is noted in Chapter 2 4 . Inversion o f configuration at the propargylic centres of the alcohols (44) and (45) has been effected by the Mitsunobu procedure, but attempts to displace corresponding sulphonate esters of the alcohols with sodium benzoate in D M F led to some o f the unusual 34 allenic esters (46).

The acyclic alkene derivative (47) (also a dodec-6-enopyranose derivative) has been isolated from a South African plant and characterized by X-ray cystallography. (For a relevant synthetic study see Chapter 24). 35

Further studies have been carried out on

polysaccharide structures using reductions o f carboxylic acid groups to hydroxymethyl and hence iodomethyl followed by zinc treatment and 36

reduction to afford glycosyl-substituted l I 2 - d i d e o x y h e x - l - e n i t o l s . 2,3-g-Isopropylidene-D-glyceraldehyde

has been used to produce

a

set of branched-chain l 1 2 - d i d e o x y h e x - l - e n i t o l s (Chapter 18) and also some 3,4-unsaturated 1-deoxyketone derivatives as illustrated in 37

Scheme 16.

Knoevenagel reactions have been carried out o n 2,3:4,5-di-g-

isopropylidene-aldehydo-D-xylose with methyl acetoacetate and pentane-2,4-dione and products such as ( 4 8 ) have been obtained.

38

Reactions o f Wittig reagents with carbohydrate aldehydes have been used to obtain access to cyclopentanes (Chapter 18) and an isomer

of Compound (47) (Chapter 24).

13: Unsaturated Derivatives

135

References to unsaturated compounds containing exocyclic double bonds are made in Chapter 14.

References 1

2 3 4 5 6 7 8 9

10

C.W.Holzapfe1, J.M.Koekemoer, and G.H.Verdoorn, S . Afr. J. Chem., 1986, 39, 151 (Chem. Abstr., 1987, 107,134 554). S.Kgpper, I.Lundt, C.Pedersen, and J.Thiem, Liebigs Ann. Chem., 1987,531. S.Bouhroum and P.J.A.Vottero, Tetrahedron Lett., 1987, 28, 5529. W.Kinzy and R.R.Schmidt, Tetr B.J.Fitzsimmons, Y.Leblanc, and J.Rokach, J. Am. Chem. Soc., 1987, 109, 285. M.Chmielewski and J.Jurczak, J. Carbohydr. Chem., 1987, 6, 1. M.Chmielewski, Z.Kaluza, W.Abramski, and C.Belzecki, Tetrahedron Lett., 1987, 2 8 , 3035. M.Chmielewski, Z.Kaluza, D.Mostowicz, C.Belzecki, E-Baranowska, J.P.Jacobsen, P.Salanski, and J-Jurczak,Tetrahedron, 1987, 43, 4555. M.Tada, T.Matsuzawa, K.Yamaguchi, Y.Abe, H.Fukuda, M.Itoh, H.Sugiyama, T.Ido, and T.Takahashi, Carbohydr. Res., 1987, 161, 314. K.Dax, B.I.Glanzer, G.Schulz, and H.Vyple1, Carbohydr. Res., 1987, 162, 13.

Carbohydrate Chemistry

136 11 12 13 14 15 15a 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38

T-Matsui, T.Morooka, and M-Nakayama, Bull. Chem. SOC. Jpn., 1987, 60, 417. R.W.Binkley, M.G.Ambrose, and D.G.Hehemann, J. Carbohydr. Chem., 1987, 6, 203. N.Kawauchi and H.Hashimoto, Bull. Chem. SOC. Jpn., 1987, 60, 1441. J.C.-Y-Cheng and G.D.Daves, J. Org. Chem., 1987, 52, 3083. O.Varela, G.M.de Fina, and R.M.de Lederkremer, Carbohydr. Res., 1987, 167, 187. Y.Ichikawa, M.Isobe, D.-L.Bai, and T.Goto, Tetrahedron, 1987, 43, 4737. M.Brehm, W.G.Dauben, P.Kb;hler, and F.W.Jich-Angew. Chem. , Int. Ed. Engl., 1987, 2, 1271. S.J.Danishefsky, D.C.Myles, and D.F.Harvey, J. Am. Chem. S O C . , 1987, 109, 862. H.-W-Fehlhaber,G-Snatzke,and I.Vlahov, Liebigs Ann. Chem., 1987, 637. M.Chmielewski, J.Jurczak, and S.Maciejewski, Carbohydr. Res., 1987, 165, 111. J.Jurczak and T.Bauer, Carbohydr. Res., 1987, 160,C1. M.K.Gurjar and T.G.Murali Dhar, J. Carbohydr. Chem., 1987, 6, 313. S.Valverde, S.Garcia-Ochoa, and M.Martin-Lomas, J. Chem. SOC., Chem. Commun. , 1987,383. K.S.Kim, K.S.Junq, and C.S.Hahn, Bull. Korean Chem. SOC., 1986, 2, 481 (Chem. Abstr., 1987, 107, 154 615). S.Salverde, S.Garcia-Ochoa, and M.Martin-Lomas, J. Chem. SOC., Chem. Commun., 1987, 1714. T.Sakakibara, I.Takai, Y.Tachimori, A.Yamamoto, Y.Ishido, and R.Sudoh, Carbohydr. Res. , 1987, 160,C3. T.Sakakibara, I.Takai, A.Yamamoto, Y.Tachimori, R.Sudoh, and Y.Ishido, Carbohydr. Res., 1987, 169, 189. R.Bognar, P.Herczegh, M.Zsely, and G.Batta, Carbohydr. Res., 1987, 164, 465, R.Khan and G.Pate1, Carbohydr. Res., 1987, 162, 298. A.Klemer and W-Klaffke, Liebigs Ann. Chern., 1987, 759. N-Otatani and Z.Yosizawa, Carbohydr. Res., 1987, 159, 25. R.M.Giuliano and J.H.Buzby, J. Carbohydr. Chem., 1987, 6, 541. S.Valverde, M.Martin-Lomas, B.Herradon, and S. Garcia-Ochoa, Tetrahedron, 1987, 43, 1895. J.M.J.Tronchet and M.A.M.Massoud, Heterocycles, 1986, 24, 1265 (Chem. Abstr. , 1987, 106, 18944) S.Jarosz, J-Glodek, and A.Zamojski, Carbohydr. Res., 1987, 163,289. M.T.D.Coleman, R.B.English, and D.E.A.Rivett, Phytochemistry, 1987, 2, 1497. G.O.Aspinal1, L.Khondo, and B.A.Williams, Can. J. Chem., 1987, 65, 2069. S.Piku1, J.Raczko, K-Ankner, and J.Jurczak, J. Am. Chem. SOC., 1987, 109, 3981. F.J.Lopez Herrera, M.Valpuesta Fernandez, and R.Garcia Sequra, An. Quim., ~Ser. C., 1985, 81,232 (Chem. Abstr., 1987, 106,102620).

-

.

14 Branched-chain Sugars 1

Comoounds with an R-C-0 Branch

The reaction of Grignard reagents with the sucrose derivatives (1) and (2) has been investigated. Treatment of (1) with nethyl magnesium iodide at - 7 8 O C afforded only ( 3 ) , whereas at room temperature both ( 3 ) and (4) were obtained, and with ulose (2) both (5) and (6) were formed. Ally1 magnesium iodide reacted with (2) to give only Similarly, the addition of organometallic reagents to the (7).' ( I ) Ri,R2=0,

R1 ' 0

0

R4 = COBut Me, R2=OH, R3 = Tr, R4= B n (4) R' = O H , R2 = Me, R3= Tr, R 4 = Bn

CH20R4

CH20R3

b

H

OR^

2

0

R 3 =Tr,R4=Bn

(2) R1, R2 = 0 , ? !:

(3) R'

R

4

OR^

=

(5) R' = M e , R 2 = O H , R:R4 = C O B d (6) R' = O H , R2= Me, R3, R4

=

COBW~

(7) R' = A l l , R2=OH, R3,R4= C o b t

ketone (8) afforded predominantly the products (9) with ribo 2 stereochemistry, whereas the 2-ulose (10) gave exclusively (11). Methyl lithium added stereospecifically to the ketone (12) to give

OH

OH

WW~B" (9) R E Me,Et,

(8)

(10)

(11)

C%CH

Me

R ~ O

a trisaccharide unit lactones spiro-fused Reformatsky reaction Both epimers of each

Me

R ~ O

(12) R',

R ~ O

R~

2 0

(13) R ' = O H ,='A

, R3= 132

Me, R3= H

(13) of the aureolic acids. a-Methylene-yto sugar moieties have been synthesized by a with the corresponding ketones (Scheme 1). 4 product were isolated.

Carbohydrate Chemistry

138

Scheme 1

The b r a n c h e d compounds (14), ( 1 5 ) a n d (16) h a v e b e e n o b t a i n e d from a c o r r e s p o n d i n g b i s - s p i r o e p o x i d e i n t e r m e d i a t e ; a t t e m p t s t o u s e t h e s e t e r t i a r y d i o l s i n tandem w i t h l i t h i u m a l u m i n i u m h y d r i d e for t h e a s y m m e t r i c r e d u c t i o n o f a number o f k e t o n e s g a v e o n l y low optical yields. 5

R

(14) R = M e

0

(15) 9 = Et

O p P h

(16) R = Bn

0

The c o n v e r s i o n o f D-glucose i n t o t h e b r a n c h e d - c h a i n d e r i v a t i v e s (17) and (18) v i a t h e u l o s e (19) a n d t h e W i t t i g a d d u c t ( 2 0 ) has b e e n r e p o r t e d i n an approach t o t h e s y n t h e s i s o f t h e a n t i b i o t i c s A f a c i l e s y n t h e s i s of d e l l e s s e r i n e amipurimycin and miharimycin.

(211, a m a r i n e a l g a l m e t a b o l i t e t h o u g h t t o h a v e a n t i c o a g u l a n t p r o p e r t i e s , h a s b e e n a c h i e v e d by t h e s i m p l e t r e a t m e n t o f 2-2-methylL - a s c o r b i c a c i d w i t h p h y d r o x y b e n z y l a l c o h o l (Scheme 2 ) . S i m i l a r l y , OH HO

Rcageaks :

k

o

HO

OMc

L,

+ CHZOH

H20 ( 5 0 ' ~ )

Scheme 2 t r e a t m e n t of L-ascorbic

acid with t h e benzyl alcohol derivative (22)

139

14: Branched-chain Sugars

afforded a 4:l mixture of (23) and (24), the latter on reduction with diborane giving leucodrin (25), a phenolic constituent of HO I I , .

CH2 CO, Me

(23)

species of proteaceae.7

'4 Po

(24)

OH

HO

(25)

Further work on the alkylation of sugar

enolates has afforded the axial alkylation product (26) from either 3-ulose epirner (27) or (28). Similarly the 2-ulose (29) gave ( 3 0 ) , whereas (31.) gave ( 3 2 ) , and (33) was not alkylated but afforded (34).

8

The known L-rhamnose derivative ( 3 5 ) , which is obtained by methylation of the parent ketone, has been converted into methyl L-sibirosarninide (36) and N-acyl kansosamine (37) by standard The synthesis of 2-C-methyl-D-ribose derivatives rnethodol.ogy. (and related nucleosides) has been reported, utilizing periodate cleavage of 3-C-methyl-D-glucose compounds.l o The known 2-c-( hydroxymethy1)-D-mannose derivative (38) has been converted into 6-deoxy2-g-methyl-D-rnannitol and 2-~-(hydroxymethyl)-D-mannitol, which A new method f o r the were made as potentially sweet compounds." synthesis of D,L-apiose (39) enables the selective preparation o f 2 ( d 3 C ) , and/or ( d 3 C ) , and/or ( 1- H) , and/or (2-*H) enriched 12 derivatives .

140

Carbohydrate Chemistry

OQ"'- 0

0

x (35)

2

Compounds with an R-C-N Branch

The product of periodate cleavage of the fructose derivative (40) has been treated with nitroethane to give (41), (42) and (43) in the ratio of 6:3:1, which on reduction afforded the respective 4-amino-4-g-methyl hexulose derivatives. l 3 Similarly, methyl B-Dglucopyranoside after treatment with periodate and basic nitroethane

gave (44) and (45) in 12% and 9% yields, the latter presumably arising from epimerization of the intermediate aldehyde.l4 The azetidinone (46) (readily available from the cycloaddition of isoprene to chlorosulphonyl isocyanate) has been used f o r the preparation of the 3-C-methyl-3-aminopentoses (47) and (48) in racemic f o r m . 15

Alkylation of the enolate of ketone (49) with methyl iodide afforded both epimers of the C - 3 methyl compound, and these products 16 gave access to L-vancosamine, L-decilanitrose and D-rubranitrose.

14 1

14: Branched-chain Sugars

3

Compounds w i t h a n R-C-H,

A new b r a n c h e d - c h a i n

xylo-hexose

or C=R Branch

R-C-R,

s u g a r , 3,6-dideoxy-4-C-(l-hydroxyethyl)-D-

( y e r s i n i o s e ) , h a s b e e n i s o l a t e d from Y e r s i n i a

e n t e r o c o l i t i c a 0 : 4.32 l i p o p o l y s a c c h a r i d e , I 7 a n a a new a p i o s e c o n t a i n i n g c o u m a r i n g l y c o s i d e h a s b e e n e x t r a c t e d from r o o t b a r k o f Adina C o r d i f o l i a .

The c . i

. mass

s p e c t r a o f some b r a n c h e d - c h a i n

h e x o p y r a n o s i d e s w i t h Ac, C02Me, C O N H 2 or C N b r a n c h a t C-3 as w e l l

as some g e m i n a l d i s u b s t i t u t e d compounds h a v e b e e n r e p o r t e d . 19 I n an e x t e n s i v e review o f r a d i c a l r e a c t i o n s i n o r g a n i c s y n t h e s i s

a number o f e x a m p l e s o f b r a n c h e d - c h a i n s u g a r s y n t h e s i s a r e c o v e r ed.** A r e v i e w o f t r i - n - b u t y l t i n h y d r i d e i n c l u d e s some e x a m p l e s o f 21 branched-chain s u g a r s y n t h e s i s . A n o v e l a t t e m p t t o p r e p a r e t h e w e s t e r n s e c t i o n o f nogalamycin i n v o l v e d t h e c y c l i z a t i o n shown i n Scheme 3 . The y i e l d s w e r e low and e r r a t i c b u t s u g g e s t e d t h e p o s s i b l e s u c c e s s of t h i s approach

Reagent: i , CF3CO$i

Me

Scheme 3

u n d e r o p t i m a l c o n d i t i o n s . 22

T r e a t m e n t o f tetra-g-acetyl-3-deoxy-3-

iodo-B-D-glucopyranose w i t h a l l y l t r i b u t y l t i n g a v e t h e 2 - 3 - a l l y l g l u e 0 compound ( 6 0 % ) a n d i t s C-3 e p i m e r (11%).The m a j o r p r o d u c t

was c o n v e r t e d t o t h e c o r r e s p o n d i n g g l y c o s y l i o d i d e , w h i c h , i n t h e p r e s e n c e o f t r i b u t y l t i n h y d r i d e , a f f o r d e d t h e b i c y c l i c compounds

(50) a n d (51) i n a 9:1 r a t i o , w h e r e a s t h e i o d i d e ( 5 2 ) d i d n o t Me

‘A,

GI

CH*CHzCH=CHz

AcO

OAc

OAc.

OAc

c y c l i z e on f o r m a t i o n o f t h e g l y c o s y l r a d i c a l .23 The c o n j u g a t e a d d i t i o n o f a number o f r a d i c a l s t o a c a r b o h y d r a t e e n o l o n e p r o c e e d e d w i t h good t o e x c e l l e n t d i a s t e r e o s e l e c t i v i t y w i t h c o n c o m i t a n t m i g r a t i o n o f a b e n z o y l g r o u p (Scheme

4). 24

142

Carbohydrate Chemistry

(53) by t r i b u t y l t i n h y d r i d e g a v e a

Deoxygenation of t h e x a n t h a t e

12:l m i x t u r e o f ( 5 4 ) a n d ( 5 5 ) .

The same m i x t u r e was o b t a i n e d b y

d e r i v a r ; i v e (56) u s i n g ( C p ) Z r H 2 (44) a n d ( 4 5 ) o n t r e a t m e n t w i t h

h y d r o z i r c o n a t i o n of E - m e t h y l e n e

C L * ~ The n i t r o - c o m p o u n d s

Me

(54)

(53) R = CS2Me

(55)

t r i b u t y l t i n h y d r i d e g a v e m i x t u r e s o f t h e c o r r e s p o n d i n g 3-deoxy-3-Cm e t h y l compounds.

14

I n a s t u d y o f t h e C l a i s e n r e a c t i o n a p p l i e d t o a number o f c a i - b o h y d r a t e d e r i v a t i v e s , t h e a l l y l i c a l c o h o l ( 5 7 ) was h e a t e d i n triethylorthoacetate i n t h e presence of propionic acid c a t a l y s t t o a f f o r d t h e d o u b l y - b r a n c h e d compound ( 5 8 ) w i t h h i g h s e l e c t i v i t y t h e i: i s o m e r o f ( 5 7 ) p r o v e d much l e s s r e a c t i v e , g i v i n g u n d e r t h e same c o n d i t i o n s a m i x t u r e o f ( 5 8 ) a n d ( 5 9 ) w i t h u n c h a n g e d s t a r t i n g material.

Alkene ( 6 0 ) and i t s Z i s o m e r u n d e r t h e s e c o n d i t i o n s

(58)

(57)

g e n e r a t e d o n l y (61).

A l a r g e number o f compounds w i t h a d o u b l e

b r a n c h were made a n d c h a r a c t e r i z e d i n t h i s s t u d y . 2 6 used h i s hetero-Diels-Alder branched-chain

Danishefsky has

r e a c t i o n f o r t h e p r e p a r a t i o n of t h e

octo-pyranoside

d e r i v a t i v e ( 6 2 ) and hence t h e

u n d e c o s e (63) (Scheme 5 ) , w h i c h a r e i n t e r m e d i a t e s i n t h e s y n t h e s i s A review on t h e o f t h e polypropionate chain of Rifamycin S.27 h i g h p r e s s u r e C4+21 c y c l o a d d i t i o n o f l-methoxy-buta-lY3-diene t o c a r b o n y l compour!ds,

as w e l l as t h e C2+21 c y c l o a d d i t i o n o f a c t i v e

143

14: Branched-chain Sugars ye

Me

OR

OR

0 Me

0

(631

OBn

OMe

Scheme 5

28 isocyanates t.0 glycals covers mostly the authors ' own work. These same authors have published further work on the C 2 t 2 1 cycloaddition of trichloroacetyl isocyanate to various glycals .29y30 A 1,3-.dipolar cycloaddition of benzonitrile oxide to hex-2-enono-1,5lactone (64) gave (65) and (66), isolated in 58 and 7% yields respectively. 31 The major 1 3-dipolar cycloadduct (67) derived CH~OAC

AcO

-2

-

3

(64)

from the C-4-epimer of lactone (64) was converted by hydrogenation to the branched deoxy derivative (68).32 Photolysis of ( 6 9 ) in lY3-dioxan afforded ( 7 0 ) and (71), while in tetrahydrofuran low Adduct (75) was yields of (72), (73) and (74) were obtained.33

obtained by photochemical addition of acetylene to the correspondjng enone. 34 Conjugate addition by higher order cuprate Me2Cu(CN)Li 2 to enones (76) and (77) gave the 4,4 and 2,2-di-C-methyl-hexopyranosides (78) and ( 7 9 ) respectively. Trapping of the intermediate enol in the formation of ( 7 9 ) as the enol silyl ether and subsequent

Carbohydrate Chemistry

144

h y d r o b o r a t i o n a f f o r d e d , a f t e r a c e t y l a t i o n , t h e 2,2-di-g-methyl-a-Dg l u c o p y r a n o s i d e (80).35

An e x t e n s i v e s t u d y o f u n s a t u r a t e d hexo-

p y r a n o s i d e d e r i v a t i v e s t r e a t e d w i t h l i t h i u m d i m e t h y l c u p r a t e has been r e p o r t e d .

P r o d u c t s d e r i v e d from SN2 a n d a n t i - S N 2 ' r e a c t i o n s

w e r e o b t a i n e d d e p e n d i n g on t h e s u b s t r a t e , e . g . ,

a l l y l i c acetates

(81) a n d (82) a f f o r d e d ( 8 3 ) a n d (84) r e s p e c t i v e l y , w h e r e a s (85) gave ( 8 6 ) . 36

L i t h i u m d i m e t h y l c u p r a t e o p e n i n g o f t h e s u c r o s e epoxide

0

CH2 OTr

CH20Tr

OMe4

QoMe

1

CHZOTr

Me

OAC

(8'

CHzOTr

FEAc +AcOO L~Q~PQ~~~ CH20Ac

(82)

(83)

(85)

(8 4)

(86)

d e r i v a t i v e (87) a n d s u b s e q u e n t a c e t y l a t i o n a f f o r d e d (88).37 fH20Ac

CH2C1

(37)

(99

Condensation o f $-2-benzyloxypropanal

( 8 9 ) with t h e t i t a n i u m

a l k e n e (90) p r o v i d e d a r o u t e t o m e t h y l f u r a n o s i d e s o f u n n a t u r a l

3,6-dideoxy-3-methyl-aldohexoses

(Scheme 6).

Thus (91) a f f o r d e d

145

14: Branched-chain Sugars t h e a-L-allofuranoside

d e r i v a t i v e ( 9 2 1 , a n d ( 9 3 ) g a v e t h e B-L-

t a l o f u r a n o s i d e compound ( 9 4 ) . 3 8 The e n o l a t e ( 9 5 ) , o b t a i n e d by t r e a t i n g m e t h y l 2 , 3 : 4,6-di-~-benzylidene-a-D-mannopyranoside w i t h b u t y l l i t h i u m , was a l k y l a t e d w i t h a c e t a l d e h y d e a n d t h e a d d u c t d e h y d r a t e d t o g i v e enone ( 9 6 ) . c a t a l y s e d hetero-Diels-Alder

T h i s enone undergoes L e w i s a c i d -

reaction with enol ethers, e.g.,

(97) ,

( 4 examples g i v e n ) w i t h t h e f o r m a t i o n of s i n g l e i s o m e r s , e . g . , (98).39

Replacing l i t h i u m i n (95) with zinc gives a b e t t e r

nucleophile a t carbon.

Thus a l d o l c o n d e n s a t i o n s w e r e e f f e c t e d

Ph

EtO

4 Me

(97)

b e t w e e n t h e z i n c e n o l a t e a n d a number o f a l d e h y d e s , g i v i n g a d d u c t s The ( 9 9 ) . E p i m e r i z a t i o n a t C-2 c o u l d b e e f f e c t e d by b a s e . O' e n o l a t e o f methyl 4,6-~-benzylidene-3-deoxy-3-~-methyl-a-D-arabinoh e x o p y r a n o s i d - 2 - u l o s e h a s b e e n t r a p p e d o n o x y g e n [ g i v i n g (loo)], o n c a r b o n [ g i v i n g (1Ol)l a n d s u b m i t t e d t o R o b i n s o n a n n e l a t i o n [ g i v i n p t r i c y c l e (102)l.41 r

\ ?

Me (100) R = Bn or Me3Si

-

3/

0

(101)

The a m i d e ( 1 0 3 ) , d e r i v e d f r o m 2,3-0-isopropylidene-D-,glyceraldeh y d e , was c o n v e r t e d by b a s e t r e a t m e n t i n t o B - l a c t a m ( 1 0 4 ) w h i c h s e r v e d as a p r e c u r s o r t o 2,3-dideoxy-2-amino-3-hydroxymethyl-a-Da a n n o f u r a n o s i d e d e r i v a t i v e s . 42

2-Deoxy-2-~-methyl-D-glucose h a s via t r e a t m e n t o f

b e e n p r e p a r e d f r o m 1,6-anhydro-B-D-glucopyranose

t h e known e p o x i d e ( 1 0 5 ) w i t h m e t h y l l i t h i u m a n d s u b s e q u e n t h y d r o l y s i s . 43

x:bo a H \'"

(103) 0

0

'"/c02E t

Nh

(104)

RO

(105) (r06) f?R == Bn SL$

Carbohydrate Chemistry

146

Further work on "pyranoside homologation" has illustrated its use in producing compounds with multiple chiral centres. Epoxide (106) was transformed y& (107) into the dipyranosides (108) and Further elaboration save tripyranoside (110) which then (109).44

contains 7 of the 8 chiral centres of the ansa chain of Rifamycin S.45 Similarly the epimers (111) were synthesized by way of a

dipyranoside intermediate as a model study of the synthesis of the ansa chain of streptovaricin A. 46 The branched-chain dianhydride (112) has been prepared by hydroboration of alkene (113). The product (114), on treatment with sodium hydride under>goes a silyl migration and generates (112) directly. 47 During attempts to

synthesize the C-5 branched compound (115) stereoselectively it was found that hydrogenation of alkene (116) gave a 1:l mixture of (115) and its C-5 epimer, whereas hydroboration of (117) gave exclusively (115). Compound (115) was supsequently transformed into 1,3,548 trideoxy-3,5-di-~-methyl-L-talitol. 6 CHZOH

'kr o+

(1 15)

~CH~OSL?

(1'

6 CH3

CH,$5"

CH2{S

6)

(117)

14: Branched-chain Sugars

147

Similarly, during a stereocontrolled synthesis of (118) it was found that hydroboration of (119) gave mainly the undesired isomer and hydrogenation of (120) was not selective. However, hydroboration of (120) gave a 96:4 ratio of epimers in favour of (121) which was then transformed into (118).49 Hydroboration of (122) was reported to give (123) s e l e ~ t i v e l y . ~During ~ studies on some C - 4 exocyclic methylene hexopyranoside derivatives, it was found that the stereochemical outcome of hydroboration could be affected by the protecting group on 0-6. Additionally hydrogenation could be controlled to favour either C-4 methyl epimer by choice of catalyst and solvent. 51 Wittig reaction of uloses (124) and (125) gave only (126) from both starting materials as they equilibrate under the reaction conditions. However, olefination of (127) gave (128) which served

(124) R =SL+

(125)

(’24)

(127) R = Si P h Z B 3

as precursor to the fused butyrolactone (129). 52 The known conversion of (130) to (131) (using Me(CN)CuLi) has allowed the synthesis of branched-chain glycal (132) which was converted to synthon (1331, required for a synthesis of okadaic acid.53 Some

branched-chain nucleosides have been mentioned in chapter 20.

148

Carbohydrate Chemistry References

1 2 3

4 5 6

7 8

9

10 11 12 13

14 15 16 17 18 19

20 21 22 23 24 25

26 27 28 29 30 31 32 33 34 35 36 37 38 39 40

A.K.B.Chiu, L.Hough, A.C.Richardson, I.A.Toufeili, and S.Z.Dziedzic, Carbohydr. Res., 1987, 162, 316. K.Krohn, E.Broser, and H.Heins, Carbohydr. Res., 1987, 164,59. J.Thiem, M-Gerken,B.Schottmer, and J.Weigand, Carbohydr. Res., 1987, 164, 327. A.P. Rauter, J.A. Figueiredo , I .Ismael , M.S .Pais, A.G.Gonzalez , J .Diaz , and J.B.Barrera, J. Carbohydr. Chem., 1987, 5, 259. N.Baggett, R.J.Simonds, and P.Stribblehil1, Carbohydr. Res., 1987, 162, 153. K.Hara, H.FuJimoto, K.Sato, H.Hashimoto, and J.Yoshimura, Carbohydr. Res., 1987, 159,65. A.J.Poss and R.K.Belter, Tetrahedron Lett., 1987, 28, 2555. A.Klemer and W.Klaffke, Liebigs Ann. Chem., 1987, 759. J.Yoshimura, A.Aqee1, K.-I.Sato, R.B.Singh, and H.Hashimoto, Carbohydr. Res. , 1987, 166,253. EBeigel'man, M.Ya Karpeiskii , and S .N.Mikhailov, Bioorg. Khim. , 1986, 12, 1359 (Chem. Abstr. , 1987, 107, 176 391). rB.Witczak and R.L.Whistler, Carbohydr. Res. , 1987, 169, 252. J.R.Snyder and A.S.Serianni, Carbohydr. Res. , 1987, 166, 85. F.W.Lichtenthaler, A.Pashalidis, and H.J.Lindner, Carbohydr. Res., 1987, 164. 357. G t a n i and S.Hashimoto, Bull. Chem. SOC. Jpn. , 1987, 60, 1825. F.M.Hauser, S.R.Ellenberger, and R.P.Rhee, J. Ory. Chem., 1987, 52, 5041. A.Klemer and H.wilbers, Liebigs Ann. Chem., 1987, 815. R.P.Gorshkova, V.A.Zubkov, V.V.Isakova, and Yu.S.Ovodov, Bioorg. Khim., 1987, 2, 1146 (Chem. Abstr., 1987, 107,149 641). Y.Asheervadam, P.S.Rao, and R.D.H.Murray, Fitoterapia, 1986, 57, 231 (Chem. Abstr., 1987, 106,99 357). V.I.Kadentsev, I .A.Trushkina, O.S.Chizhov, V.V.Nemal'tsev, and V.A.Afanas' ev, Bioorg. Khim., 1986, 12, 1561 (Chem. Abstr. , 1987, 107,176 334). M.Ramaiah, Tetrahedron, 1987, 43, 3541. W .P .Neumann , Synthesis, 1987, 665. T.H.Smith and H.Y.Wu, J. Org. Chem. , 1987, 52, 3566. K.S Groninger, K. F.Jager, and B Giese , Liebigs Ann. Chem , 1987 , 731. B.Giese and T.Witze1, Tetrahedron Lett., 1987, 28, 2571. N.K.Kochetkov, A.F.Sviridov, D.V.Yashunskii , M.S .Ermolenko, and V.S .Borodin, Izv. Akad. Nauk. SSSR, Ser. Khim., 1986, 441 (Chem. Abstr., 1987, 106, 120 150). K.-i.Tadano, Y.Idogaki, H-Yamada, and T-Suami, J. Org. Chem. , 1987, 52, 1201. S.J.Danishefsky, D.C.Myles, and D.F.Harvey, J. Am. Chem. SOC., 1987, 109, 862. M.Chmielewski and J.Jurczak, J. Carbohydr. Chem., 1987, 2, 1. M.Chmielewski and Z.Kaluza, Carbohydr. Res., 1987, 167, 143. M.Chmielewski, Z.Kaluza, D.Mostowicz, C.Belzecki, E.Baranowska, J.P.Jacobsen, P.Salanski, and J.Jurczak, Tetrahedron, 1987, 43, 4555. H.Gnichte1, L.Autenrieth-Ansorqe, J.Dachmann, P .Lugerr and A.Duda, J. Carbohydr. Chem., 1987, 6, 673. I.Panfi1, C.Belzecki, and M.Chmielewski, J. Carbohydr. Chem., 1987, 5, 463. T.Sakakibara and T-Nakagawa,Carbohydr. Res. , 1987, 163,239. T.Matsui, T.Morooka, and M.Nakayama, Bull. Chem. SOC. Jpn., 1987, 60, 417. N .Kawauchi , K.-i .Sat0, J .Yoshimura, and H .Hashimot0, Bull. Chem. SOC. Jpn. , 1987, 60, 1433. N.Kawauchi and H.Hashimoto, Bull. Chem. SOC. Jpn., 1987, 60, 1441. R.Khan and G.Pate1, Carbohydr. Res., 1987, 162, 298. D.Hoppe, G.Tarara, M.Wilckens, P.G.Jones, D.Schmidt, and J.J.Stezowski, Angew. Chem. Int. Ed. Engl. , 1987, 26, 1034. Y .Chapleur and M.-N.Euvrard, J. Chem. SOC. , Chem. Commun. , 1987, 884. S.Handa, R.Tsang, A.T.McPhai1, and B-Fraser-Reid, J. Org. Chem., 1987, 52,

.

.

.

149

14: Branched-chain Sugars

41 42 43 44 45 46 47 48 49 50

51

52 53

3489. R.V.Bonnert and P.R.Jenkins, J. Chem. SOC. , Chem, Comun., 1987, 6. M.Shiozaki and N.Ishida, Chem. Lett., 1987, 1403. R.Faghih, J. Carbohydr. Chem., 1987, 6, 619. B.Fraser-Reid, L.Magdzinski, B.F.Molino, and D.R.Mootoo, J. Org. Chem., 1987, 52, 4495. B.Fraser-Reid, B.F.Molino, L.Magdzinski, and D.R.Mootoo, J. Org. Chem. , 1987, 52, 4505. D.R.Mootoo and B.Fraser-Reid, J. Org. &em., 1987, 52, 4511. R.Faghih and B Fraser-Reid , Carbohydr Res , 1987, 169, 247. D.Liang, A.D.Schuda, and B.Fraser-Reid, Carbohydr. Res., 1987, 164,229. Y .Oikawa, T-Tanaka,K.Horita, I .Noda, N.Nakajima, N-Kakusawa,T.Hamada, and O.Yonemitsu, Chem. Pharm. Bull., 1987, 35, 2184. T.Tanaka, Y.Oikawa, T.Hamada, and O.Yonemitsu, Chem. Pharm. Bull., 1987, 35, 2209. B.F.Molino, J.Cusmano, D.R.Mootoo, R.Faqhih, and B-Fraser-Reid,

.

.

Y-Ichikawa, M.Isobe, H.Masaki, 4759.

?

.

15 Aldosuloses, Dialdoses, and Diuloses 1

Aldosuloses

The enolate of methyl 4 , 6 - g - b e n z y l i d e n e - 3 - d e o x y - 3 - ~ - m e t h y l - ~ - D ~arabino-hexopyranosid-2-ulose (1)

has been trapped by reaction at

oxygen to give (2) and at carbon to give (3) and submitted to 1 Robinson annulation to give (4) (Scheme 1).

Scheme 1

Two reports have appeared of the occurrence o f 6-D-ribo-hexopyranosid-3-ulose residues in plants: in cardenolide glycosides o f air dried (but not fresh) leaves o f two Cerbera s p e c i e s I L

and in

iridoid glycosides from Penstemon confertus leaves. Modified 4 members of the series ( 5 ) and a compound containing the unit ( 6 ) 5 which are, likewise, plant products have also been described.

Also in the hexos-3-ulose series the ketone (7) has been made easily from the D-galacto-alcohol by use of P C C on alumina under reflux in benzene,6 the D-ribo-compounds ( 8 ) were obtained by treatment of the corresponding 3-nitro-D-allo-2,3-epoxide

with

nucleophiles (epimerization occurring at C-2) ,7 and reduction with zinc borohydride of the enolone (9) gave the 3-ulose derivative (10). The isomer (11) was made in parallel fashion.

8

151

15: Aldosuloses, Dialdoses, and Diuloses

Diketones, e.y.,

(121, obtained from D-mannose-containing

compounds, on reduction have given access to both l,2-'

and 1 , 3 -

10

linked D-mannosyl-D-talose and D-talosyl-D-talose disaccharides. Photolysis of the D-fructose 6-pyruvate ( 1 3 ) gave the unusual D-lyxo-hexos-5-ulose derivative

I1

(141,

and the tricarbonyl

compound (15) was made by anodic oxidation of lI2-g-isopropylideneThe 3 - a c e t a m i d o - D - x y l o - h e x - 5 -

a-D-glucofuranose in high yield.12

ulose derivative (16) has been synthesized from 1,2:5,6-di-O--

isopropylidene-a-D-glucose by way of a 5-alkene.

$ H 20 B DPS

$ H 20 BPPS

13

Mec OCO 2 c ~ 2

CHO

OH

OH (14)

OH

Me

2

A

Dialdoses

review has been published on the irradiation of hexoses in

methanol in the presence of titanium tetrachloride which results in pentodialdoses by C-5, C-6 cleavage.

14

More specifically, 1,2-0-

isopropylidene-a-D-glucose 6-pyruvate on photolysis in benzene 11 (17). gives the dialdose Specifically C-6 deuterated D-galactopyranose derivatives have been shown by n.m.r.

to have the gt preferred rotamer state about

152 C-5

Carbohydrate Chernistry

-

C-6, and the methyl 6-D-pyranosides were used to show that a

D-galactose oxidase gives the dialdose glycoside mainly by p r o - S 15 hydrogen specific oxidation. Homologation by highly stereoselective addition of Z-trimethylsilylthiazole (a formyl anion equivalent) has been effected by a highly stereoselective process as indicated in Scheme 2 .

c HO

Di-c-isopropylidene-D-galactose

1,2:3,4-

/=/

was treated similarly and the

product (18) was again treated to give ( 1 9 ) , but with reduced 16 diastereoselectivity.

3

Diuloses

Oxidation of 1 , 2 : 5 , 6 - d i - ~ - i s o p r o p y l i d e n e - D - m a n n i t o l

gave the diulose

which on hydrolysis gave the crystalline ( 2 1 ) I and this 17 afforded derivatives as shown in Scheme 3. (201,

15: Aldosuloses, Dialdoses, and Diuloses

153

Re fe rence s

16

R.V.Bonnert and P.R.Jenkins, J. Chem. SOC., Chem. Commun., 1987, 6. T-Yamauchi,F.Abe, and A.S.C.Wan, Chem. Pharm., Bull., 1987, 35, 4813. B.Gering, P.Junior, and M.Wicht1, Phytochemistry, 1987, 26, 3011. D.Takaoka, Y.11, H.Nozaki, M.Nakayama, T.Tada, and S.Kooda, Tennen Yuki Kagobutsu Toronkai Koen Yoshishu, 1986, 28, 240 (Chem. Abstr., 1987, 107, 237 145). P.S.Steyn, F.R.Van Heerden, and R.Vleggaar, S. Afr. J. Chem., 1986, 2, 143 (Chem. Abstr. , 1987, 107, 115 869). W.Ma and F.W.Lichtenthaler, Yiyao Gongye, 1987, 2, 67 (Chem. Abstr., 1987, 107, 217 948). T.Nakagawa, T.Sakakibara, S.Kumazawa, Y.Hoshijima, and R.Sudoh, Carbohydr. Res., 1987, 163,227. G-Oremek, U.B.Sei€fert, and L.Prajer-Janczewska, Chem.-Ztg., 1985, 109, 390 (Chem. Abstr., 1987, 106, 18 949). R.K.Jain, R.Dubey, S.A.Abbas, and K.L.Matta, Carbohydr. Res., 1987, 161,31. R.Dubey, R.K.Jain, S.A.Abbas, and K.L.Matta, Carbohydr. Res., 1987, 165, 189. L.Den Drijver, C.W.Holzapfe1, M.S.Van Dyk, and G.J.Kruger, Carbohydr. Res., 1987, 161,65. P.A.Garcia, R.Velasco, and F.Barba, Chem. Ser., 1986, 26, 579 (Chem. Abstr., 1987, 106, 109 910). M.K.Gurjar and V.J.Pati1, Indian J. Chem., Sect. B, 1986, 25,1017 (Chem. Abstr., 1987, 107, 134 563). S-Ichikawa and T.Sato, Yuki Gosei Kagaku Kyokaishi, 1986, 44, 1047 (Chem. Abstr., 1987, 107, 23 5 8 0 ) . H.Ohrui, Y.Nishida, H.Higuchi, H.Hori, and H.Meguro, Can. J. Chem., 1987, 65, 1145. A.Dondoni, G.Fantin, M.Fogagnolo, and A.Medici, Chem. Pharm. Bull., 1987, 43,

17

J.Kuszmann, G-Medgyes, and G.Jerkovics, Carbohydr. Res., 1987, 164,459.

1 2

3 4

5 6

7 8

9 10 11 12

13 14 15

16 Sugar Acids and Lactones

1

General

A review has appeared on the analysis, structures, nomenclatures and reactions of a.cids derived from monosaccharides and polysaccharides?

2

Aldonic Acids

6-Deoxy-D-mannono-l,4-lactone has been found for the first time as a 2 plant product. Configurational and conformational conclusions have been drawn from the ‘H n.m.r. spectra of aldonates and aldaratesY3 and the solution conformations of aldono-l,4-lactones enriched with I3C at C-1 have been determined using ’H-’H, l 3 C - I H and l 3 C - l 3 C coupling constants. More specifically , the conformational solution equilibrium of 2,4,6-tri-~-benzoyl-3-deoxy-D-arabino-hexono-1,5lactone has been described following ’H n.m.r. analysis.5 The non-enzymic oxidation of D-glucose ( t o D-gluconic acid) and of related polyhydroxyaldehydes by pyrroloquinoline quinone, the coenzyme PQQ of several oxidoreductases, e.g., glucose dehydrogenases, has been shown to involve the 1,2-enediolateY and the differences in substrate reactivity correlate mainly with the equilibrium concentrat,ions of the acyclic modifications from which the enediol6 ate is produced. 2-Deoxyaldonic acids result in good yield from the treatment of aldose 2-sulphonates with aqueous lead (11) hydroxide under nitrogen. Related conversion in excellent yield of 1,6-di-O--tosyl-Dfructose into 2-deoxy-D-arabino-hexonic acid on reaction with this 8 lead derivative in chloroform is much more remarkable. Studies carried out on aldonic acids relate to the C-2 epimerization of the pentonic acids in aqueous alkali,’ the increased abilities of aldonates to coordinate calcium ion in alkaline solution when in the presence of borate ions,” and the thermal behaviour of 2-benzylamino-2-deoxyheptonic acids in air and in nitrogen. 11

155

16: Sugar Acids and Lactones

Several studies have concerned 2,3-unsatursted aldonolactones. Oxidation of glycoside (1) with hydrogen peroxide and catalytic molybdenum trioxide gave mainly the unstable a-hydroperoxide (2) 12 which readily affords the lactone (3).

0

(1 )

( 3)

(2)

More specifically, an L-threo-hexonolactone derivative was made by a specific C-5 inversion procedure as indicated in Scheme l . I 3 Two

0 .- L

Bn0

-

ReqMs

L,

CCOZH -=+ 0 CCI2OAU

:)=o

--L

CHZOAU. -0

BnO

OEt

-

BnO

-

MCPBA-BF3 Ef20, U, L L O H - H ~ O,'u, Ph3P-DEAD

Scheme 1

approaches, one from D-ribono-1,4-la~tone'~and one by way of a Wittig procedure,15 to the crystalline synthon (5)-5-hydroxymethyl-2 16 (5H)-furanone are illustrated in Scheme 2. C02Mc

CHZOH

';"2. OH

L

L,

HBr-HOAc,

v

CH2OY

.Z!L

1;-"2. -

CHO

px c-p x

CH

2-

OAc

OH

R cqedS

pp

CCI,OAc

LL.,

Na.tiSO,(aq,)

,uH ,C L - H ~ O - M ~ O H , IPhjP=CHCOZMe,v, V,

H'

Scheme 2

A considerable number of aldonic acid derivatives have been reported. Acyclic derivatives are the substituted free acids (4) (Scheme 3 ) 1 7 and the pyrazoles (5) (Scheme , ) . I 8 The s p i r o -

Carbohydrate Chemistry

156

R=

C H 2 OAC ReageAtts :

compounds (6) and ( 7 ) have been prepared as indicated in Scheme 5, the latter having the stereochemistry at the spiro-centre of a

unit of the orthosomycins . l9 The diaza-spiro compound ( 8) , which is related t o the nucleosides, was made as shown in Scheme 6.20

m:x'."..

CN

ONC N

AcO

K

H

2

--L Ac 0

OAc OAC

O A c OAc

Reagents:

i, D D Q - M e O H

Scheme

6

(8)

The anhydro-octonic acid derivative ( 9 ) and several derivatives made by modification of the ester group have been synthesized as CMP-KDO 21 synthetase inhibitors. In the 1,4-lactone series compounds (lo), the plant products ( - ) litsenolides, were made by Wittig procedures from a 2-uloside derivative,22 and the aminolactone (11) was derived f r o m 5,6-0isopropylidene-D-mannono-l,4-lactone as a precursor of trihydroxy-

157

16: Sugar Acids and Lactones n o r l e u c i n e (12). 23

The c h e m i s t r y o u t l i n e d i n Scheme 7 i l l u s t r a t e s 24

a n o v e l and u s e f u l e n t r y i n t o t h e o p t i c a l l y pur e c y c l o p e n t a n e s .

3 A I 3 C n.m.r.

S a c c h a r i n i c Acids s t u d y h a s b e e n c a r r i e d o u t on t h e a l k a l i n e d e g r a d a t i o n

p r o d u c t s o f m o n o s a c c h a r i d e s ; the a c i d i c p r o d u c t s w i t h up t o s i x c a r b o n a t o m s were r e a d i l y i d e n t i f i e d . d u r i n g t h e work. 2 5

[ l-13C1-D-Glucose

was u s e d

The main p r o d u c t s o f n i t r i c a c i d o x i d a t i o n o f g l u c o i s o s a c c h a r i n i c a c i d l a a t o n e ( 1 3 ) were f o u n d by g . 1 . c . - m . s .

after trimethyl-

s i l g l a t i o n t o be t h e a c i d s ( 1 4 ) and ( 1 5 ) and t h e i r r e s p e c t i v e l a c t o n e s (16) a n d ( 1 7 ) . 2 6

The same a u t h o r h a s f o u n d t h a t D,L-

x y l o i s o s a c c h a r i n i c a c i d Lactone ( 1 8 ) r e a r r a n g e s i n aqueous a c i d m a i n l y t o t h e tetrahydrofurancarboxylic a c i d (19).27

Go OH CH2OH

OH

('7)

D-Erythro-pentulose 1,5-diphosphate ( 2 0 ) with a l k a l i g i v e s t h e s a c c h a r i n i c a c i d monophosphate ( 2 1 1 , a p r o c e s s s u g g e s t e d t o p a r a l l e l t h a t occurring during t h e incorporation of pentose chains i n t o t h e base u n i t of r i b o f l a v i n .

I t was p r o p o s e d t h a t d e c a r b o x y l -

a t i o n of a compound s u c h as (21) p r o v i d e s t h e f o u r c a r b o n atoms r e q u i r e d . 28

158

Carbohydrate Chemistry

OH

Scheme 8

4

Ulosonic Acids

A s y n t h e s i s o f a r a c e m i c 3-deoxy-arabino-hept-2-ulosonate

derivative

i s o u t l i n e d i n Scheme 9,29 a n d t h a t o f a ~-L-gluco-hept-2-ulosonic

a c i d e s t e r i n Scheme 1 0 , t h e s t a r t i n g m a t e r i a l h a v i n g b e e n o b t a i n e d 3 T r e a t m e n t o f a 2-deoxy-2-fluoro-D-glucose by a W i t t i g p r o c e d u r e . ' and -D-mannose 6 - p h o s p h a t e s w i t h 3 - d e h g d r o q u i n a t e s y n t h e t a s e from

Reogcd: L ,

I

MCFBA

Scheme 10

R'

E . c o l i ( a n enzyme o f t h e s h i k i m i c a c i d p a t h w a y ) g a v e t h e h e p t - 2 u l o s o n i c a c i d s ( 2 2 ) a n d (231, r e s p e c t i v e l y , and t h e s e were t e s t e d as b i - o s y n t h e t i c p r e c u r s o r s o f 6 - f l u o r o s h i k i m i c a c i d d e r i v a t i v e s . 31 A new s y n t h e s i s o f 3-deoxy-D-manno-oct-2-ulosonic a c i d ( K D O ) has b e e n d e s c r i b e d (Scheme 11).32 T r e a t m e n t o f t h e p r o d u c t w i t h d i l u t e

Scheme 11

159

16: Sugar Acids and Lactones

acid gives mixed compounds from which the furanoid. 2,7-anhydride (24) and the furan (25) have been isolated.33 Acetylation of the

ammonium salt of KDO with acetic anhydride in the presence of sodium acetate gave mainly t h e a-penta-acetate, but s o w amounts of the lactone tetraester (26) were also formed. The small lactone system was formally obtained by the procesT indicated in Scheme 12. 34

L,U

L, 6 u Z S n 0 ; LC, BnBr

Scheme 12

Some C-glycoside derivatives of KDO have been prepared as indicated in Scheme 13. Compound (27) was characterized by x-ray CH~OAC

z )

~zM.

Reageht6

L, H l - P d / C

__3 L -uL

' A c o ~ M c

,&, MeO- ,u,

Lv'v

Me2W-Ht,

LV,

:KOzMe

R=

CN,COMe,etc

L O A , V, R X

S c h e m e 13

diffraction as a reference for determining anomeric configuration.35

The phosnhonate analogue of cytidine 5 0-monophospho-3-deoxy-D-mannooct-2-ulosonic acid has been synthesized as illustrated in Scheme 14,36 and "azacyclic-2-deoxy-KDO" was produced from KDO as shown in Scheme 15; both anomers were p o o r inhibitors of CMP-KDO synthetase. 37

Carbohydrate Chemistry

160

In the area of nonulosonic acids, three acetylated 2,3-unsaturated neuraminic acid derivatives have been isolated from urine or from submandibular glands of mammals. 38 A synthesis of N-acetylneuraminic acid (28) from E-acetyl-D-glucosamine is illustrated in Scheme 16,39 and 3-deoxy-~-glycero-D-galacto-nonulosonic acid ( 2 9 ) ,

which occurs naturally in a trout glycoprotein, has been made by condensation of D-mannose with pyruvic acid in the presence of immobilized acylneuraminate pyruvate lyase. D-Lyxose and 2-deoxyR'=OH, R'=CH~OH R'=OH, R2= H

R'=H OH

,R ~ = C H ~ O H

16: Sugar Acids and Lactones

161

.

D-arabino-hexose similarly gave ( 30) and (31) 40 From the relevant 41 2,3-ene the glycosyl donors (32), (33) and (34) have been prepaed, and the last of these gives B-glycosides, including disaccharides linked via primary and secondary positions, in the presence of trimethylsilyl triflate.42 On the other hand, a-glycosides were formed from 3-hydroxy 6-glycosyl halide analogues, the hydroxy group

Ac H NF; y

.p:

CH20Ac

OAc

Br

CO, M e

CO2 Me

C 0 2 Me

3

CH20H

3

Br

OCH2CHO

OH

(331

(32)

A c H N T oOH )co2H

($

(34)

(35)

being removable after glycoside formation.43 The a-glycoside (35), produced from the allyl analogue, was made f o r coupling to proteins as immunogenic neoglycoproteins, and the allyl glycoside copolymerized with acrylamide gave a water soluble polymer with useful serological properties.44 Various 7- and 8-0x0-derivatives of N-acetylneuraminic acid have been synthesized by specific methods,45 -

and 7- and 8-epimers of the 2,3-unsaturated analogue have been reported.46 The 6-thio compound (36) has been prepared from (37) by use of oxalylacetic acid,47 and N-acetylneuraminic acid gave (38) in 70% yield on treatment with benzyl, allyl or methyl halides in the

OH ( 37)

presence of cesium carbonate in DMF.

5

48

Uronic Acids

S itosterol 3-~-a-D-xyluronofuranoside, the first natural product recognized as containing this carbohydrate unit, has been isolated from a plant source.49 Treatment of a-D-galactopyranuronic acid with acetic anhydride and (diethylamino) pyridine gave the alkene ( 3 9 ) in high yield; heating in acetic anhydride together with acetic acid led to the pyranone (40).50 Elimination reactions were a l s o used to obtain the

162

Carbohydrate Chemistry

phenyl glycoside (41) and its B-anomer which were required for the examination of a glycosiduronase.51

"_;-. 0

(-J

CH ( O A C ) ~

0A c

OAc

-

A

c

0

b

*

OPh

OAc

OH

o+

52 Two conformational investigations - one a force-field study and the other a high field n.m.r. study53 - have been carried out on the a-idopyranuronic acid ring in connection with polysaccharide research. In the latter work disaccharide derivatives having the acid linked to D-mannose were prepared, and sulnhation was found to influence the adopted conformations appreciablv. In both studies the 'C1, 'Cq and 2S conformations were found to be significant. The deacylation of compounds such as the epimers (42) is difficult chemically, but can be achieved by selective enzymes; the D-gluco-compound was hvdrolysed with an As ergillus enzyme, and the L-ido-isomer by porcine pancreatic lipase. Several derivatives, including the ethyl ester and the 3-0dichlorophosphoryl acid chloride, of 1,2-0-cyclohexylidene-a-Dxylofuranuronic acid have been reported. " 3,5-Anhydrides of 1,2-~-isopropylidene-a-D-glucironic and -@-L-iduronic acid derivatives are described in Chapter 5. D-Glucuronolactone has been used in the preparation of several aminoacids related to D-glucuronic acid having nitrogen as the ring

--k----

hetero-atom (Chapter 24), and some octuronic acid derivatives are noted in Chapter 20.

6

Ascorbic Acids

A theoretical ,ginitio MO study of the oxidation of L-ascorbic acid to dehydroascorbic acid has been reported,56 and several further practical investigations have been described as follows: the Cu2+

catalysed reaction over a range of pH values,57 the related reaction using polyamine chelates of the metal ion,58 the Ru3+ - EDTA catalysed oxidation with hydrogen peroxide5' and the related oxygen oxidation.60 An essay has appeared on the existence of an equilibrium between ascorbic and dehydroascorbic acids.6OA Alkaline degradation of L-ascorbic acid affords over 50 products of which 32 have been identified as carboxylic acids which bear a

163

16: Sugar Acids and Lactones

61

relationship to human urinary organic acids.

Evidence f r o m the st,udy o f the complexing between vitamin C and cobalt-ammine cations suggests the ecid binds monodentally through 0-3 in [Co(NH3)? ascorbateI2+ and bidentally via 0-1 and 0-4 in 2+ 62 [ C O ( N H ~ )ascorbatel ~ . The product o f treatment of L-ascorbic acid with butenone is shown in Scheme 17; it reacts with ethanol and trimerizes as

S c h e m e 17

indicated. The trimeric product was characterized by x-ray diffraction analysis.63 Related work led to syntheses of the marine algal metabolite delesserine ( 4 3 ) and leucodrin (44) a phenolic 64 constituent of proteaceae (Scheme 18). CH20H

OH

A

COH

Q

+

0

+

+ O

>

:

y HO

OH OH

S c h e m e 18

The positive and negative ion laser-desorption Fourier transform mass spectra o f ascorbic and isoascorbic acid have been reported.65 See Chapter 15 for the electrochemical synthesis of 1,2-g-isopropylidene-D-xylo-5-hexulofuranurono-6,3-lactone.

164

Carbohydrate Chemistry

7

Aldaric Acids

The electrocatalytic oxidation of D-gluconic acid at a ubiquinonemixed carbon paste electrode with an immobilized layer of D-gluconate 66 dehydrogenase has been described. The aminolysis of diethyl xylarate proceeds as shown in Scheme

(19).67 CO,Et HO {OHOH

-&

C02Et

&age,&:

b0Ho{;l oeco CONHR

GO2 Et

i l RNHz

_j,

OH

CONHR

H0{OH OH

-----f

C02EL

Scheme

OH

CONHR

19

The 4,8-anhydroundecaldaric acid derivative (46) has been prepared as indicated in Scheme 20. The epimeric mononitriles (45)

were converted into the D-gluco-compound by a second photobromination procedure which can be rationalized in terms of the conformation of the intermediate C-5 radical.68 Condensation between tetra-0-acetyl-D-galactaric acid dichloride and anthranilic acid gave tne diamide (47) and thence with acetic

anhydride compound (48) and further with aniline and phosphorus trichloride the quinazolone (49).69

165

16: Sugar Acids and Lactanes

Refereqces 1 2 3

4 5 6 7 8

A.Pekarovicova, M.Kosik, L.Repazova, J.Polonsky, A.Blazej, and J.Pearovic, Chem. Listy., 1986, 80, 821 (Chem. Abstr., 1987, 106, 214 202). L.Opieta1, M.Sovova, V.Hanus, and F.Tureaek, Pharmazie, 9986, 41, 605 (Chem. Abstr. , 1987, 106,47 192) M.Van Duin, J.A.Peters, A.P.G.Kieboom, and H.Van Bekkum, Map. Reson. Chem., 1986, 24, 832 (Chem. Abstr., 1987, 107,59 379). T.Angelotti, M.Krisko, T.O'Conner, and A.S.Seriann5, J. Am. Chem. Soc., 1987, 109, 4464. C.R.Nelson, Carbohydr. Res., 1987, 163,275. S.Itoh, M.Mure, and Y.Ohshiro, J. Chem. SOC., Chem. Commun., 1987, 1580. R.A.Gakhokidze and N.N.Sidamonidze, Zh. Obshch. Khim., 1986, 56, 487 (Chem. Abstr. , 1987, 106, 102 621) . R.A.Gakhokidzexd N.N.Sidamonidze, Zh. Org. a i m . , 1986, 2, 876 (Chem. Abstr., 1987, 106, 67 604). M.Kalman, J,Sokolowski, J.Szafranek, and H.L&nberg, J. Carbohydr. Chem., 1987, 6 , 587. N.Vap Duin, J.A.Peters, A.P.G.Kieboom, and H.Van Bekkum, Carbohydr. Res., 1987, 162, 65. A.B.Garcia, E.R.Galan, J.A.S.Blazquez, and C.V.Calahorro, J. Therm. Anal., 4986, 2, 241 (Chpm. Abstr. , 198,7, 106,18 972). M.Chmielewski, J.Jurczak, and S.Maciejewski, Carbohydr. Res., 1987, 165, 111. S.Salverde, S.Garcia-Ochoa, and M.Martin-Lomas, J. Chem. Soe., Chem. Commun., 1987, 1714. J.A.J.M.Vekemans, G.A.M.Franken, G.J.F.Chittenden, and E.F.Gode€roi, Tetrahedron Lett., 1987, 28, 2299. B.pafele and V.;rager, Liebigs Anp. Chem. , 1987, 85. A.G.M.Barrett and D-Dhanak,Tetrahedron Lett., 19q7, 2, 3327. U.Klein, K.Mohrs, H.Wild, and W.Steglich, Liebigs Ann. Chem., 1987, 485. J.M.Beau, G.Jaurand, J.Esnault, and P.Sinai;, Tetrahedron Lett., 1987, 28, 1105. J.P.Ferris and B.Devadas, J. Org. Chem., 1987, 52, 2355. K-Luthman,A-Claesson, A.M.Jawsen, and B.P.Prin9, Carbohydr. Res., 1987, 166, 233. =.Wood and G.M.Watson, J. Chem. SOC., Perkin Trans. I, 1987, 2681, J.A.J.M.Vekemans, R.G.M.de Bruyn, R.C.H.M.Caris, A.J.P.M.Kokx, J.J.H.G. Konigs, E.F.Godefroi, and G.J.F.Chittenden, J. Org. Chem,, 1987, 52, 1093. D.R.Borcherding, S.A.Scholtz, and R.T.Borchardt, J. Org. Chem., 1987, 52, 5457. J.M.de Bruijn, F.Touwslager, A.P.G.Kieboom, and H.Van Bekkum, Starch/Staerke, 1987, 39, 49 (Chem. Abstr., 1987, 107, 23 595). R.Al&, Carbohydr. Res., 1987, 161, 156. R.Al&, Acta Chem. Scand., Ser.B, 1987, 41, 76. D.H.G.Crout and J.A.Hadfield, J. Chem. SOC., Chem. Commun., 1987, 742. R.R.Schmidt , W .Frick, B .Haag-Zeino, and S .Apparao , Tetrahedron Lett. , I987, 2 4 , 4045. A.Saroli and A.Poutheau, Tetrahedron Lett., 1987, 28, 5501. !?.be Marechal, C.Froussios, and R.Azerad, Biochimie, 1986, 68, 1211 (Chem. AbStr,, 1987, 106,46 304). M.Imoto, S.Kusimoto, and T.Shiba, Tetrahedron Lett., 1987, 28, 6235. P.A.McNicholas, M.Batley, and J.W.Redmondj 'Carbohydr. Res., 1987, 165,17. D.Charon, F.-I.Auzanneau, C.M&ienne, and L.Szab6, Tetrahedron Lett. , 1987, 28, 1393. K.Luthman, M.Orbe, T.Waglund, and A.Claesson, J. Org. Chem., 1987, 52, 3777. D.W.Norbeck, J.B.Kramer, and P.A.Sartey, J. Orq. Chem., 1987, 52, 2174. D.W.Norbeck and J.B.Kramer, Tetrahedron Lett. , i987, 28, 773. A,K.Shukla, C.Schroder, U.N6hle, and R.Schauer, Carbohydr. ReS., 1987, 168, 199. R.Julina, I.Muller, A.Vasella, and R-Wyler, Carbohydr. Res., 1987, 415. C.Aug6 and C.Gautheron, J. Chem. SOC., Chem. Commun., 1987, 859.

-

.

I

9

10

11 12 13 14 15 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36

37 38 39

40

-

166 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58

59 60

60A 61 62 63 64 65 66 67 68 69

Carbohydrate Chemistry K.Okamoto, T.Kondo, and T.Goto, Bull. Chem. SOC. Jpn., 1987, 60, 631. K.Okamoto, T.Kondo, and T.Goto, Bull. Chem. SOC. Jpn., 1987, 60, 637 K.Okamoto, T.Kondo, and T.Goto, Tetrahedron, 1987, 43, 5919. R.Roy, C.A.Laferri&e, A.Gamian, and H.J.Jennings, J. Carbohydr. Chem., 1987, 5, 161. E.Zbira1, S-Phadtare, and W.Schmid, Liebigs Ann. Chem., 1987, 39. E.Zbira1, H.H.Brandstetter, R.Christian, and R-Schauer, Liebigs Ann. Chem., 1987, 781. H.Mack and R.Brossmer, Tetrahedron Lett., 1987, 28, 191. K.Furuhata, S.Sato, K-Anazawa, M.Goto, H.Takayanagi, and H.Ogura, Chem. Pharm. Bull., 1987, 35, 3609. A.M.Iribarren and A.B.Pomilio, Phytochemistry, 1987, 5 , 857. K.Tajima, Noguchi Kenkyusho Jiho, 1985, 15 (Chem. Abstr., 1987, 107, 78 183) . N.Otatani and Z.Yosizawa, Carbohydr. Res., 1987, 159, 25. M.Ragazzi, D.R.Ferro, and A.Provasoli, J. Comput. Chem., 1986, L, 105 (Chem. Abstr., 1987, 106,176 778). P.N.Sanderson, T.N.Huckerby, and I.A.Nieduszynski, Biochem. J., 1987, 243, 175 (gem. Abstr., 1987, 106,196 704). R.Csuk and B. I.Gl&zer, Carbohydr. Res. , 1987, 168,C9. D.Miljkovi6, N.Vukojevi6, D.Mini6, P.Hadzi6, and G.Hajdukovi6, J. Carbohydr. Chem., 1987, 6, 501. Y.Abe, S.Okada, H.Horii, S.Taniguchi, and S.Yamabe, J. Chem. SOC., Perkin Trans.11, 1987, 715. G.Chen and Y.Pang, Yaoxue Xuebao, 1987, 22, 217 (Chem. Abstr., 1987, 107, 198 776). G.Chen and Y.Pang, Wuli Muaxue Xuebao, 1987, 3, 278 (Chem. Abstr., 1987, 107, 115 868). M.M.Taqui Khan and R.S.Shukla; J. Mol. Catal., 1987, 39, 139 (Chem. Abstr., 1987, 107, 59 383). M.M.T.Khan and R.S.Shukla, J. Mol. Catal., 1986, 37, 269 (Chem. Abstr., 1987, 107,40 244). H.W.Mueller, 2 . Naturforsch., C: Biosci., 1986, 41, 1145 (Chem. Abstr., 1987, 106, 120 172). K.Niemela, J. Chromatogr., 1987, 399, 235. H.A.Tajmir-Riahi, Biophys. Chem., 1986, 25, 37 (Chem. Abstr., 1987, 107, 237 183). R.Arnold, G.Fodor, C.George, and I.Karle, Can. J. Chem., 1987, 65, 131. A.J.Poss and R.K.Relter, Tetrahedron Lett., 1987, 2, 2555. P.Coad, R.A.Coad, C.L.C.Yang, and C.L.Wilkins, Org. Mass Spectrom., 1987, 22, 75 (Chem. Abstr., 1987, 107,78 187). T.Ikeda, K.Miki, F.Fushimi, and M.Senda, Agric. Biol. Chem., 1987, 2, 747. P.D.Hoagland, H.Pessen, and G.G.McDonald, J. Carbohydr. Chem., 1987, 5, 495. R.Blattner, R.J.Ferrier, and R.Renner, J. Chem. SOC., Chem. Comun., 1987, 1007. E.S.H.El Ashry, N.Rashed, and A.Mousaad, J. Carbohydr. Chem., 1987, 6, 599.

17 Inorganic Derivatives

1

Carbon-bonded P h o s p h o r u s D e r i v a t i v e s

The f i r s t s u g a r a n a l o g u e s w i t h a p h o s p h i n o t h i o y l g r o u p i n t h e r i n g h a v e b e e n d e s c r i b e d w i t h t h e s y n t h e s i s o f 5-deoxy-3-0-methyl-5-C[phenylphosphinothioyl~-a-a n d 6-D-xylopyranoses A glycosyl p h o s p h o n a t e (1) h a s b e e n p r e p a r e d a s o u t l i n e d i n Scheme 1, d u r i n g t h e s y n t h e s i s o f a l i p i d a n a l o g u e ( 2 ) . The same s t r a t e g y i n t h e 2 D - g a l a c t o s e r i e s gave a 1:l m i x t u r e o f t h e p h o s p h o n a t e anomers ( 3 ) .

.

CHzOAc

CH20H I

R e a g e n t s : b,

P(OMe)3- TMSOTF

- CH2ClZ Scheme 1

The p h o s p h o n a t e ( 4 ) has b e e n s y n t h e s i z e d by e m p l o y i n g a n Arbusov

r e a c t i o n on t h e 6-bromo d e r i v a t i v e ( 5 ) , l e a d i n g t o n u c l e o s i d e S y n t h e s i s o f t h e 2-deoxy-B-KDO a n a l o g u e d e r i v a t i v e s Of ( 4 ) .3 ( 6 ) h a s b e e n r e p ~ r t e d ,as ~ w e l l as a 5 ' - c y t o s i n e d e r i v a t i v e o f t h e CH20H

phosphonic a c i d ( 7 ) .

2

'

O t h e r Carbon-bonded

Derivatives

- c o n t a i n i n g r i b o f u r a n o s i d e s ( 8 ) have been and t h e s y n t h e s i s of t h e i s o l a t e d from e d i b l e brown g l y c e r i d e ( 9 ) h a s b e e n r e p o r t e d . * The c i r c u l a r d i c h r o i s m of some d i s e l e n i d e s , e . g . , (lo), a n d t h e d i t e l l u r i d e (11) h a s b e e n s t u d i e d .9

A number o f a r s e n i c

Carbohydrate Chemistry

168 Ye O=As--CH2~ Q c H ~ c H ( o H ) C H ~ R

he

(11) X =Te

(8) R = OSO3H,SOJH, 0 P o20C H C~H ( O H ) C H ~ O H O H OH

(9)R=OH

Further studies on the formation of glycosyl manganese complexes (Vo1.19, p.29-30, 161) has shown that both the yield and stereoselectivity of the reaction is affected by adding bromide ion to the 10 reaction mixture (Scheme 2). C;HZOBn

90%

08n

OB II ( p on$>

90:2

NoMn(CO)s - K D r (3 eq.) ; u,NaMn(CD),-

Reag&:L,

0c:p

BuICN6r ( 3 ~3

Scheme 2

The use of glycosyl lithium reagents f o r the synthesis of higher The sugars by reaction with aldehydes has been reviewed.” configurationally stable glycosyl llthium species ( 1 2 ) and (13) (derived from the corresponding stannanes) were used to synthesize 2-deoxy-C-glycosides by effecting a conjugate addition on cyclic or acyclic enones .12 Proton abstraction from the thioglycoside (14)

gave the corresponding glycosyl lithium species which trapped electrophilic reagents from the a-face to give C-1 alkylated or acylated derivatives (15). It was postulated that the a-lithium species was formed due to intramolecular bonding of Li with 0-4.1 3

3

Oxygen-bonded Derivatives

A chelate of phenyl 4,6-~-(5)-benzylidene-2,3-~-bis(diphenylphosphino)-@-D-glucopyranoside with rhodium (I) gives a stable highly active catalyst for the hydrogenation o f g-acyl-dehydro-a-amino acids yielding, in high enantiomeric excess, g-acyl-(S)-a-amino

1 7: Inorganic Derivatives

169

acids .I4 The reaction of diethyldithioacetals of some pentoses with tris(diethy1amino)phosphite afforded 2,3:4,5-di-g-cyclic amidophosphites, which on treatment with sulphur gave the corresponding amidothiophosphates . l5 Treating phosphorus derivatives of monosaccharides with the platinum compound Pt(ly5-cyclooctadiene)C1 2 16 yielded platinum complexes, e.g., (16).

The structures of borate esters of some polyhydroxy carboxylates 1 in water has been studied usingC'' and H n.m.r.17 Sucrose has been selectively acetylated using its per-diethylboryl ester and derived boronate esters . I 8 The introduction and removal of tertbutyldimethylsilyloxy groups using boron derivatives has been carried out. The diethylboronate ester of an alcohol was converted t,o a tert-butyldimethylsilyl ether under Lewis acid catalysed conditions. Desilylation back to the diethylboronate derivative was achieved using bis(diethylborony1)oxide and trimethylsilyltriflate .I9 Treatment of 2,3: 5 , 6 - d i - Q - e t h y l b o r a n e d i - y l - a - D - m a n n o furanosyl bromide with C7-16 n-alkanols and sodium triethylborate gave corresponding B-mannofuranosyl alkyl glycosides. 20 A review on organotin derivatives of sugars has appeared covering trialkyltin alkoxides, dialkyltin alkoxides and derivatives containing other types of tin-sugar links.21 Cross-linked metalcontaining networks have been shown to be formed through the condensation of organostannanes with sucrose. 22 The C-2 epimerization of aldoses by various metal complexes has been the object of a number of studies outlined in chapter 2 . The Cotton effects of bidentate complexes between [Mo2 (OAC)~] and some sugar diols has been studied. It is proposed that the absolute configurations of open chain vicinal diols of the threo - configuration and of vicinal primary - secondary diols can be determined in this way.23 In a study of the interaction between ca.lcium ions and fructose, the I.R. spectra of free B-D-fructose and its various calcium complexes were examined, and a correlation between the spectral changes and the co-ordination sites involved was established .24 The standard enthalpies of transfer of ribose and arabinose from water to aqueous solutions of various metal salts has allowed the equilibrium constants and free energies and entropies of the associations

170

Curbohydrute Chemistry

t o be

L-Arabinose

++

i n t e r a c t s w i t h Sr

a n d Ba++ s a l t s

i n a q u e o u s s o l u t i o n t o g i v e c o m p l e x e s o f t h e t y p e M(L-Ara)X2.4H20 26 which have b e e n i s o l a t e d a n d c h a r a c t e r i z e d s p e c t r o s c o p i c a l l y .

-

S i m i l a r l y uranium

a r a b i n o s e s o l i d complexes o f t h e t y p e

U 0 2 ( L - A r a ) X 2 . 2H20 h a v e b e e n c h a r a c t e r i z e d . 27

f3-D-Glucurono-y-

l a c t o n e f o r m s s o l i d complexes w i t h s i l v e r ( I ) s a l t s which h a v e b e e n c h a r a c t e r i z e d by F . T . 1 . R .

and X-ray

powder d i f f r a c t i o n . 2 8

Freshly

p r e c i p i t a t e d a l u m i n i u m hydi-oxide h a s b e e n complexed w i t h a number

o f s u g a r s i n h o t w a t e r t o g i v e n o n - i o n i c c o l l o i d a l c h e l a t e s , Tsi!-!ere s t a b i l i t y , p e r c e n t a g e a l u m i n i u m c o n t e n t and i s o e l e c t r i c p o i n t s w e r e d e t e r m i n e d . 29 The i n c r e a s e d a b i l i t i e s o f a number o f p o l y h y d r o x y c a r b o x y l a t e s t o co-ordinate

calcium i n aqueous a l k a l i n e s o l u t i o n i n t h e p r e s e n c e

of b o r a t e i o n s h a s been s t u d i e d . 3 0

An e . p . r .

and p o t e n t i o m e t r i c

s t u d y o f t h e c o m p l e x a t i o n o f c o p p e r i o n s by g a l a c t u r o n i c a c i d and galacturonans has i n d i c a t e d t h e stepwise formation of Cu(I1)-galactu r o n a t e complexes.

Weaker bonds were f o r m e d w i t h p o l y m e r s t h a n w i t h

monomers, s o t h e g r e a t e r a f f i n i t y o f C u ( I 1 ) for t h e p o l y m e r s i n due m a i n l y t o e n t r o p i c e f f e c t s . 31

M a g n e t i c s u s c e p t i b i l i t y a n d Mossbauer

e m i s s i o n measurements have been used t o s t u d y t h e l o c a l m o d i f i c a t i o n s appearing around t h e c o b a l t c a t i o n a f t e r t h e dehydration p h o s p h a t e 7H20 c o m p l e x . 3 2 A s t u d y o f

r e a c t i o n of t h e Co-5'-inosine t h e lH a n d I 3 C

-

n.m.r.

s p e c t r a o f m e t h y l 2-acetamido-2-deoxy-hexo-

pyrariosides i n t h e presence o f l a n t h a n i d e i o n s i s mentioned i n chapter 9.

References 1 2

3 4 5 6 7

8 9 10 11

12 13

H.Yamamoto, T.Hanaya, N.Shiqetoh, H-Kawamoto, and S.Inokawa, Chem. Lett., 1987, 2081. K.Briner and A.Vasella, Helv. Chim. Acta, 1987, 70, 1341. N.S.Padyukova, M.Y.Karpeisky, L.I.Kolobushkina, and S.N.Mikhailov, Tetrahedron Lett., 1987, 28, 3623. K.Luthman, A.Claesson, A.M.Janssen, and B.P.Prina, Carbohydr., 1987, 166, 233. D.W,Norbeck, J.B.Kramer, and P.A.Lartey, J. Orq. Chem., 1987, 52, 2174. Y.Shibata, M.Morita, and J.S.Edmonds, Agric. Biol. Chem., 1987, 51, 391. J.S.Edmonds, M.Morita. and Y-Shibata,J. Chem. SOC. Perkin Trans., I , 1987, 577. D.P.McAdam, A.M.A.Perera, and R.V.Stick, Aust. J. Chem., 1987, 40, 1901. M.Michalska and G.Snatzke, Liebigs Ann. Chem., 1987, 179. P.DeShong, G.A.Slouqh, and V.Elango, Carbohydr. R e s . , 1987, 171, 342. P.Sinay, Nato Asi. Ser., Ser. C, 1986, 178,171 (Chem. Abstr., 1987, 106, 5333). D.K.Hutchison and P.L.Fuchs, J. Am. Chem. SOC., 1987, 109,4930. S.Valverde, S.Garcia-Ochoa, and M-Martin-Lomas,J. Chem. S O C . , Chem. Commun. , 1987, 383.

17: Inorganic Derivatives 14 15 16 17 18 19 20 21 22

23

24 25 26 27 28 29 30 31 32

171

R.Selke and H.Pracejus, J. Mol. Catal., 1986, 37, 213 (Chem. Abstr., 1987, 107, 198 862). -

V.N.Nabiullin, E.T.Mukmenev, and B.A.Arbuzov, Zh. Org. Khim., 1986, 22, 2007 (Chem. Abstr., 1987, 107,59 336). E.E.Nifant’ev, E.V.Chechegoeva, and V.M.Zhelyaev, D o k l . mad. Nauk SSSR, 1986, 287, 874 (Chem. Abstr., 1987, 106, 120 151). M.Van Duin, J.A.Peters, A.P.G.Kieboom, and H.Van Bekkum, Recl. Trav. Chim. Pays-Bas, 1986, 105, 488 (Chem. Abstr., 1987, 107,59 381). K.M.Taba, R.KEster, and W.V.Dahlhoff, Liebigs Ann. Chern., 1987, 463. W.V.Dahlhoff and K.M.Taba, Synthesis, 1986, 561 (Chem. Abstr., 1987, 107, 23 585). W.V.Dahlhoff, Synthesis, 1987, 366 (Chem. Abstr., 1987, 107,237 153). A.Patel and R.C.Poller, Rev. Silicon, Germanium, Tin Lead Compd., 1985, -8, 263 (Chem. Abstr., 1987, 107,23 581). Y.Naoshima, C.E.Carraher, S.Hirono, T.S.Bekele, and P.D.Mykytiuk, Polym. Sci. Technol. (Plenum), 1986, 33, 53 (Chem. Abstr., 1987, 106, 120 161). A.Liptak, J.Frelek, G-Snatzke, and I.Vlahov, Carhohvdr. Res., 1987, 164, 149, H.A.Tajmir-Riahi, J. Inorq. Biochem., 1986, 27, 123 (Chem. Abstr., 1987, 106, 5339). A.Maestre Alvarez, N.More1-Desrosiers, and J.-P.More1, Can. J. Che-m., 1987, 65, 2656. H.A.Tajmir-Riahi, Biophys. Chem., 1986, 25, 271 (Chem. Abstr., 1987, 107, 40 208). H.A.Tajmir-Riahi, Monatsh. Chem., 1987, 118,245 (Chem. Abstr., 1987, 107, 154 610). H.A.Tajmir-Riahi, Inorg. Chim. Acta, 1987, 3, 93 (Chem. Abstr., 1987, 107, 189 439). I.H.Siddiqui, J.Jafri, and S.A.H.Zaidi, Pak. 3 . Sci. Ind. Res., 1986, 2, 95 (Chem. Abstr., 1987, 106,50 560). M.van Duin, J.A.Peters, A.P.G.Kieboom, and H.Van Bekkum, Carbohydr. Re$., 1987, 162, 65. P.Debongnie, M.Mestdagh, and M.Rinaudo, Carbohydr. Res., 1987, 170, 137. A.Labarta, A.Caubet, R.Rodriguez, E.Molins, J.Tejada, and V.Moreno, 2. Phye. Chem. (Munich), 1986, 149, 201 (Chem. Abstr., 1987, 106,63 167).

18 Alditols and Cyclitols 1 Alditols 1.1 Acyclic Aldito1s.- A new approach to the synthesis of optically pure polyhydroxylated compounds by i) the stereospecific reduction of chiral @-ketosulphoxides and ii) the stereospecific hydroxylation of chiral allylic p-hydroxysulphoxides has been described. Thus the unsaturated ester ( 1 ) gave the chiral sulphoxide (21, which was sequentially reduced, hydroxylated, and further reduced as outlined in Scheme 1 to give the 1,-arabinitol derivative (3) and hence penta0-acetyl-L-arabinitol in high yield; enantiomers are available by appropriate choice of the sulphoxide reagent. 1

Scheme 1

Further studies have been reported by Erimacombe's group on the synthesis of decitol derivatives; previously-described procedures have been used to prepare D-altro-D-galacto-decitol together with the L-altro- and C - and L-gluco- isomers derived from ?,2;3,4-di-c2 isopropylidene-D-galactopyranose. A comparison of routes to 4-pentenetriols using chiral-phase 6.c. showed that whereas D-ribonolactone gave the optically pure L-erythro isomer ( 4 ) , Grignard reaction of 2,3-?-isopropylideneD-glyceraldehyde gave a 62:38 mixture of the D-erythro and D-threo isomers ( 5 ) and ( 5 ) respectively, and Sharpless asymmetric epoxidation of divinylcarbinol gave either of the threo enantiomers with CH20SL Ph20ut

18: Alditols and Cyclitols

173

96% diastereoselectivity and 91-96% enantioselectivity. The derivative ( 7 ) of 3-deoxy-D-ribo-hexitol has been prepared from the 3-deoxy-hexose to confirm the configuration of an enantiomer obtained by routes from L-glutamic acid, D-ribonolactone or D-mannitol 4 during syntheses of the C(l)-C(13) segment of amphotericin R . A novel method for converting glycosides to acyclic derivatives involves the oxidative addition of the ring oxygen to a remote olefinic centre, with subsequent reductive cleavage, as illustrated in Scheme 2. 5 OBn

I

OBn

Me

ReageAtts: i, NBS-MeCN-NaHC03;ii,NaBH.+;Li', A c z 0 - O M A P ; w,Zn-EtOH-NH4CI

Scheme 2

Standard reactions have been used to convert aldehydo derivatives of D-ribose, D-xylose, and D-arabinose to the L-ribo-, L-xylo-, and D-lyxo- stereoisomers of octadecane-1,2,3,4-tetrols; the natural product guggultetrol-18 was shown to be the enantiomer of the L-xylo compound (8).6 (c H2 >,3M e

"{:: CH20H

OH

CHO

T +,.H CH20H

0

(9)

- t,ox LC,O

CH20H (10)

(3)

D-Mannitol has been used to prepare chiral glycerol derivatives. Nannitol 1,2;5,6-bis-acetonide 3-monobenzoate was labelled at C-4 with tritium by an oxidation-sodium borotritiide reduction procedure and then conventional 3-4 cleavage yielded the 1-tritiated glyceraldehyde, which was enzymatically reduced to the labelled glycerol (9); reduction of the unlabelled aldehyde with the enzyme (horseliver alcohol dehydrogenase) in presence of tritium-labelled cyclohexanol yielded the epimeric labelled glycerol (10). 7 Another paper describes the conversion of 1,3;4,6-di-g-acetalated D-mannitol to derivatives using and (~)-l-substituted-2-~-benzyl-glycerol conventional procedures. Fluorine-containing long-chain alkyl ethers of glycerol have been prepared from D-threitol, which were then converted to phosphorylcholine derivatives (see also Chapter 24). 9

Carbohydrate Chemistry

174

A study of the optimum parameters for the hydrogenation of D-glucose t o D-sorbitol has been reported. Physico-chemical properties of D-sorbitol have also been recorded. 11 1.2 Anhydro-1nositols.- A dianhydro-nonitol, a novel antitumour antibiotic, is mentioned in Chapter 19. Sharpless oxidation of (L1-2-butendiol 1-benzyl ether gave the D-threo oxiran (11 in 85% e.e. .I2 D-Elannitol has been used to

aoH

03

OH

OH

OH

OH

(13)

prepare 1,2;5,6-dianhydro derivatives (12) of mannitol and iditol, together with corresponding diaziridines, and hence enantiomerically pure oc-hydroxy and ff-amino-aldehydes and -acids.13 1,2;3,4;5,6Tri-oxiran derivatives of hexitols have also been reported from dianhydro-hex-3-enitol and hexatriene precursors using standard epoxidation procedures. 14 2,5-Anhydro derivatives (13) of 2-(D-allo and D-altro-pentitol-lyll-pyridines have been synthesized from 2,4;3,5-di-Q-benzylidene-Dribose and 2-silylated pyridine via the corresponding acyclic pentitols. 1 5 Di-anhydro-pentitols ( 1 4 ) and ( 1 5 ) have been prepared from 1,416 anhydro-5-chloro-5-deoxy-D-arabinitol and -D-xylitol respectively, and another paper has described a similar synthesis of the L-enantiomer of ( 1 5 ) together with oxetans of 2,5-anhydro-hexitols and the dioxetans ( 1 6 ) and ( 1 7 1 , 1 7 CH20Bn

(16)

(18)

(17)

Reaction of D-gluco- or D-galactosyl 1-acetates with trimethylsilylcyanide - b o r o n trifluoride etherate yielded ix- and ,6-glycosyl cyanides which were reduced to l-amino-2,6-anhydro-heptitols ( 1 8 ) using lithium aluminium hydride. 18 Procedures have been described for synthesizing 1,4;3,6-dianhydro-hexitols from D - g l u ~ i t o l2o ~ ~and D-mannitol ,I9 and for 1,4-anhydro-DL-xylitol from D-xyl itol ,21 under acid-catalysed 9

175

18: Alditols and Cyclitols

conditions. Acylation of 1,4;3,6-dianhydro-D-glucitol with acid anhydride in presence of lead oxide at room temperature gave mainly endo 0-5 ester, whereas using the anhydride alone at 12O-14O0C gave a mixture which, on distillation in presence of basic catalysts, yielded the more volatile exo 0-2 ester.22 A new synthesis of 1,4-anhydro-2-deoxy-D-erythro-pentitol has been described, and phosphotriester and phosphoramidite derivatives 23 were prepared and incorporated into synthetic DNA fragments. Synthetic immunomodulators combining lipid A and 1-deoxy-muramyl dipeptides have also been reported.24 F u l l details on the synthesis of a macrocyclic polyether incorporating 1,5-anhydro-D-glucitol have been p ~ b l i s h e d . ~ ~ ( s eVol. e 19, p.171). The contribution to the c.d. of pair interaction between acetyl groups in acetyl derivatives of 1,5-anhydro-alditols accounts for 26 the observed signal, and allows their stereochemistry tobe deduced. 1.3 Branched-Chain Aldito1s.- Doubly branched alditols ( 1 9 ) have been prepared (as sections of erythronolide B ) by cuprous cyanide catalysed cleavage of oxiran precursors (20) using methyl-lithium, 27 the precursors being readily available from D-glyceraldehyde.

CH20H

(19)

y

CH20H

b

e

OH

C H20 H (20)

OH

1 R

(21) R = Me

(22) R - t C H 2 0 H

R

0 O F F %

0

R

(23) R = Me, Et, Bn

2-~-Hydroxymethyl-2,3;5,6-di-O-isopropropylidene-D-mannofuranose has been converted conventionally to 6-deoxy-2-~-methyl-D-mannitol(21) and 2-C-hydroxymethyl-D-mannitol (22) as potentially sweet compounds but neither were sweeter than sucrose. 28 The related branched-chain mannitols (23) have also been prepared as potential asymmetric ligands for lithium aluminium hydride reagents, but these only show1,3,5-Trideoxyed low enantioselectivity in ketone 3,5-di-C-methyl-L-talitol, a chiron for the C(33)-C(37) segment of amphotericin B, has been prepared by standard reactions from 30 glucose (see also Chapters 14 and 24). 1.4 Amino-A1ditols.- Anti-selective reduction of acyclic cx-alkoxy and w,P-dialkoxy ketone oximes occurs with aluminium hydride reagents, L-threo-ketotetrose derivatives (24) giving L-xylitol analogues ( 2 5 ) preferentially (4:l ratio); chelation control was postulated. 31

reduction^.^^

Carbohydrate Chemistry

176

NH2

-.

2 0 M :.:$ :

2 u

Me0 C H 2 0

(25)

'"20Bn

(24) R = Me, Pr", p - M e O c61-14.

I-Amino-1-deoxy-alditol derivatives have been prepared conventionally from glucose and reducing oligosaccharides to provide linkage units to proteins32 and resins33 (see also Chapter 23); mixtures of reducing oligosaccharides can be easily separated on h.p.1.c. of their 1-amino-alditol derivatives.32 The stereochemistry of N-transacylation of 1,l-bis(acy1amido)-1deoxy-alditols using carboxylic anhydrides has been studied.34 The biological activity of some cyclic imino-alditol derivatives has provoked extensive interest in their chemistry. Fleet's group has published full details of syntheses of 1,4-dideoxy-1,4-imino-Dmannitol (see Vol. 18, p.168), 1,4-dideoxy-1,4-imino-D-lyxitol(Vol. 35 19, p.170) and swainsonine ( V n l . 18,p.253) from D-mannose, syntheses of 2,5-dideoxy-2,5-D-mannitol and 2,6-dideoxy-2,6-imino-Dmannofuranoside ( V o l . 19,p.169) from D - g l u ~ o s e ,and ~ ~ the conversion of the latter imino-mannoside into a range of 1,5-dideoxy-1,5-iminoalditols (26).37(Vo1.20,p.276, ref , 6 5 1 . They have also synthesized 1,4-dideoxy-1,4-imino-L-gulitol (27) and -D-lyxitol (28), together with the dihydroxy-proline (29) and 8-episwainsonine (30), from D-glucose via 3,6-dideoxy-3,6-imino-D-glucose(311 ,35 and have used

(26) R'= CHZOH or Co2H

R2=

H,OH,or N H A c

(27) R = CH2OH

(29)

(30)

(20)R = H

D-glucuronolactone to synthesize the epimeric 5-azido-sugars (32) and hence hydroxy-amino-acids which are proline or pipecolic acid derivatives, e.g., (33)-(35) .39p40(See also Chapter 24). OH

----+

N3&x

(32)

0%-

HO"

H

(33)

''lrco2H

t-&2w noT5:02H

HOCH2n<.

H

(3 4)

H

( 3 5 ) R-HorOH

Other workers have reported syntheses of 1,5-dideoxy-1,5-imino-D-

18: Alditols and Cyclitols

177

galactitol from D-galactose, with the key steps illustrated in Scheme 3 ,41 synthesis of the xylosaminitol derivative ( 3 6 ) from D-glucosamine in which the analogue of ( 3 7 ) was first ozonolysed and then reductively cyclized to form the ring,42 a multistep conversion of 1 -deoxy-nojir imycin to 2-acetamido-1 ,2 -dideoxy-nojir imycin,43 and a conversion of L-threitol to nojirimycin and 1-deoxy-nojirimycin as outlined in Scheme 4.44

m

.. u c .

t

BnO

Ho HO

BnO

BnO

0 Bn

OBn (major epmw)

(37) Reqents

Scheme

C H OH

CH

L!2+

O 1C H ~ O S L ~

1

CH 1 t -

?,

CHZOMOM

-MOM0

Swern o x u i d w n ,

~r,

"

0

1(

6

C H ~ O S L ~

J/

M01 O

'

L

CHO

U , P h 3 P = C H C 0 2 E t ,u, DlOAL,

S hwpLcss

@

-4

OH

Me0 C6HqCH 2 0 C O H N

Lv,

0{3N

CH2OH

HO

CH20MOM

Reag&

(36)

3

$

C02Et

1 CH20H

I

X= OAc or OCOCF,

Zn, B n N H 2 ,u, N a Q H 3 C N , M, k19X2

L.,

NHAc

ooH

HO

OH

owLdatwn

Scheme 4

Syntheses of 5-membered ring compounds have included an efficient four-step conversion of 1,3:4,6-di-~-benzylidene-D-mannitolto 2,5dideoxy-2,5-L-iditol (38), 4 5 the preparation of 1,4-dideoxy-l,4imino-D-arabinitol and -D-lyxitol (39) from non-carbohydrate precur46 sors (see also Chapter 24) and syntheses of 1,4-dideoxy-1,4-iminopentitols and hexitols (40) from a 1-amino-1-deoxy-D-mannitol precursor.46a HO cH2

H

R*

pH2°H

HO

OH HOCH2

(381

(39)

(40) R = H,CHaOH

1.5 Heterocyclic Derivatives.- Alditol-1-yl heterocycles are of interest as analogues or precursors of C-nucleosides. 1-Deoxy-1methylamino-D-hexitols treated with ketene dithioacetals produced

178

Carbohydrate Chemistry

corresponding heterocycles ( 4 1 ) .47 3,4 ,5,6 ,7-Penta-2-acetyl-1bromo-1-deoxy-D-galacto-heptulose has been used to construct a number of D-galacto-pentitol-1-yl heterocycles, including thiazole Sugar acid derivatives have been converted to 3substituted pyrazoles (42) in a five-stage reaction sequence.49

derivative^.^'

2" [=:R2 CHZOH

R1

RC02H

(41)

-

R

1 " G (42) H

(CCIOAC)~ ( O - G l c , I D -Gal)

R'= H,CN R2= C0*Et,NO2,CN

;==ISMe R-NYN CH20Ac

(43) R = H , P h

OAC

OAc

CH20Ac

1,2,4-Triazole derivatives (43) have been constructed from penta-)acetyl-E-[bis (methylthio)methylene] hexanamides using hydrazine and hydrazino derivatives. 50 D-Gluco- and D-Falacto-pentitol-1-yl derivatives of a number of heterocycles based on the 3-substituted indole skeleton have been prepared. 51 1.6 Miscellaneous Compounds.- 1,2-~-Isopropylidene-5-~-tosyl-w-Dxylofuranose has been used to prepare 1- and 5-deoxy-xylitol disulphide and sulphidederivatives in standard steps.52 Base treatment of cis,trans-1,2:5,6-di-)-~2-bromoethylidene~-~-mannitoland the corresponding cis,cis isomer gave the polycyclic derivatives ( 4 4 ) and (45) respectively, the products being unusually resistant to acid h y d r o l ~ s i s . ~Standard ~ reactions have been used to convert

( 44)

(45)

3,4-di-g-benzyl-D-mannitol to 2,3-2-protected D-glyceraldehyde derivatives using acetyl, silyl, or diisopropylmethylene acetal protecting groups. 54 2 Cyclitols

c-

2.1 1nositols.- Four new polyacylated derivatives of o r 1inositol have been isolated from aerial parts of klashallia t e n u i folia, in which up to four hydroxy groups carry acetyl or angeloyl groups.55 A new inositol glycoside , 2-g-B-L-arabinopyranosyl-myo56 inositol, has been isolated R S a m a j o r tea component.

179

18: Alditols and Cyclitols

A new synthesis of (kl-pinitol utilizes enzymatic hydrnxylation of benzene by Pseudomonas to give a cis-cyclohexadiene-l,2-diol which was then chemically oxidized in conventional steps to the 57 required inositol mono-methyl ether. A new monosaccharide to inositol conversion has been developed in which D-glucuronolactone was transformed into a 2,3,4,5-tetrasubstituted hexitol intermediate and then cyclized as illustrated for myo-inositol in Scheme 5. 58

I

CHO

OBn

OBn

Deuterium exchange on myo-inositol using deuterated Raney nickel in deuterium oxide yielded six other inositol isomers besides labelled myo-inositol; six of these labelled inositols could be separated by a combination of recrystallization and anion-exchange chromatogroup have recorded the conversion of myo-inositol g r a p h ~ . Gigg's ~~ to its 1,2,4- and 2,4,5-tri-?-benzyl ethers and its 1,2,3,4-tetra0-benzyl ether,60 its 1-L-1-)-methyl ether and its l-D-1,2,4,5,6penta-)-benzyl ether,61 and its 1,2:5,6- and 1,2:3,4-di-~-isopropylidene derivatives.62 Potassium superoxide in presence of crown-ether has been used as an oxygen nucleophile to invert myo- to scyllo-inositol.63 Standard procedures have been used to convert myo-inositol to 1-, 4 - , and 5deoxy-fluoro and 5-bromodeoxy and 5-chlorodeoxy analogues together with their epimers.64 2.2 Amino-1nositol.s.-An enantioselective synthesis of (-)-fortarnine in a multistep procedure from a chiral half-ester of cyclohex-4-ene~ - 1 , 2 - d i c a r b o x y l i cacid has been described,65 as has a conversion of D-glucose to valienamine, using the Ferrier rearrangement to form ap inosose ring, which was then reacted with cyanotrimethylsilane to introduce the branch carbon as a nitrile function; the intermediate (46) was then converted to valienamine (47) as outlined in Scheme 6.66 Valiolamine (48) together with the analogues (49) have been prepared from a chiral cyclenose precursor.67

A new synthesis of 2-deoxystreptamine ( 5 0 ) has been described, in which D-mannose was converted to the nitro-aldose (5l)(mannose numbering), cyclized to the corresponding epimeric nitro-cyclitols

Carbohydrate Chemistry

180

(46) R q & :

OH

i,DIBAL;ii, LAU;iii,BzCN-MeCN-NEt3;w, P P h , - D E A D ; v , ~ - i n e T ; v L , N a . - N H 3 ( L )

(47)

Scheme 6

(5')

(501

(52)

Scheme

7

(52), the appropriate epimer then giving 2-deoxystreptamine (Scheme .)7 68 Discogenic (liquid crystal) amido- and azido-derivatives of deoxy-scyllo-inositol have been described, in which a hexanoyl group is attached directly to the ring or through an amino nitrogen substituent.69 The acetalation of tetra-E-acylated neamine has been studied; acetone and cyclohexanone preferentially block the trans5,6-diol in the deoxystreptamine ring rather than the trans-3,4-diol in the neosamine ring; lead tetra-acetate oxidation then allows the 70 isolation of 2-deoxy-5,6-~-isopropylidene-streptamine. 2.3 Branched-Chain 1nositols.- A variety of strategies has been used to synthesize pseudo-sugars. The inosose made from D-glucose mentioned above (ref.66) has also been used to make 9-glucose and hydroxy-analogues (53) and (54) using known reactions.71 Ferrier ' s

kJOH -

OH

CH20H

B"@H

DnO

OBn

Or

0 Qn (53)

&Q ODn

(541

group has used the same approach to convert D-glucose to 9 - H - D glucose.72 The key intermediate (55), synthesized from D-glucose as outlined in Scheme 8, has been used to prepare v-d-L-altropyranose, ~+'-p-D-glucopyranose, q-2-amino-Z-deoxy-B-L-altropyranose, ~ - 2 - a m i n o - 2 - d e o x y - ~ - D - g l u c o p y r a n o s73 e , and JI-fi-L-allopyranoseand y-M-D-mannopyranose, 7 4 by addition to the enose function followed by cleavage of the C - 1 - C - 2 bond to generate the required hydroxymethyl group on the cyclohexane ring. D-Glucose has also been used to make the phosphonate ester (561, which after oxidation at C-2 and

181

18: Alditols and Cyclitols

C-6, underwent intramolecular Wittig condensation to the cyclenose (57), which could then be converted to cx and @ analogues of y-Dglucose and ~)-L-idose.~~ Full details of the synthesis of pseudo sugars using Knoevenagel condensation of aldehydo-sugars have been published (see V01.20,p.180).~~ A very similar method used a

5-deoxy-5-iodo-aldehydo-L-arabinose derivative to generate the cyclic dicarboxylate (58)(together with the anhydro compound (59)), leading to y-K-D-glucopyranose and 3/-fi-L-altropyranosevia the cyclohexene derivative (601, borane reduction in this case being non-stereoselective.7 7 Quebrachitol served as a source of the cyclenose (61) leading to the $b-M-D-glucosederivative (62); many COZMe

(J*"

c H (c o2M& QOBn

HO

OBn

(58)

MeoQo

QOBn 0 131-1

(59)

-

CH2OH

O6n (69

Me0QOH

OBn

(61)

CH20H

OBn

(62)

related compounds are described in this paper. 78 The pseudo-sugars were subsequently linked conventionally to methyl glucopyranoside derivatives to give H-1+4 and ct-1+6 linked p-disaccharides.79 Y-P-D- and -L-fructopyranose have been synthesized from optically active endo-adducts of furan and acrylic acid using methodology already applied in the racemic series (see Vo1.2O,p.181). 80 A synthesis of the ring skeleton of the alkaloid histrionicotoxin involves condensation of the lyxodialdose (63) with a 5-nitropentanol derivative followed by cyclization to the branched-chain nitrocyclitol (64)(see also Chapter 24) .81 Di-2-isopropylidene derivatives of (?)-y-cx-D-galactopyranose have been synthesized, the 1,2:3,4

Carbohydrate Chemistry

182

di-0-isopropylidene derivative then being used to prepare further h substituted derivatives including 1-6 linked q-disaccharides with 82 8-D-glucose, obtained as separable diastereoisomers. Treatment of 1,5- or 1,6-anhydro-sugars with LDA yields isomeric cyclopentanone or cyclohoxanone derivatives, e.p,., (65)-+(66); with butyllithium, alkylation leading to ltetose sugars also occurred, e.g., (67)(Scheme 9). 83

oyo

0

r0

O Y O Ph

Ph

(65)

Scheme

Ph

(66)

(67)

9

A new plant-growth regulator, streptol, isolated from an unidentified Streptomyces strain, is the shikimic acid analogue (68).84 A synthesis of DL-shikimic acid from a Diels-Alder adduct of furan and 85 . .. acrylic acid has been described, utilizing the intermediate (69).

0 nowo2M= NH2

C02Me

Ph

OH

(69)

Another paper has reported a multistep conversion of D-lyxose to methyl (-1-shikimate.86 Interest in carbocyclic analogues of nucleosides has led to syntheses of q-p-D-arabinofuranose from an aldehydo-D-xylose derivative via a Knoevenagel condensation with methyl malonate (see also ref.76 above 1 , 8 7 the carbocycl ic ribosylamine ( 7 0 1 from the racemic aminoacid ( 7 1 ) using an esterase to achieve asymmetric saponification and hence resolution,88 and another synthesis of this same analogue ( 7 0 ) from q-a-L-arabinofuranose using the cyclopentanone (72) to epimerize the hydroxymethyl group. 89 A novel carbocyclization enerating OH

Ph

2-2

P7-0

ODn

(73) X = O Bn,H

4

x

3

c101-1

(74) Y = H , O M e

OH

18: Alditols and Cyclitols

183

cyclopentanes from pyranose derivatives has been reported; Wittig olefination of the derivative (73) gave an alkene which on radical deoxygenation at C-5 gave the single product (74); by contrast-, the 00 4,6-di-c-benzyl analogue of (73) gave a mixture of stereoisorners. References to carbocyclic nucleosides are given in Chapter 20. 2.4 Inositol Phosphates.- There has been a surge of interest in these biologically interesting compounds. Gigg’s group has published papers on the synthesis of myo-inositol phosphates and thiophosphates using phosphite intermediates,91 the synthesis of ( 2 ) myo- inositol 4,5-bisphosphate,92 ( 2 1 -myo- inositol 1 ,4,5- tr isphosphate ,93994 and myo-inositol 1,4,5-trisphosphorothioate (751, a 95 novel analogue of the biologically active ‘second messenger’. Other groups have also reported syntheses of D- and L-myo-inositol 97 1,4,5-tr isphosphate,9 Q DL- and D-myo-inos itol 1 ,4,5-tr isphosphate, and DL-myo-inositol 1,3,4-trisphosphate,2,4,5-trisphosphate, and 1,3,4,5-tetrakisphosphate,98 D-myo-inositol 1,3,4,5-tetrakis100 p h ~ s p h a t e , ’and ~ DL-myo-inositol 2,4,5-trisphosphate. The myo-inositol orthoformate (76) underwent highly regio-selective mono-phosphorylation t o give the 4-phosphate derivative, and

fi H

HO

(76)

OH

conventional steps were used to prepare the 1,3-bisphosphate and 1 , 3 , 4 , 5 - t e t r a k i s p h 0 s p h a t e ; ~ the ~ ~ same group has also reported synthesis of racemic and resolved myo-inositol 1- and 4-phosphates from benzyl ether or cyclohexylidene myo-inositol precursors.102 The identities of inositol lY3,4-trisphosphateand 1,3,4,5-tetrakisphosphate have been confirmed using 1D and 2D multinuclear n.n.r. data, which showed that all phosphates occupy equatorial positions on the cyclohexane ring. 103 2.5 Miscellaneous Cyclito1s.- Racemic tetra- and penta-c-acetyl-snmyo-inositols have been resolved using diastereoisomeric orthoesters with mannose. 104 The effect of pH on calcium binding to phytic acid has been studied 105 A semi-empirical theory of optical activity incorporating high energy states of relevance to vacuum U.V. has been applied to cyclohexane polyols, giving moderately good correlation with experimental results.106

.

Carbohydrate Chemistry

184 References 1 2 3

4 5

10 11

12 13 14 15 16 17 18

19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38

39

m., m.=.,

G.Solladie, J.Hutt, and C.Frechou, Tetrahedron 1967, 28, 61. J.S.Brimacombe, R.Hanna, and A.K.M.S.Kabir, J . Perkin Trans. 1, 1987, 2421. B.Koppenhoefer, M.Walser, D.SchrOter, B.E-Iafele,and V.J’ager, Tetrahedron, 1987, 43, 2059. 1987, 2,1143. S.Hanessian, S.P.Sahoo, and M.Botta, Tetrahedron D.R.Mootoo, V.Date, and B.Fraser-Reid, 2. Chem. SOC., Chem. Commun., 1987, 1462. V.Kumar and S.Dev, Tetrahedron, 1987, 43, 5933. C.A.Townsend and S.Mao, J. Chem. SOC., Chem. Commun., 1987, 86. U.Peters, W.Bankova, and P.Welze1, Tetrahedron, 1987, 43, 3803. K.Fugita, S.Kobayashi, I.Kudo, K.Inoue, S.Nojima, M.Ohno, Y-Kobayashi, Y.Odagiri, and T.Taguchi, Chem. Pharm. B u l l . , 1987, 35, 647. D.R.Agzamkhodzhaeva, M.T.Ikramutdinova, S.T.Karimov, and M.F.Abidova, &&. Khim. Z&., 1986, 45 (Chem. Abstr., 1987, 107, 115 884). A.I.Gubareva, P,A,Gerasimov, and E.L.Rlokh, 2. Prikl. Khim. (Leningrad), 1986, 59, 865 (Chem. Abstr., 1987, 106,33408). J.Soulie, K.Lampilas, and J.Y.Lallemand, Tetrahedron, 1987, 43, 2701. Y.Le Merrer, A.Dureault, C.Greck, D.Micas-Languin, C.Gravier, and J.-C.Depezay, Heterocycles, 1987, 25, 541. P.Kol1, J.Kopf, J.O.Metzger, W.Schwarting, and M.Oelting, Liebigs Ann. Chem., 1987, 199. J.A.Galbis Perez, E.Roman Galan, M.Bueno Martincez, and A.Cert Ventula, Carbohydr. g . ,1987, 170, 240. 1986, A.Wisniewski, J.Gajdus, J.Sokolowski, and J.Szafranek, pol. J. E., 60, 515. P.Koll and M.Oelting, Liebigs 1987, 205. M.-T.Garcia Lgpez, F.G.De Las I-leras,and A.San Felix, J. Carbohydr. Chem., 1987, 6, 273. Z,Cekovic, J.Serb. Chem. SOC., 1986, 2, 205 (Chem. Abstr., 198?, 106,196709). S.Krauze, E.Gromadzinska, and J.Ojrzanowski, Acta Pol. Pharm., 1986, 43, 411 (Chem. Abstr., 1987, 106,214 245). N.Zhang, T.Jin, Z.Tian, and J.Song, Hebei Daxue Xuebao, Ziran Kexueban, 1986, 68 (Chem. Abstr., 1987, 106,67580). P.Stoss, P.Merrath, and G.SchlCter, Synthesis, 1987, 174. R.Eritja, P.A.Xalker, S.K.dandal1, M.F.Goodman, and B.E.Kaplan, Nucleosides Nucleotides, 1987, 6, 803. Y.Fujishima, K.Kigawa, Y.Ogawa, M.Kiso, A.Hasegawa, H-Ishida, and I.Azuma, Carbohydr. E.,1987, 167, 317. A.Hernandez, M.Alonso-Lopez, M.Martin-Lomas, C.Pascua1, and S.Penades, Tetrahedron, 1987, 43, 5457. P-Salvadori, C.Bertucci, D.Pini, and G.Zullino, Carbohydr. K.,1987, =,9. J.Mulzer, L.Autenrieth-Ansorge, H.Kirstein, T.Matsuoka, and W.MCnch, J . Org. Chem., 1987, 52, 3784. 1987, 169, 252. Z.B.Witczak and R.L.Whistler, Carbohydr. N.Baggett, R.J.Simmonds, and P.Stribblehil1, Carbohydr. &., 1987, 162, 153. D.Liang, A.D.Schuda, and B.Fraser-Reid, Carbohydr. 1987, 164,229. H.Iida, N.Yamazaki, and C.Kibayashi, J.Chem. S O C . , Chem. Commun., 1987, 746. E.Kallin, H,Loenn, and T.Norberg, Glycoconjugate J.,1986, 2, 311 (M. Abstr., 1987, 106, 152 486). S.Honda, S.Suzuki, and K.Kakehi, J. Chromatogr., 1987, 396, 93. R.A.Cadenas, I.Vacas, I.Pallares, and M.E.Gelpi, An. Asoc. Quim. Argent., 1986, 74, 251 (Chem. Abstr., 1987, 107, 23629). B.P.Bashya1, G.W.J.Fleet, M.J.Gough. and P.W.Smith, Tetrahedron, 1987, 43, 3083. G.W.J.Fleet and P.W.Smith, Tetrahedron, 1987, 43, 971. G.W.J.Fleet, L.E.Fellows, and P.FJ.Smith, Tetrahedron, 1987, 43, 979. G.N.Austin, P.D.Baird, G.W.J.Fleet, J.M.Peach, P.W.Smith, and D.J.Watkin, Tetrahedron, 1987, 43, 3095. B.P.Bashya1, H.-F.Chow, L.E.Fellows, and G.W. J. Fleet, Tetrahedron, 1987, 43,

w.,

&.

w.,

e., e.,

18: Alditols and Cyclitols

40 41 42 43 44 45 46 46a 47

48 49 50 51 52 53 54 55 56 57 58 59 60 61

62 63 64 65 66 67 68 69

70 71 72 73 74 75 76 77 78 79 80

185

415. B.P.Bashya1, H.-F.Chow, and G.W.J.Fleet, Tetrahedron, 1987, 43, 423. R.C.Bernatos, M.A.Pezzone, and B.Ganem, Carbohydr. 1987, 167, 305. R.C.Bernatos and B.Ganem, Carbohydr. &., 1987, 167, 312. H.Boshagen, F.R.Heiker, and A.M.Schuller, Carboh dr. Res., 1987, 164, 141. H.Iida, N.Yamazaki, and C.Kibayashi, J . Org. 1987, 52, 3337. T.K.M.Shing, J. Chem. S O C . , Chem. Commun., 1987, 262. N.Ikota and A.Hanaki, Chem. Pharm. Bull., 1987, 35, 2140. H.Setoi, H.Kayakiri, H.Takeno, and M.Hashimoto, Chem. Pharm. Bull., 1987, 35, 3995 A.Boerner, H.Kristen,K.Peseke, and M.Michalik, J . Prakt. Chem., 1986, 328, 21 (Chem. Abstr., 1987, 106,18948). K.Peseke, I.Farkas, and A.Kerber, Pharmazie, 1986, 41, 548 (Chem. Abstr., 1987.’ -107. 78192). , U.Klein, K.Mohrs, H.Wild, and W.Steglich, Liebigs Ann. Chem., 1987, 485. H.Kristen, I,Meerwald, and A.Eoerner, Pharmazie, 1986, 41, 551 (Chem. Abstr., 1987, 107,59390). M.J.Dihnez, J.Galh, A.Gbmez-Ssnchez, A.LGpez-Castro, and M.Rico., J . SOC., Perkin Trans. 1, 1987, 581. A.U.Rahman, J.R.Danie1, and R.L.Whistler, J. Chem. S O C . , 1986, 8,397 (Chem. Abstr., 1987, 107,97017). H.B.Sinclair, Carbohydr. E . ,1987, 165,23. J.Jurczak, T.Bauer, and M.Chmielewski, Carboh dr. Res., 1987, 164,493. W.Herz and M.Bruno, Phytochemistry, 1987, 6,’117571737. K.Sakata, H,Yamauchi, A.Yagi, and K.Ina, Agric. Biol. Chem., 1987, 2, S.V.Ley, F.Sternfeld, and S.Taylor, Tetrahedron g., 1987, 28, 225. Y.Watanabe, M.Mitane, and S.Ozski, Chem. Lett., 1987, 123. K.Sasaki, F.Balsa, and I.E.P.Taylor, Carbohydr. &., 1987, 166,171. J.Gigg, R.Gigg, S.Payne, and R.Conant, J. Chem. S O C . , Perkin Trans. -1,1987, 423. J.Gigg, R.Gigg, S.Payne, and R.Conant, J. Chem. S O C . , Perkin Trans. 1,1987, 1757. J.Gigg, R.Gigg, S.Payne, and R.Conant, 2. Chem. SOC., Perkin Trans. 1, 1987, 2411. K.Praefcke and W.Stephan, Liebigs Ann. Chem., 1987, 645. 1987, 4, 319. C.Jiang, J.D.Moyer, and D.C.Baker, J. Carbohydr. E., K.Kamiyama, S.Kobayashi, and M.Ohno, Lett., 1987, 29. R.R.Schmidt and A.KOhn, Angew. Chem., Int 1987, 26, 482. II.Paulsen, B.Mielke, and B.von Deyn, ~Liebigs Ann. Chem., 1987, 439. H.H.Baer, I.Arai, B.Radatus, J.Rodwel1, and N.Chinh, 9 . J. 1987, 65, 1443. E.Kohne, K.Praefcke, M.Stephan, and P.Marquardt, Chimia, 1986, 5, 248 Abstr., 1987, 107,97015). A.Gomez Sanchez and F.Cabrera Escribano, An. Quim., C, 1986, 82, 124 (Chem. Abstr., 1987, 107,97023). A.Kohn and R.R.Schmidt, Liebigs &. 1987, 1045. R.Blattner and R.J.Ferrier, J. Chem. SOC., Chem. Commun., 1987, 1008. K.-i.Tadano, Y.Ueno, C.Fukabori,Y.Hotta, and T.Suami, Bull. Chem. S O C . Jpn., 1987, 60, 1727. K.-i. Tadano, C.Fukabori, M.Miyazaki, H.Kimura, and T.Suami, B u l l . Chem. SOC. +., 1987, 60, 2189. H.Paulsen and W. von Deyn, Liebigs Ann. Chem., 1987, 125. K.-i Tadano, H.Maeda, M.Hoshino, Y.Iimura, and T.Suami, J. Org. 1987, 52, 1946. K.-i Tadano, Y,Kameda, Y.Iimura, and T.Suami, J . Carbohydr. Chem., 1987, 6, 231. H.Paulsen and W. von Deyn, Liebigs Ann. Chem., 1987, 133. H.Paulsen and W. von Deyn, Liebigs Ann. Chem., 1987, 141. S.Ogawa, Y.Uematsu, S.Yoshida, N.Sasaki, and T.Suami, J. Carbohydr. 1987, 6, 471.

=.,

&.,

=.

s.,

w.. Em.,

m.,

(m.

z.

w.,

e., w.,

Carbohydrate Chemistry

186

81 K.Brewster, J.M.Harrison, T.D.Jnch, and N.Idilliams, J . Chem. SOC., Perkin Trans. 1,1987, 21. 82 S.Ogawa, Y.Shibata, K.Miyazawa, T.Toyokuni, T.Iida, and T.Suami, Carbohydr. Res., 1987, 163,53. 83 A.Klemer and M.Kohla, Liebigs Ann. Chem., 1987, 683. 84 A.Isogai, S.Sakuda, J.Nakayama, S.Watanabe, and A.Suzuki, Agric. Biol. Chem., 1987, 2277. 85 S.Ogawa, Y.Aoki, and T.Tagagaki, Carbohydr. E.,1987, 104,499. 1987, 6,245. 86 K.-i. Tadano, Y.Ueno, Y.Iimura, and T.Suami, J . Carbohydr. 87 K.-i. Tadanc, H.Kimura, M.Hcshino, S.Ogawa, and T.Suami, Bull. Chem. Jpn., 1987, 60, 3673. 88 S.Sicsic, P.I.Ikbal, and F.Le Goffic, Tetrahedron L L . , 1987, 28, 1887. 89 K.-i.Tadano, M.Hoshino, S.Ogawa, and T.Suami, Tetrahedron E., 1987, 28, 2741. 90 T.V.RajanRabu, J. Am. Chem. SOC., 1987, 109. 609. 91 M.R.Hamblin, B.V.L.Potter, and R.Gigg, Biochem. SOC. Trans., 1987, 15,415 (Chem. Abstr., 1987, 107, 78177). 92 M.R.Hamblin, B.V.L.Potter, and R.Gigg, J. Chem. S O C . , Chem. Commun., 1987,626. 93 A.M.Cooke, B.V.L.Potter, and R.Gigg, Tetrahedron Lel., 1987, 2 , 2305. 94 A.M.Cooke, R.Gigg, and B.V.L.Potter, Riochem. SOC. Trans., 1987, 15,904 (Chem. Abstr., 1987, 107, 78176). 95 A.M.Cooke, R.Gigg, and B.V.L.Potter, J. g . ,Chem. Commun., 1987, 1525. 96 J.P.Vacca, S.J.deSolms, and J.R.Huff, J. &. 1987, 109, 3479. 97 C.B.Reese and J.G.Ward, Tetrahedron 1987, 28, 2309. 1987, 28, 4503. 98 S.J.deSolms, J.P.IJacca, and J.R.Huff, Tetrahedron 99 S.Ozaki, Y.Kondo, H.Nakahira, S.Yamaoka, and Y.Watanabe, Tetrahedron 1987. 28. 4691. 100 Y.Wa;aGie, T.Ogasawara, N.Shiotani, and S.Ozaki, Tetrahedron 1987, 28, 2607. 101 D.C.Billington and R.Raker, J. %., Chem.Commun., 1987, 1011. 102 D.C.Billington, R.Baker, J.J.Kulagowski, and I.M.Mawer, 2. Chem. Soc., Commun., 1987, 314. 103 J.C.Lindon, D.J.Raker, Janet M. Williams, and R.F.Irvine, Biochem. J . , 1987, 244, 591 (Chem. Abstr., 1987, 107, 35368). 104 yu. I.Sibrikov, A.E.Stepanov, and V.I.Shvets, 2. Org. Ell., 1986, 1212, (Chem. Abstr., 1987, 106,196708). 105 C.J.Martin a n d W.J.Evans, 2. Inorg. Biochem., 1986, 27, 17 (Chem. Abstr., 1987, 106,18945). 106 B.K.Sathyanarayana and E.S.Stevens, J. Org. 1987, 52, 3170.

z,

m.,

=.

w.

-. =., x., m.,

s.,

m.,

-.

e.

22,

m.,

19 Antibiotics

1 Amino-Glycoside Antibiotics 1 Amino-glycoside antibiotics have been reviewed. Novel insect chitinase inhibitors, allosamidin ( 1 ) and methyl allosamidin (21, have been characterized as pseudo-trisaccharides composed of 2-acetamido-2-deoxy-D-allose attached to a new aminocycl itol derivative a1 losamizol ine ( 3 ) . 2"-N-formamidoylsporaricin A has been isolated from a Saccharopolyspora Hirsuta subspecies,3 A total synthesis of neomycin E has been reported, coupling 4 together neobiosamine and neamine derivatives. A multi (>40) stage synthesis of dibekacin (3',4'-dideoxykanamycin B) has been described, using D-glucose or D-glucosamine prec u r s o r ~ . ~A synthesis of 2' ,3'-dideoxy-kanamycin A has utilized a 6 2',3'-unsaturated intermediate from kanamycin A. HOII,.

Hb (1) R = H ( 2 ) R = Me

Other syntheses reported have included the apramycin analogues 7 and ( 5 ) , 8 and analogues of fortimicins ( 6 ) modified in the sugar ring, a 4'-hydroxy analogue of fortimicin D,9 7'-C-propylfortimicin A, , 7 - ( 3-hydroxypropyl )fort imicin A and its 6 -epimer11 13 7 ' - pheny 1- fort imic in A and its 6 - e p imer , 3 - eno for t imic in D , all involving coupling modified amino-sugars to fortamine derivatives. Another report describes the conversion of maltose to the (4)

188

Carbohydrate Chemistry

fortimicin analogue (7), which shows moderate antimicrobial activity.14 (+I-Validamycin B dodeca-2-acetate has been synthesized from

a resolved furan-acrylic acid Diels-Alder adduct, coupling the epoxide ( 8 ) with valienamine derivative (9), the required regioisomer (10) being the major product (3:2 ratio)(Scheme l)(see also Vo1.18,p.172) . I 5 Analogous procedures were used to make the trehalosamine analogues (11) and (12), racemic pseudo-monosacchar16 ides giving rise to diastereoisomeric mixtures. CH20U

OH

Scheme 2

A series of palmitoyl derivatives of aminoglycoside antibiotics have been prepared, extending previous work on kanamycin A derivatives; all those tested exhibited excellent in vitro antiviral activity. l7 Some acetalation studies on neamine are mentioned in Chapter 18, and a synthesis of the aminoglycoside dehydroxymethylbulgecin A is referred to in Chapter 3 . The loss of the C-4 hydrogen atom of D-glucose in the biosynthesis of the deoxy streptamine ring o f neomycin has been taken to support the intermediacy of a 4-keto-intermediate (13)(Scheme 2). 18

'H and 13C n.m.r. assignments for validamycin A have been reported.I9 Assignments for tobramycin are mentioned in Chapter 21. Fluorescence measurements on Fluram derivatives of some aminoglycoside antibiotics have been recorded; no simple correlation exists between the intensity of fluorescence and the number of free primary amino groups.2 o The activity of aminoglycoside antibiotics against E. Coli have been compared, including N-acyl and !-aminoacyl derivatives of apramycin and nebramine. 21-

189

19: Antibiotics

2 Macrolide Antibiotics Tiacumicins, a complex of 18-membered macrolides produced by a species of Dactylosporangium, has been separated into six components and identified by spectroscopic methods. The major component, tiacumicin B, was assigned structure (14), with the minor components A-F showing minor structural variations in the macrolide ring and the number and esterification pattern of the sugars, which were 22 considered to be rhamnose derivatives.

A genetically-engineered strain of Saccharopolyspora erythraea has been used to produce 2 - n o r - e r y t h r o m y ~ i n s . A ~ ~mutant strain of -~ S. fradiae generates tylosin analogues in which the mycinose sugar unit is converted to 2-demethoxy, 2-demethoxy-4-epi, and 2-0-demethyl derivatives. 24 4'I-g(4-methoxyphenyl)-acetyl-tylosin has been synthesized, in which the terminal mycarose sugar is acylated, the product showing improved resistance to hepatic esterase. 2 5 A new macrolide antibiotic, swalpamycin, elaborated by a strain of 2. anandii, has been characterized as a 16-macrolide with separately attached D-mycinose and D-algarose sugar units. 26 C-2-Fluoro-oleandrosyl fluorides have been synthesized from L-rhamnose (see Chapter 8 > , and then used to glycosylate avermectin Bla monosaccharide to give derivatives with a disaccharide sidechain of generalized formula ( 1 5 ) . 2 7

OMc

f

The mycosamine unit of amphotericin B has been cleaved by a novel oxidation procedure; allylic bromination in the aglycone led presumably to a bromide which cleaved to give an enone and a glycosyl oxonium ion, leading to products considered to have structure (16) (Scheme 3 ) . 28

Carbohydrate Chemistry

190

X = ;NAC or -0

RO

-N

/>-Me

R = SLMe3 R e a g e n t ' L, N D S

Scheme 3

3 Anthracycline and Related Polycyclic Antibiotics New anthracycline antibiotics, A 4 4 7 C and A447 D, have been isolated from S. cyaneus, which contain two trisaccharide chains attached to B-rhodomycinone, the trisaccharide being combinations of rhodinose, rhodosamine, 2-deoxy-fucose, and cinerulose A. Other components of the complex, A447 A and A447 B, proved to be identical with cosmomycins D and C r e ~ p e c t i v e l y . A~ ~further paper on the structure of arugamycin has been published (see Vo1.17, p.176, ref.60). 30 Further components of the ciclamycin complex elaborated by 5 . capoamus have been identified as desamino anthracyclines; ciclamycins 0 and 4 have the trisaccharide units (17) and (18) respectively 31

.

6'

OH

A new class of biosynthetic anthracyclines have been produced by mutant strains of 2. peucetius, which have glucuronic acid attached at 0 - 4 on the anthracyclinone nucleus. 32 Adriamycin and daunorubicin analogues have been reported in which daunosamine is replaced by 2 , 6 - d i d e o x y - 2 - f l u o r o - a - L - t a l o p y r a n o s e 33 and diastereoisomeric 4-acylamino-2,4,6-trideoxy-L-hexopyranoses.34

Anthracyclinones have been synthesized and converted to glycosides using daunosamine (giving 1-deoxy-N,M-demethylpyrromycin),35 4 deoxy-daunosamine ,36 2-deoxy-L-fucose,36y37 and amino-tri- and tetra-deoxy-hexopyranoses. 36 Ij-Alkyldaunorubicin derivatives have been synthesized by Michael addition of the amino-group to substituted maleimides ,38 and by reaction of daunorubicin with dimethylformamide dimethyl acetal and various 1,3-dicarbonyl compounds. 39 3'-Deamino-3'-morpholino derivatives of carminomycins have been

19: Antibiotics

191

r e p ~ r t e d . ~ ’The synthesis of a D-ring indolino analogue of daunomycin is mentioned in Chapter 3 , which also includes a reference to the synthesis of anthracycline oligosaccharides. A new technique of field desorption tandem mass spectrometry has been applied to underivatized cosmomycins, giving spectra which 41 yield sugar sequence information. Further studies on the structure of the angucycline antibiotics urdamycins B-F have been reported; they show minor differences in 42 the aglycone compared with urdamycin A (see V01.20,p.191). New isotetracenone antibiotics, kerriamycins A,R, and C, have been isolated from 5. violaceolatus; these contain rhe aromatic chromophore of aquayamycin ( a C-glycoside) with two or three 0 attached hexose units ( 1 9 ) ; a novel keto-sugar, kerriose (2,6-dideoxy-D-erythro-hexopyranos-3-ulose), is postulated as a component of kerriamycin A. 4 3

4 Nucleoside Antibiotics

A new nucleoside antibiotic arginomycin ( 2 0 1 , isolated from arginensis, is structurally related to blasticidin S.44

S.

NH2

(20.

Nikkomycin Bx ( 2 1 ) and some side-chain analogues have been synthesized by DCC-mediated coupling of the amine and carboxylic acid s ~ b - u n i t s . The ~ ~ oxygen analogue (22) of 61-albomycin has been prepared, building the sugar unit from a xylodialdose derivative using an aldol condensation approach.46 Mono- to tri-acylated derivatives of griseolic acid ( 2 3 ) have been synthesized either by

55':

Carbohydrate Chemistry

192

C02Me

*

OH

(22) R = peptide

OH

unk

selective acylation or selective alkaline hydrolysis of poly-acylated compounds.47 Analogues of griseolic acid have been made in which triflate esters at C - 2 ' or C-7' were displaced by standard nucleophiles (with inversion)(Scheme 4 ) .48 The octose moiety of ezomycins A and A2 has been synthesized as the substituted derivative ( 2 4 ) . 1 4 9 Uridine 5'-aldehyde has been used to prepare modified polyoxin derivatives, g . g . , ( 2 5 ) , by condensation with amines or amino-acid derivatives using trimethylsilylcyanide in presence of boron trifluoride etherate.50 Oxetanocin ( 2 6 ) has been synthesized, Adenineconstructing the oxetan ring as outlined in Scheme 5 . 5 1 ' 5 2 53 modified oxetanocins have also been reported.

NHBz

193

19: Antibiotics

2‘-Deoxy-2’-C-methyl-g-cytidine( 2 7 ) has been synthesized from a keto-nucleoside precursor as shown in Scheme 6.”Lt C I

OEt

Uridine z

w e d s : i,MeMgBr-EtZ0,-500;Li, M e 3 A l o r

M e L i ; G ,McO2CCOCL-DMAP;iv,Bu3SnH;v,F-;W, N H 3 - M e O H

Scheme

6

Analogues of tubercidin, toyocamycin, sangivamycin, and formycin have been prepared (2’-and 3‘-deoxy derivatives, and arabino- and xjr!o- stereoisomers), and tested for antiviral activity; xylotubercidin retained potent activity with reduced cytotoxicity. 55 The glycosylated ribavirin derivatives (28) have been made from 5-2-trityl-ribavirin using a modified Koenigs-Knorr procedure with appropriate glycosyl bromides. 5 6

Showdomycin (29) has been prepared in high enantiomeric purity from the chiral Diels-Alder adduct (30) as indicated i.n Scheme 7,57 the latter stage having been previously reported for the racemic compound (see Vol. 14, p.162). The imidazole nucleoside derivative (31) has been used to prepare the P -D-ribofuranoside of azepinomycin ( 3 2 ) . 5 8 Facile syniiheses have also been reported for tubercidin (7-deazaadenosine) ,lnd related 7-deazaguanosine nucleosides by sodium salt glycosylation

Carbohydrate Chemis try

194

procedures.5 9 A study of the biosynthesis of 2'-deoxycoformycin ( 3 3 ) indicates that C-7 is derived from C - 1 of D-ribose, and not from C - 3 of serine, using I 3 C labelling experiments; an enzyme was also isolated which reduces the intermediate 8-ketocoformycin.6 0 The cyclopentadiene analogue of the chiral Diels-Alder adduct ( 3 0 ) has been used to make aristeromycin ( 3 4 ) and neplanocin ( 3 5 ) as outlined in Scheme 8 .61 7-t-Butoxynorbornadiene has been converted to racemic 6'-/3-hydroxy-aristeromycin( 3 6 ) by conventionalmethods.6 2

or 0'-

s:

CHZ

O H OH

py R = rnenthyl

(34)

(35)

Scheme 8

Analogues ( 3 7 ) of neplanocin A have been synthesized from either D-ribonolactone or D-mannose which were used to make enantiomeric uronic acid lactones ( 3 8 1 , leading to the analogues as shown in Scheme 9 . 6 3 Another group has used the isopropylidenated cyclopentenone ( 3 9 ) to make (-)-neplanocin A by a similar procedure. 6 4

O - c ? O x 0

(+I (39)

Mo M . O

.ON *

O x 0

(4.0)

Standard procedures have a l s o been used to prepare a number of

195

19: Antibiotics

neplanocin A analogues from the amino-cyclopentene (401, including imidazole and uracil analogues as well a s 2'-deoxy, 2,2'-anhydro, and =-compounds. 6 5 A study of the biosynthesis of sinefungin using a cell-free extract of 2. incarnatus suggests the immediate precursor to be L-arginine, and a biosynthetic scheme is proposed.66 5 Glycopeptide Antibiotics The chemistry of the vancomycin group of antibiotics has been reviewed. 67 New compounds reported include the chloropolysporins A-C, produced by a strain of Faenia interjecta, ;\+ich possess a cyclic polypeptide core with attached D-glucose, D-mannose, and L-ristosamine, and additionally L-rhamnose in A and 5 , and D-galactose in and parvodicins, obtained from a new strain of Actinomadura parL'osata, which also have a cyclic polypeptide core with attached - I l - t ~ ~ ~ n o pyranose and 2-acylamido-2-deoxy-~-D-glucopyranosyluronic acid residues, the components differing in the nature of the C 9 - C I 1 fatty acid units attached to the amino group and whether or not the C-6 hydroxy group of mannose is acetylated.69 Actinoidin A2 differs from actinoidin A in having rhamnose in place of acosamine, otherwise similarly containing D-glucose, D-mannose and L-actinosamine attached to a peptide core;70 a 2D n.m.r. study on these tho antibiotics has been reported. 7 1

6 Miscellaneous Antibiotics

OH

OH

(4')

""Q -""go. H0

+Ho$@N"

HO

OH NHCONYz

(44)

HNK NH O

(421

Scheme 1 0

HN-k

(43)

0

196

Carbohydrate Chemistry

Galactostatin ( 4 5 ) , a new p-galactosidase inhibitor obtained from S. lydicus, is the latest member of the 5-amino-5-deoxy-hexose series of enzyme inhibitors.74

:ono...

CH20H

2"'

oy

co

OH

(45)

(46)

n,Son, cL

A chlorothricin relative, 2"'-hydroxychlorothricin ( 4 6 , part structure) has been isolated from a culture of S. sp.KS18; it contains 6-deoxyglucose in place of 2,6-dideoxy-D-glucose in the disaccharide unit. 75 Paldimycins A and B, and also antibiotic 273a2, have been obtainpaulus which also produces paulomycins ed from fermentations of A and €3 (see V01.20, p.30); the paldimycins contain one (R) or two (A) units of 5-acetyl-L-cysteine attached to the non-carbohydrate ~ ~ they can be prepared from the portion of the p a u l ~ m y c i n s ,and latter by reaction with this amino-acid. 77 New streptothricin antibiotics, AN-201 1-111, elaborated by 2. nojirienis, have been characterized as NB-acylated derivatives of streptothricins D-F, carrying acetyl groups in the B-lysine peptide side-chain in these compounds.7 8 (For streptothricin F , see Vol . 1 6 , p.199). A total synthesis of the spiro-C-glycoside core (47) of the papulacandins has been described, summarized in Scheme 11; unusually, a non-carbohydrate Diels-Alder adduct is systematically hydroxylated to build up the D-glucose ring.79 Derivatives of papulacandin R

s.

OMS

197

19: Antibiotics

have been prepared; some 0-10 alkyl ether and C-11 acylamincl derivatives (substituents in the aromatic ring) show improved antibiotic activity 80 The anti-tumour glycoside (-)-phyllanthostatin (48) has been synthesized by preparing the 6-deoxy-D-glucose ,6- 1+2 linked disaccharide conventionally and coupling the free sugar to the aglyconic carboxylic acid using t r i p h e n y l p h o s p h i n e - d i i s o p r o F y l azodicarboxylate; chloroacetyl protecting groups were selectively removed in presence of the acetyl groups without acetyl migration 81 using hydrazine dithiocarbonate.

.

0 CL R a g e d 6 i, O U L L , ~ ,ArCOGL,iLi> U,-P&/LIc

OH

(48)

S c h e m e 12

Stepwise degradation of the oligosaccharide chain in moeromycin A has been accomplished in connection with structure-activity studies; standard periodate cleavage of diol structures was combined with Barry degradation or p-elimination chemistry. 82 Ellagitannins possessing a dimeric structure with several galloyl groups on the glucose core display marked antitumour activity, apparently by potentiation of the host's immunity. 83 The methyl glycoside of curacin (49)(the chromophoric terminus of several orthosomycin antibiotics) has been prepared as shown in Scheme 12; the 3-2-substituted isomer was obtained similarly.84

FAB-m.s. has been applied to the sugar sequence analysis of octasaccharide everninomicin antibiotics. 5 5 9-Hydroxyellipticene N-glycosides, which can show high antitumour activity, are mentioned in Chapter 10. References 1

2 3

4

S.Umezawa, S.Kondo, and Y.Ito, Biotechnology, 1986, 4, 309 (Chem. Atstr., 1987, 107, 51160). S.S.Akuda, A.Isogai, T.Makita, S.Matsumoto, K.Koseki, H.Kodama, and A.Suzuki, Agric. Biol. Chem., 1987, 2, 3251. H.Umezawa, S.Gomi, Y.Yamagishi, T.Obata, T.Ikeda, M.Hamada, and S.Kcndo, J. -Antibiot., 1987, 5, 91. T.Usui and S.Umezawa, 2. Antibiot., 1987, 5, 1464.

Carbohydrate Chemistry

198 5 6 7 8 9

10 11 12 13

14 15 16 17 18 19 20 21 22 23 24 25

26 27 28 29 30 31 32 33 34 35 36 37 38

M.Yoshikawa, M.Torihara, T,Nakae, B.C.Cha, and I.Kitagawa, Chem. Pharm. Bull., 1987, 35, 2136. Y.Kobayashi, T.Tsuchiya, S.Umezawa, T.Yoneta, S.Fukatsu, and H.Umezawa, K . Chem. %. +., 1987, 60, 713. A.Canas-rodriguez and L.A.Corone1-Borges, Carbohydr. &., 1987, 165, 129. A.Canas-Rodriguez, S.G.Ruiz-Poveda, and L.A.Corone1-Borges, Carbohydr. Res. 1987, 159, 217. K.Kanai, I.Sakamoto, Y.Miyamoto, S.Ogawa, and T.Suami, Bull. Chem. 1987, p0, 255. 1987, 60, K.Kanai, J.Nishigaki, S.Ogawa, and T.Suami, Bull. Chem. SOC. 261. K.Kanai, J.Nishigaki, T.Taki, S.Ogawa, and T.Suami, Carbohydr. E.,1987, 170, 47. K.Kanai, S.Ogawa, and T.Suami, Bull. Chem. SOC. 1987, 60, 2079. 1987, 60, 1532. K.Kanai, S.Yokoi, S.Ogawa, and T.Suami, Bull. Chem. S O C . N.Sakairi, M.Hayashida, and H.Kuzrihara, Tetrahedron E . , 1987, 28, 2871. S.Ogawa and Y.Miyamoto, J. Chem. S O C . , Chem. Commun., 1987, 1843. S.Ogawa and Y.Shibata, Carbohydr. &., 1987, 170,116. K.Matsuda, N.Yasuda, H.Tsutsumi, and T.Tanaya, J. Antibiot., 1987, 40, 843. S.K.Goda and M.Akhtar, J. Chem. SOC., Chem. Commun., 1987, 12. W.-Z.Jin, K.L.Rinehart, Jr., and T.Toyokuni, J. Antibiot., 1987, 5 , 329. M.Breitinger, K.K.Mayer, and W.Weigrebe, Arch. Pharm. (Weinheim, K.), 1986, 319, 1135 (Chem. Abstr., 1987, 106,50583). N.E.Allen, W.E.Alborn, J r . , H.A.Kirst, and J.E.Toth, 2. Med. Chem., 1987, 30, 333. J.E.Hochlowski, S.J.Swanson, L.M.Ranfranz, D.N.Whittern, A.M.Buko, and J.B.McAlpine, J. Antibiot., 1987, 40, 575. J.B.McAlpine, J.S.Tuan, D.P.Brown, K.D.Grebner, D.N.Whittern, A.Buko, and L.Katz, J . Antibiot., 1987, 40, 1115. K.Kiyoshima, K. Tanada, M. Yamamoto, K Kubo , R. Okamoto , Y. Fukagawa, T. Ishikura , H.Naganawa, T.Sawa, T.Takeuchi, and H.Umezawa, J . Antibiot., 1987, 5, 1123. T.Takeuchi, T.Sawa, H.Naganawa, M.Hamada, H.Umezawa, T.Yoshioka, K.Kiyoshima, H.Iguchi, M.Sakamoto, Y.Shimauchi, H.Tone, Y.Fukagawa, and T.Ishikura, J.-Antibiot., 1987, 40, 1358. S.Chatterjee, G.C.S.Reddy, C.M.M.Franco, R.H.Rupp, B.N.Ganguli, H.-W.Fehlhaber, and H.Kogler, J. Antibiot., 1387, 40, 1368. C.Bliard, F.C.Escribano, G.Lukacs, A.Olesker, and P.Sarda, J . Chem. Commun., 1987, 368. -~ K.C.Nicolaou, T.K.Chakraborty, R.A.Daines, and Y.Ogawa, J . Chem. SOC., Commun., 1987, 686. A.Shimosaka, Y.Hayakawa, M.Nakagawa, K.Furihata, H.Seto, and N.Otake, J . AntiBiot., 1987, 5, 116. H.Kawai, Y.Bayalrawa, f",.Nakagawa,K.Furihata, H.Seto, and N.Otake, J . Antibiot., 1957, 1273. S B i e b e r , A.A.Da Silva Filho, J.F.De Mgllo, 0.G.De Lima, M.S.Do Nascimento, H.J.Veith, and W. Von Der Saal, J . Antibiot., 1987, 40, 1335. G.Cassinelli, M.Ballabio, A.Grein, S.Merli, G.Rivola, F.Arcamone, B.Barbieri, and T.Bordoni, 2. Antibiot., 1987, 40, 1071. K.Ok, Y.Takagi, T.Tsuchiya, S.Umezawa, and H.Umezawa, Carbohydr. 1987, 169, 69. A.Martin, C.Monneret, and M.Pias, Carbohydr. 1987, 166,59. C.M.Wong, Y.Yan, and H.Y.P.Lam, Kangshengsu, 1986, 11,398 (Chem. Abstr., 1987, 107, 59 373). 161 (Chem. Abstr., J.P.Gesson and M.Mondon, Actual. Chim. Ther., 1986, 2, 1987, 107, 59372). H-Dufat-Trinh Van, E.Seguin, F.Tillequin, and M.Koch, Heterocycles, 1987, 26, a79. A.Czerwinski, W.A.Kanig, S.Martelli, P.Sowinski, M.Bontemps-Gracz, C.Mtihringer, P.Kolopziejczyk, and E.Borowski, J. Antibiot., 1987, 40, 1067.

z. *.,

+.,

+.,

*.,

.

m.e.,

e.

c,

=.,

=.,

19: Antibiotics 39

199

B.Stepanska, E.Borowski, L.Falkowski, and S.Fartelli, pol. J. Chem., 1986, 60, 525. -

40 H.Umezawa, S. Nakajima, H.Kawai, N.Komeshima, H.Yoshimoto, T.llrata, A.Odagawa, N.Otsuki, K.Tatsuta, N.Otake, and T.Takeuchi, J. Antibiot., 1987, GO, 1058. 41 K.Hirayama, S.Akashi, T.Ando, I.Sorino, Y.Etoh, H.Morioka, H.Shibai, and A.Yurai, Biomed. Environ. Mass Spectrom., 1987, 14,305 (Chem. Abstr., 1987, 107, 198 792). 42 J.Rohr and A.Zeeck, J . Antibiot., 1987, 40, 459. 43 Y.Bayakawa, K.Adachi, T.Iwakiri, K.Imamura, K.Furihata, H.Seto, and N.Otake, Agric.Biol. 1987, 51, 1397. 44 A.D.Argoudelis, L.Baczynskyj, M.T.Kuo, A.L.Laborde, O.K.Sebek, S.E.Truesdel1, and F.B.Shilliday, J. Antibiot., 1987, 40, 750. 45 H.Hahn, H.Heitsch, R.Rathmann, G.Zimmermann, C.Bormann, H.ZBhner, and W.A.KOnig, Liebigs Ann. Chem., 1987, 803. 46 H.Paulsen, M.Brieden, and G.Benz, Liebigs Ann. Chem., 1987, 565. 47 Y.Murofushi, M.Kimura, Y.Iijima, M.Yamazaki, and M.Kaneko, Chem. Pharm. B u l l . , 1987, 35, 1036. 48 Y.Murufushi, M.Kimura, Y.Iijima, M.Yamazaki, and M.Kaneko, Chem. Pharm. Bull., 1987, 35, 4442. 49 O.Sakanaka, T.Ohmori, S.Kozaki, and T.Suami, Bull. Chem. SOC. .JJ., 1987, 3, 1057. 50 J.Fiandor, M. -T.Garcia-L&pez, F.G.De Las Heras, and P.P.M;ndez-Castril I&, Synthesis, 1987, 978. 51 S.Niitsuma, Y,Ichikawa, K.Kato, and T.Takita, Tetrahedron E . , 1987, 28, 3967. 52 S.Niitsuma, Y,Ichikawa, K.Kato, and T.Takita, Tetrahedron 1987, 28, 4713. 53 M.Shimada, S.Hasegawa, S.Saito, T.Wishikiori, A.Fujii, and T.Takita, J. Antibiot., 1987, 40, 1788. -~ 54 A.Matsuda, K.Takenuki, H.Itoh, T.Sasaki, and T.Ueda, Chem. Pharm. Bull., 1987, 35, 3967. 55 E.De Clercq, J.Balzarini, D.Madej, F.Hansske, and M.J.Robins, J . E d . M., 1987, 30, 481. 56 N.B.Hanna, R.K.Robins, and G.R.Revankar, Carbohydr. E.,1987, 165, 267. 57 H.Takayama, A.Iyobe, and T.Koizumi, Chem. Pharm. Bull., 1987, 35, 433. 58 K.Isshiki, Y.Takahashi, H.Iinuma, H.Maganawa, Y.Umezawa, T.Takeuchi, and H.Umezawa., J.Antibiot., 1987, 40, 1461. 59 K.Ramasamy, N.Imamura, R.K.Robins, and G.R.Revankar, Tetrahedron Lett., 1987, 28, 5107. 60 J.C.Hanvey, E.Sma1, R.J.Suhadolnik, and D.C.Baker, Nucleosides Nucleotides, 1987, 5, 495. 61 Y.Arai, Y.Hayashi, M.Yamamoto, H.Takayama, and T.Koizumi, Chem. Lett., 1987, 185. 62 A.Ben Cheikh and J.Zemlicka, Nucleosides Nucleotides, 1987, 6, 265. 63 D.R.Borcherding, S.A.Scholtz, and R.T.Borchardt, J. Org. 1987, 52,5457. 64 J.R.Medich, K.B.Kunnen, and C.R. Johnson, Tetrahedron g., 1987, 25, 4131. 65 M.Arita, T.Okumoto, T.Saito, Y.Hoshino, K.Fukukawa, S.Shuto, M.Tsujino, H.Sakakibara, and M.Ohno, Carbohydr. g . ,1987, 171,233. 66 H.Malina, C.Tempete, and M.Robert-Gero, J. Antibiot., 1987, 40, 505. 67 G.S.Katrukha and A.B.Silaev, Chem. Pept. Proteins, 1986, 3, 289 (Ch'zm. Abstr., 1987, 107,40279). 68 T.Takatsu, S.Takahashi, M.Nakajima, T.Haneishi, T.Nakamura, H.Kuwanl3, and T.Kinoshita, J. Antibiot., 1987, 40, 933. 69 S.B.Christensen, H.S.Allaudeen, X.R.Burke, S.A.Carr, S.K.Chung, P.Dl:phillips, J.J.Dingerdissen, M.Dipaolo, A.J.Giovenella, S.L.Heald, L.B.Killmer, B.A.Mico, L.Mueller, C.H.Pan, B.L.Poehland, J.B.Rake, G.D.Roberts, M.C.Shearer, R.D.Sitrin, L.J.Nisbet, and P.W.Jeffs, J. Antibiot., 1987, 40, 970. 70 J.J.Dingerdissen, R.D.Sitrin, P.A.Dephillips, A.J.Giovenella, S.F.G::appel, R.J.Mehta, Y.K.Oh, C.H.Pan, G.D.Roberts, M.C.Shearer, and L.J.Nisbei:, J.-Antibiot., 1987, 40, 165. 7 1 S.L.Heald, L.Mueller, and P.W.Jeffs, J. Antibiot., 1987, 40, 630.

e.,

m.,

e.,

Carbohydrate Chemistry

200 72 73 74 75 76 77 78 79

80 81 82 83

84 85

S.Kiyoto, H.Murai, Y.Tsurumi, H.Terano, ?I.Kohsaka, S.Takase, I.Uchida, M.Hashimoto, H.Aoki, and H.Imanaka, J . Antibiot., 1987, 40, 290. T.Yasuzawa, M.Yoshida, E.Ichimura, K.Shirahata, and H.Sano, 2. Antibiot., 1987, 40, 727. Y.Mitake and M.Ebata, J. Antibiot., 1987, 40, 122. I.Yamamoto, M.Nakagawa, Y.Hayakawa, K.Adachi, and E.Kobayashi, 2. Antibiot., 1987, 40, 1452. A.D.Argoudelis, L.Baczynskyj, J.A.Buege, V.P.Marshal1, S.A.Mizsak, and P.F.Wiley, J.-Antibiot., 1987, 9, 408. A.D.Argoudelis, L.Baczynskyj, S.A.Mizsak, F.B.Shilliday, P.A.Spinelli, and J.Dezwaan, J. Antibiot., 1987, 40, 419. T.Ando, S-Miyashiro, K.Hirayama, T.Kida, H.Shibai, A.Murai, and S.Udaka, J. -Antibiot., 1987, 40, 1140. 1987, 171,317. S.Danishefsky, G.Phillips, and M.Ciufolini, Carbohydr. P.Traxler, W.Tosch, and O.Zak, J. Antibiot., 1987, 40, 1146. A.B.Smith 111, K.J.Hale, and H.A.Vaccaro, J. Chem. Commun., 1987, 1026. P.Welze1, F.Kunisch, F.Krugge1, H.Stein, J.Scherkenbeck, A.Hi1tmann. €l.Duddeck, D.MUller, J.E.Maggio, H.-W.Fehlhaber, G.Seibert, Y. van Heijenoort, and J. van Heijenoort, Tetrahedron, 1987, 43, 585. K.Miyamoto, N.Kishi, R.Koshiura, T.Yoshida, T.Hatano, and T.Okuda, Chem. 1987, 2, 814. Pharm. P.Jutten, J.Dornhagen, and H.-D.Schar€, Tetrahedron, 1987, 43, 4133. B.N.Pramanik and A.K.Ganguly, Indian 2. Sect 3, 1986, 1105 (Chem. Abstr., 1987, 107,96997).

e.,

w.=.,

w.,

m.,

z,

20 Nucleosides

1 Svnthesis

Standard condensation procedures have been used to prepare 8-Dribofuranosyl derivatives of 5-fluoro-6-methyluracil, fluorinesubstituted 4-amino -2 (1g)-pyridones, various pyridazinones, astriazene derivatives of type (1), 4-substituted-3-hydroxypyrazoles such as (2),5 and some diazepinones including the homocytidine ( 3 ) .6 Some quinolinium nucleosides have been reported, N? aryl-2-methyl adenosines have been prepared by the fusion method,8 and improved

routes have been developed for the synthesis of 7-methyl-8-oxoguanosine’ and 1-deazaadenosine.10 The use of 2-~-acetyl-6-g-diphenylcarbamoylguanine in Vorbruggen - type couplings ensures the formation of 9-glycosyl guanine nucleosides in the B-D-ribo-, a-D-arabino- and B-D-xylofuranosyl series.l1 Both ribofuranosylpurines and -pyrimidines can be formed from 1fluorofuranoses and silylated bases in the presence of SiF4, 2-acyl protection ensuring B-D-isomers. l2 Various isoguanosine nucleosides related to doridosine, such as ( 4 ) , were prepared via glycosylation of 6-amino-2-mercaptopurine, and a further report has appeared on the synthesis of glycosides of pyrazin0[2,3-~]-1,2,6-thiadiazine-2,2-dioxides (see Vol 20, p202) ;l4 the riboside (5) of the related imidazo[4,5-c]-1,2,6-thiadiazine2,2-dioxide system has been synthesized. 15 The stereospecific sodium salt glycosylation procedure was used to prepare the ribofuranosylpyrrole (6) via the reaction between 2,3-g-isopropylidene-5-~-t-butyld~methyls~lyl-a-~-r~bofuranosyl chloride and the salt of 2-cyanopyrrole.16

Carbohydrate Chemistry

202

l-B-D-Arabinofuranosides of 4-substituted pyrazolo[3,4-d]pyrimi-

dines have been prepared either by direct glycosylation or by inversion of the 2 -configuration in a B-D-ribofuranoside, l7 and bD-arabinofuranosylcytosine has been made by the novel method out18 lined in Scheme 1.

OH

OH

Use of the sodium salt glycosylation method gave rise to p-Darabinofuranosylpyrroles and analogous 2 -deoxy systems, (see also Vol 20, p.203), and such a 2-cyanomethyl-3-ethoxycarbonyl pyrrole was further converted to the pyrrolopyridine (3,7-dideazaguanine) nucleoside (7). 2 0 A similar reaction between the 2,4-dichloroheterocycle and 2,3,5-tri-g-benzyl-a-D-arabinofuranosyl chloride led to some pyrrolo[ 3,2-:]pyrimidines such as ( 8 ) 21 A transglycosylation procedure has been used to convert guanosine into 9-B-D-xylofuranosylguanine ,22 whilst the systematic synthesis of a- and B-D-lyxofuranosyl nucleosides of the five common nucleobases has been reported: a-anomers were obtained by direct glycosylation using tetra-9-acetyl-a-D-lyxofuranose, and the Banomers by oxidation-reduction of 3', 51-O-TIPDS-~-D-xylofuranosyl systems.23 An account of a plenary lecture reviews the work of this group on both lyxo- and xylofuranosyl systems (see Vol 20, p.203-4), 24 and a paper on analytical aspects of these compounds is mentioned in Chapter 23. A standard condensation was used to prepare the B-D-glucopyrano-

.

203

20: Nucleosides

I

p -D - G k - p (9)

syl-1,2,6-thiadiazine (9), the peracetyl derivative of which exists as rotationally-restricted syn - anti conformers at room temperat~re; a ~similar ~ study was carried out on the related bicyclic compound (10) 26 Glycopyranosyl 7-azaindoles (11) have been reported, via standard glycosylations. 27

.

2 Anhvdro- and Cvclonucleosides 2,2'-Anhydro-6-azauridine (12), and its 5I-deoxy analogue, were formed when the appropriate 21,31-cycliccarbonate was treated w i t h imidazole in DMF; alkaline hydrolysis gave the arabinofuranosyl nucleosides.28 When the 2 '-triflate (13) was treated with various nucleophiles, the products obtained were those of interconversion into 2,2'-anhydro nucleosides of type (14, X = OAc, C1, Br, N3). 29

CH20H

k?

O x 0 i, 3NDS-DMF, r t . ; G ,

Reoyds:

u .

L

MeONa

Scheme 2

2 04

Carbohydrate Chemistry

Scheme 2 illustrates a good route to 5l-0, 6-cyclo -5,5-dihalogeno5,6-dIhydropyrimidine nucleosides; in the uridine case shown, elimination of HBr occurred readily with base as indicated.30 NHCOR

Cyclonucleosides of type (15, R' , R2 = H, Me) were prepared by reaction between 2,3-g-isopropylidene B-D-ribofuranosylamine tosylate and R1R2C (NCS)CH2CH0.31 The g2, 5 I -anhydride of BVDU (16) has been reported and shown to have good antiviral activity.32 It has been demonstrated that N6-acyl derivatives of 5 -0, 8-cycloadenosines (17) can be cleaved reductively to the corresponding adenosines by sodium cyanoborohydride. 33 When 3', 5'-di-g-tosylthymidine was treated with methylamine or ammonia at 35O, the 2,5'-imino compounds (18, R=H,Me) were formed in high yield (Scheme 3). The 2,3'-anhydronucleoside was presumed to be an intermediate, and (18) underwent hydrolysis to the aminonucleosides (19) 34

.

0Ts

('81

Scheme 3

A further account has been given of the formation of 3',5'epithio-3~,5~-dideoxy-l-~-xylofuranosylurac~ls mentioned last year (Vol 20, p.204). 35 Free radical methodology has been used to prepare some 6,5'cycl0-5~-deoxypyrirnidine nucleosides, as illustrated by the sequence in Scheme 4,36 whilst cyclonucleoside (20), previously made by such an approach (see Vol 16, p.207-8) has been converted into the 37 higher-sugar analogue (21) (Scheme 5).

205

20: Nucleosides 0

8:

L

OAG

0 Ac Reagents:

L,

OH

Bu3SnHrAIBN ; u , N a O M e

Scheme 4 0 C02Et

A

H

An intramolecular glycosidation was used as a key step in the route to some 21-deoxy-6,31-methano-cyclopyrimid~nenucleosides 38 (Scheme 6); the 2I-oxygen was removed by free radical reduction. $ Me I

OMe

h

HO

---+ OH Scheme

6

A papar on the hydrolysis of purine 51-cyclonucleosides is mentioned in Section 14. 3

Deoxynucleosides

5I-Deoxyinosine has been isolated from the urine of patients with 39 chronic myelocjenous leukaemia. It has been shown that the stereoselectivity in the reaction between a 2,4-bis(trimethylsilyloxy)pyrimid~ne and 3,S-di-g-pchlorobenzoyl 2-deoxy-a-D-ribofuranosyl chloride depends on the reaction conditions; in the presence of p-nitrophenol, 2'-deoxy-B-

206

Carbohydrate Chemistry

uridines are produced with high stereoselectivity, whilst with pnitrophenol and pyridine present, a-isomers are favoured.40' 41 Standard procedures have been used to prepare 2'-deoxy-a-and pD-ribofuranosides of 5- (2,2-difluorovinyl) and 5- (2-haloalkyl)uracils,43 and 1- (2'-deoxy-p-D-ribofuranosyl) -1g-benzimidazole has been obtained by deoxygenation of the 3',5'-TIPDS derivative of the ribonu~leoside.~~ The use of the Fmoc group to protect the sugar hydroxyls gave an improved overall yield of 2'-deoxy-5-azacytidine, as a result of the mild basic conditions required for deprotection. 45 The use of phase-transfer glycosylation with 2-deoxy-3,5-di0-toluoyl-a-D-ribofuranosyl chloride has led to the synthesis of 2-amino-2I -deoxytubercidin (22),46 5-aza-7-deaza-2I -deoxyguanosine ( 23 ) ,47 and 2 -deoxyribofuranosides of some pyrrolo [ 3,2-5J pyridines

.

(3,7-dideazapurines) 48 In a plenary lecture, Seela has reviewed some of his work in this area.49 The related homogeneous sodium salt glycosylation procedure was used to prepare 2,4-dibromoand -dichloro-9-(2I -deoxy 4-D-ribofuranosyl)purine,50 and 2 I deoxyribavirin (24), which was further reduced in a Barton-type reaction to the 2 ,3 I -dideoxyanalogue (25) 51 Tributylstannane was similarly used for stepwise deoxygenation to give 2',3'-dideoxy derivatives of various 5-substituted uridines and cytidines, and also of 5-azacytidine. 52 A range of other 2 ,3 -dideoxynucleosides and 3I-substituted -2',3'-dideoxynucleosides have been reported as potential anti-HIV agents.53 2~-Deoxy-2~,2t-dideuterionucleosides, required for studies of DNA conformation by n.m.r. methods, have been synthesized by the two routes outlined in Scheme 7 (see Vol. 20, p.208 for an enzymic route to such compounds),54 whilst 2 ,2 I , 3 ,4 I -tetradeuterio-2 deoxynucleosides can be made by treating methyl B-D-arabinopyranoside with Raney nickel in D20 to give the 2,3,4-trideuterio compound 55 and then further manipulations similar to those in Scheme 7.

.

Deuteriation or tritiation of 2~-deoxynucleosidesat the 5'-

20: Nucleosides

ReagdS

L,

NaBD,,

207

b,

PhOCSCL-DM4P,

UL

Du3SnD AIBN,

W , L L A L D ~v. ,

N a H - t S 2 Me1

Scheme 7

position has been carried out by borodeuteride/tritiide reduction of a 5'-aldehyde, and epimerization of such an aldehyde in D20/tri56 tiated water serves to label the 4'-position. Some 21-deoxy-p-D-ribo-hexopyranosyl nucleosides have been prepared from silylated bases and the peracylated sugar, this method giving the p-anomers in good yield,57 and a range of 6'-deoxyhexo58 pyranosyl nucleosides of adenine have been reported. Some deoxyanalogues of tubercidin are referred to in Chapter 19. 4 Halonucleosides An improved synthesis of the antiherpes agent 2'-deoxy-2'-fluoroB-D-arabinofuranosyl derivatives of some 5-(2-haloalkyl)uracils have been synthesized,43 as have various 2 - and 3 -fluorinated 2 I , 3 dideoxypentofuranosyladenines 6o Standard routes were used to prepare various 5l-modified analogues of 2'-deoxy-2'-fluoroarab~nofuranosylpyrimidines,61 and the synthesis of 5-halo-1-(2 -f luoro2 -deoxy-B-D-ribofuranosyl) [ 2-14C Juracils was carried out by ring opening of 2,2'-anhydroarabinofuranosyl systems.62

.

An account of a plenary lecture describes routes to 2',2'63 and 31,31-difluoronucleosides. Whilst direct displacement of the 2'-?-triflyl group in (26) could be effected, attempts to hydrolyse the anhydro-linkage resulted in formation of an unsaturated chloronucleoside (Scheme 64 8)

R e a g e n t s : i , LLCL

- ti M PA ;U , OHScheme

8

Carbohydrate Chemistry

208

-

A range of unprotected nucleosides, such as uridine or adenosine, have been brominated or iodinated at the 5'-position in high yield by the use of the carbon tetrahalide and triphenylphosphine in dimethylacetamide or HMPA. 65

5 Amino- and Azidonucleosides The synthesis of the aminonucleosides (19) was described earlier. 3 4 A general method for the synthesis of 3I-azido -2I,3l-dideoxyribofuranosyl nucleosides involves the reaction of methyl 3-azido2,3-dideoxy-5-~-toluoyl-D-ribose with the nucleoside base in the presence of TMSOTf. 66 A range of 3 I -azido- and 3 I -amino-2 ,3 I dideoxypyrimidine ribonucleosides have been prepared and evaluated as antiviral agents. 67 A study has been carried out on the reaction shown in Scheme 9, and the reasons for the variation in isomer ratio was discussed (see

+

OH

)----k

r

(27)

N3

Scheme 9

also Vo1.18, p.198). The minor isomer (27) was isolated and deprotected to give 1-(2-azido-2-deoxy-/3-D-xylofuranosyl)uracil.68 21-Azido-2~,31-dideoxyadenosine(28) has been made for the first time via the chemistry of Scheme 10; the 2I-keto intermediate is postulated to arise from (29) by a 1,2-hydride shift, and from (30) by /3-elimination and detosylation. 69

ryH < rq w?'

1 . 5 0

(29)

Mso

OTS

(39

~

0

R - U G

L,

UL,

-

DM TT0C H2 b A d N 6 D M T& - rL " 3'

~

2'

N3

Mg ( O M e ) 2 - N ~ b t + -G 6 ~ /MeOu, 6 u.,p1sc~py Nahlg- DrlF,

W,

,

(28)

HOAc-H20

Scheme 10

Secrist, in a plenary lecture, has described the synthesis of new substrate analogues as inhibitors of 2-adenosylmethionine decarboxylase. The compounds made were of type (31), where E is a nucleophilic end group designed to react with the pyruvoyl group at the active site.70

20: Nucleosides

209

Various bromoacetylamido nucleosides (32) have been reported as 71 potential inhibitors of nucleoside biosynthesis.

6 Thionucleosides

The xylofuranosyl analogue of methylthioadenosine (33) has been isolated from the marine nudibranch Doris verucosa, thus providing evidence for the existence in nature of analogues of 5-adenosylmethionine. 72 S-Formycinyl-L-homocysteine has been prepared via 5I-chloro5'-deoxyformycin (Vol 20, p.212), and the 3I-deoxy analogue was also reported. 72 A thioglycoside of cytidine is mentioned in Chapter 11. 7 Branched-chain nucleosides The 2-C-methyl ribose derivative (34) has been prepared in two ways, as outlined in Scheme 11; this intermediate underwent Vorbruggentype coupling to give, after deprotection, 2'-C-methylnucleosides, but the rate of reaction was very slow.74r75 CHZOH

ToLocbA vo7 ~

D-GLUGOSE.

-++ H

-++

M~ o

b

o

ODn

o+-

~

CH20Tr

HOH,~ AcO

OH t D-Ribose

OAc

(34) Scheme 1 1

O

x

0

Branched-chain nucleosides have been synthesized by reaction of organometallic reagents with ketonucleosides. The 3I-keto compound (35) reacted satisfactorily with organolithium or organoaluminium reagents whilst the 2I-ketouridine (36) reacted well only with the latter (Scheme 12) .76 However, other workers have found that the 2t-ketonucleosides(37) reacted with a Grignard reagent to give

Carbohydrate Chemistry

210

21 R

S c h e m e 12

ultimately 2'-deoxy-2'-(~)-methylcytidine (38) (Scheme 13); when (37) reacted with methyl lithium or trimethylaluminium, the 2'epimer was formed. The free radical deoxygenation to give (39) was stereospecific, and the 2I-epimer also gave (39) as the major isomer (3:l). 77 The 2'-C-methyl analogue (40) of cordycepin was similarly prepared by Grignard addition to a 2'-ket0ne,~~ whilst the 3'methyl analogue (41) was made by copper-catalysed Grignard opening of an e~oxide.~' Epoxide opening was also used to prepare a range 80 of branched-chain uracil nucleosides of type (42).

8 Nucleosides of Unsaturated Sugars, Ketosugars and Uronic Acids

The unsaturated nucleoside (43) was formed during ortho-lithiation of the corresponding 2 I , 3 -2-isopropylidene ribonucleoside.81 1I ,2 ' Unsaturated nucleosides and 3~-deoxy-2~-ketonucleosideswere amongst

2 0: Nucleosides

21 1

the products of reaction of 2'-g- and 3'-g-tosylated adenosines with Grignard reagents: this paper describes a convenient route to 3'deoxy-2'-ketoadenosine. 82 The glycosidation of xanthine and guanine with 1,2,5-tri-gacetyl-B-D glucofuranurono-6,3-lactone gives N-9 and N-7 glycosides mainly: 6I-amides were accessible by ammonolysis of the lactones.83 9 C-Nucleosides

review in Japanese has appeared on the chemistry of C-nucleosides, with the methodologies employed in synthesis categorized into four groups. 84 The pyridine C-nucleoside (44), an isosteric and isoelectronic analogue of nicotinamide riboside, was prepared via the addition of a lithiated pyridine to 2,4 : 3,5-di-g-benzylidene-D-aldehydoribose, and subsequent cyclization.85 Syntheses of 3-chloro-4-( B D-ribofuranosy1)pyridine and of 3-(B-D-ribofuranosyl)-2-pyridone have also been reported.86 A paper on the analysis of pyridine

A

C-nucleosides is discussed in Chapter 22. The fluorinated C-nucleoside (45) is an isostere of the potent antiviral agent FMAU, and has been made from pseudouridine by standard methods. 87 When the tetrazole (46), prepared via cycloaddition of azide to the nitrile, was thermolysed in the presence of a dipolarophile, the nitrile imine produced in situ was trapped to give new heterocycles, 9. , the pyrazole (47) using dimethylacetylene dicarboxylate. 88 The C-nucleoside (48) has been prepared from 2-(B-D-ribofuranosy1)furan (Vol. 17, p.195), the key step involving the photooxygenation of a protected 2-amino-5- (B-D-ribofuranosyl)furan.89 Some peptide derivatives of the antitumour C-nucleoside tiazofurin have been reported, along with similar derivatives of ribavirin.90 The D-lyxopyranosylpyrroles (49) have been made by cyclization

212

Carbohydrate Chemistry 0

of the acyclic polyol, which in turn was synthesized by condensation of a 2-amino-2-deoxyheptose with methyl acetoacetate. 91 The synthesis of S-formycinyl-L-homocysteine was mentioned above.73 10 Carbocvclic Nucleoside Analoaues

Racemic carbocyclic analogues of purine nucleosides can be resolved using adenosine deaminase; thus, the 'D'-isomers of inosine and 2'deoxyguanosine were obtained, together with the IL'- forms of the . aminated substrates.92 Further examples of carbocyclic analogues of xylofuranosyl nucleosides have been reported (see Vol. 18, p.202), involving 2-amino-6- substituted purines and 8-azapurines as aglycones; some of the analogues showed antiviral activity. 93 The (+)-carbocyclic analogue of thymidine (50) has been prepared stereospecifically for the first time,as outlined in Scheme 14.9 4

Rcageds: b, (c~~~o),-M2SO4AcOH ; u, R e s m ( H + )

'r'

, L U ,MeOCH=C(Me]CONCO

OH

(50)

Scheme 14

(57)

OH

(52)

The intermediate (51), in racemic form, was used for the synthesis of various 2~-fluoro-carbocyclicnucleosides; the analogue' ( 5 2 ) of the important antiviral FMAU was prepared by introducing fluoride with inversion of configuration, whilst the compound of

20: Nucleosides

213

rib0 configuration was made by a double inversion sequence.

Oxid-

ation of (51) to a 2-ketone and then fluorination with DAST gave the 2 I , 2 I-difluoroanalogue of (52). 9 5 The optically-pure epoxide (53) prepared as indicated in Scheme 15, underwent regioselective ring opening to azidoalcohol (54), which was then used to prepare the fluoro-analogues (55) and (56)(X=H,I); the iodinated compounds are analogues of the antiviral IDU with the isosteric replacement of CHF for 0, and the 6'-a-fluorocompound (55, X=I) displayed good antiviral a~tivity.'~ Opening of epoxide (53) with the anions of uracil, thymine, or 2-amino-6-methoxyethoxypur~ne gave ultimately carbocyclic analogues of 2'-deoxynucleosides; the deoxyguanosine case is outlined in Scheme 15. The use of 2-amino-6-methoxyethoxypurine in epoxide openings was further illustrated by a synthesis of 97 carbocyclic guanosine, using a different epoxide. i,ii

H Oe'

OH 4 L,

~ L L ~ O , HV-O ( - ) * ; u , 6 ~ 8 r - N a H - B u q N I ; i i i ,

v, E5u3Snkt

;vi,

2-aminc-6-met~xypuLrine-LIY-DI?F ; L V , PhOCSCL;

H2-pd/& j v i i , 3 M lick

Scheme 15

The use of (+)-endo-5-norbornen-2-~1 acetate, obtained by enzymic resolution, has led to the synthesis of optically-pure (57),98 and similar chemistry, but involving an azide displacement, gave access to 3'-azid0-2',3~-dideoxythymidine (58) in opticallypure form. " The unsaturated carbocyclic compounds (59, B=Ad and Cyt), related to known anti-AIDS agents, were prepared by two consecutive deoxygenations of known compounds, but proved to be inactive. loo A range of carbocyclic analogues of 3 I-deoxypurine and -azapurine nucleosides of type (60) have been prepared and evaluated as antivirals. 101 A further report has appeared about the approach to carbocyclic C-nucleosides mentioned last year (Vol 20, p. 214), lo2 and this chemistry has been adapted to the synthesis of the carbocycle corresponding to oxazinomycin (61) (Scheme 16). 103

Carbohydrate Chemistry

214

(57)

(591

0 H N A O

Scheme

I6

11 Nuc1eosi.de phosphates and phosphonates new nucleoside diphosphosugar isolated from P.aeruginosa P1-I11 (Hals serotype 5) has been shown to have structure (62).Io4 Bis [2-(p-nitrophenyl)ethyl]phosphorochloridate has been further advocated as a new versatile phosphorylating agent,lo5 and it has been shown that the phosphorylation of nucleosides by phosphochloridates, pyrophosphates and triazolides is catalysed by sodium iodide, and, in the case of phosphorochloridates, by iodine.lo6 A

A

new general approach to nucleoside 3 ' - and 5'-phosphates involves formation of nucleoside diallyl phosphates, either by reaction with diallyl phosphorochloridate promoted by a Grignard reagent, or via oxidation of the phosphite; deprotection is then carried out with Pdo catalysis. 107 5'-g-Phosphatidyl nucleosides and deoxynucleosides have been made by enzymic transfer of the phosphatidyl unit from phosphatidyl choline,lo8 and the glucosyl phospholipid ( 6 3 ) of thyxqidine has been synthesized from glucose-6-phosphate, as a model for transmembrane

2 0: Nucleosides

215

transport: it was anticipated that hydrolysis of such compounds would give TMP. 109 Two routes have been reported to the 2-5A core structure, A2 'p5' A 2 'p5' A , llo'"ll and the analogous 3 I-deoxycompound, derived --from cordycepin, has also been synthesized,llZ as have phosphoro' 'I4 thioate analogues. Stec has reviewed, in a plenary lecture, the work of his group on the synthesis and absolute configuration at P-stereogenic centres The same in oligonucleotide triesters andd phosphorothioates. '15 group have reported a synthesis of (R )-thymidi11e-3'-[~~0, 170, 180] -P phosphate of diastereomeric purity > 9 2 % , and have prepared the (R )-and ( S )-diastereomers of thymidylyl (3'-5')-thymidylyl methane -P -P phosphonate as outlined in Scheme 17;l17 other workers have applied a similar approach to synthesize the corresponding methylphosphonothioates.'18

e.,

s

I

0

OH

Me+* (Separable)

sp fkagc%r&

i, M e P O t L p ; u.

6

-

0 NO*

p - n h v p h e n o L ; i, 310A~-My~rdcne

w

0 11l8.p-O-CH2

SP

OAc

S c h e m e 17

A review has appeared dealing with phosphonate analogues of biological phosphates, including analogues of nucleoside monoand higher phosphates. Some nucleoside methylene diphosphonate sugars, potential inhibitors of glycosyl transferases, have been reported,120 and an isosteric phosphonate analogue of CMP-KDO, the nucleoside phosphosugar involved in the incorporation of KDO into lipopolysaccharide, has been prepared and shown to be a modest inhibitor of CMP-KDO synthetase.12' Holy, in a plenary lecture, has discussed 2-phosphonomethyl analogues of nucleotides and their derivatives. 122

'''

:,","::

Two lariat trinucleotides, A: and A2 :p5 p51c lG , have been chemically synthesized. 12 3 Cyclic AMP analogues have been prepared from pyrazolo[3,4-d] pyrimidine nucleosides by DCC cyclization of the 5 '-phosphates,12* and a "P-n.m.r. study of the reaction of cyclic AMP with triisopropylbenzene sulphonyl chloride has shown the rapid formation of the three possible diastereomers (at phosphorus) of cyclic AMP

Carbohydrate Chemistry

216

symmetrical anhydride. 125 A mechanistic study of the formation of hydrogenphosphonate diesters during oligonucleotide synthesis, using acyl chlorides as coupling agents, has indicated the formation of mixed carboxylic-hydrogenphosphonic anhydrides as the main intermediates involved.126 Some further references to nucleoside derivatives of relevance to nucleotide synthesis are mentioned in the next two sections. 12 Ethers of nucleosides

Four 2'-g-methylated nucleosides have been isolated as components of the transfer RNA of extremely thermophilic archaebacteria; the structures, 5,2I -2-dimethylcytidine, N4-acetyl-2 I -2-methylcytidine, 2-thio-2 I -2-methyluridine and N2, y2-2 -g-trimethylguanosine, were confirmed by synthesis.127 A new method for the 2I-g-methylation of uridine derivatives, which does not require the protection of N3 of the uracil unit, is outlined in Scheme 18; this approach was used

k W

YSL-0

A

ReogenZ.5

L,

~

HO$

OH

OH OMe a 5 5 ) + a F i - Py , u ,Rnney N L ,UL

F-

(64)

Scheme 18

for a new synthesis of the methylated t-RNA constituent NHCH2C02H). 128

(64,

X=CH2

A method has been developed for the introduction of a dimethoxytrityl group at 0-5' of a nucleoside or nucleotide bound to a solid support via 0-3 I . 12' A series of 5 I-g-alkyl derivatives of 5-fluorouridine were prepared by standard coupling of the base to a 5-g-alkyl ribose derivative, but none of the products showed useful biological activity. 130 During a synthesis of N3-benzoylthymidine, the 3 ,5 -bis-gtrimethylsilyl ether of this compound was isolated as a solid precipitate after an aqueous work-up indicating that the trimethylsilyl derivative is more stable than was previously thought. 13'

13 Esters and acetals of nucleosides

Various 2-acyl derivatives of 2~-deoxy-5-trifluoromethyluridine and

2 0: Nucleosides

217

-cytidine have been synthesized and their antitumour activity examined to determine their potential as pro-drugs. 132 Similarly, a range of 5'-0- and 3-N-acylated derivatives of 5-(2-chloroethyl)-2'deoxyuridine have been prepared. 133 In a study of the partial protection of nucleosides, it was shown that acylation of a ribonucleoside with 1.2-1.5 equivalents of an acyl chloride in pyridine gave mostly the 2I-g-acyl isomer. Use of 2.2-3.0 equivalents of acyl chloride gave mostly the 2',5'-di-Oacyl derivative, which rearranged over silica to the 3',5'-diacyl nucleoside. The 2',5'- and 3',5'-di-g-acyl derivatives could be used to gain access to the 3'- and 2I-g-THP derivatives, respectively.134 Solid-liquid phase transfer conditions, involving formation of an intermediate dibutylstannylene derivative, have been developed for selective 2'-g-tosylation of ribonucleosides; 2'-g-tosyladenosine was obtained in 90% yield. 135 A new protecting group for 0-5' of nucleosides has been developed, particularly for use in solid phase oligonucleotide synthesis. This is the 2-(2,4-dinitrobenzenesulphenyloxymethyl)benzoyl (DNBSB) group (65), which is put on using the benzoic acid and pivaloyl chloride, and removed by a process of intramolecular catalysis using 50 mM toluenethiol and 200 mM diisopropylethylamine l3

.

A new approach, with an appropriate choice of protecting groups, has been developed for the synthesis of 2'(3')-g-aminoacyl oligoribonucleotides related to the 3 -terminus of aminoacyl t-RNAts,137 and 5'-g-aminoacyl derivatives of ribo- and arabinofuranosylnucleosides have been prepared. 138 A review of protection at the 2' position in oligoribonucleotide synthesis includes discussion of a number of acetal-type protecting groups, the lability of which has been carefully tailored to the other requirements of the overall syntheses.139 2'-0-(2Methoxy-2-propy1)acetals of type (66) have been prepared via the 3',5'-g-dialkylsilandiyl derivatives, and also used in oligonucleotide syntheses.140

Some new adenosine 2',3'-g-acetals have been prepared, and their

218

Carbohydrate Chemistry

stereochemistry and rates of hydrolysis determined. The compounds reported included those derived from hindered aldehydes, which gave predominantly endo -isomers, and the =-isomer of the 2',3'-g-methoxymethylidene orthoester was reported for the first time. The rates of hydrolysis were approximately as predicted, and were faster than depurination, except in the case of the exceptionally stable fluorenyl acetal (67), where the normal mechanism of hydrolysis would involve an antiaromatic cation.141 derivatives Various 3'- and 5'-mono-, and 3t,5'-di-O-alkoxyalkyl of 2~-deoxy-5-trifluoromethylurid~newere prepared by acetal exchange. Some showed improved antitumour activity due to suppression of metabolic degradation. 142 14 Reactions

By studying the effects of substitution at the 6-position of purine deoxynucleosides, further evidence has been obtained that the ratelimiting step in acid-catalysed hydrolysis is the departure of the protonated base moiety with concomitant formation of an oxocarbonium ion.143 The rate constants for acid hydrolysis of several N6substituted 2'-deoxyadenosines were measured in order to assess the role of various N6- and sugar-protecting groups in depurination reactions observed in oligonucleotide synthesis; the exceptional lability of N6-acyl derivatives can be accounted for by N7 protonation, as determined by I5N n.m.r. 144 Kinetic parameters have also been determined for the multistage reactions of 6-substituted purine nucleosides with alkali to give ultimately D-ribose and a 4,5-diaminopyrimidine. 145 The acidic hydrolysis of several carbon-bridged purine 5'-cyclonucleosides has been studied; a 5',8-bridged system hydrolyses less than 10 times more slowly than analogous nucleoside models, but 3 ,5(-bridgeslead to very substantial rate retardations. The results were rationalized in terms of electrostatic and 146 stereoelectronic effects. In connection with the postulated mechanism for DNA strand scission by activated bleomycin, the hydroperoxide (68) was produced as the major isomer as shown in Scheme 19. In aqueous buffer, this underwent a Criegee-type rearrangement to give ultimately the unsaturated aldehyde (69). On reduction with dimethylsulphide, (68) gave the ketoaldehyde (70), of relevance to the base-release also 147 observed in the reaction with activated bleomycin. It has been shown that in a 1:l mixture of GMP and the cis-

219

2 0: Nucleosides

n

J

OBz

R e ~ g e n t s L. , H ~ o ~ - T F A - T H F , u , D u F b o~)~; i~w(, Me25 ~H

S c h e m e 19

platin- like complex &-[Pt(NH3)2(H20)2] (CF3S0 ) a cyclic complex is formed involving coordination of Pt113t:'N7 of the base and to the phosphate group;148 a similar cyclic complex has also been demonstrated, by H ' n.m. r., in the interaction between AMP and 149 bis-cyclopentadienyl molybdenum dichloride in D20 at pD 7.6-7.8. Various macrocyclic polyammonium salts form stoichiometric complexes with ATP and ADP. I 5 O Protonation constants and stability constants 151 of Cu2+, Hg2+ and Pt2+ complexes of thymidine have been measured. The antitumour agent Ij2-methyl-9-hydroxyellipticinium acetate interacts with ribonucleoside diphosphates in a manner analogous to that previously determined for the nucleosides themselves (see Vols. 152 18-20, particularly vol. 19, p.209). 15 Spectroscopic and Conformational Studies

Theoretical calculations of conformational energies of adenosine have shown that E3-protonation is more favourable in the anticonfiguration than in the =-arrangement by 32.2 kcal mol,-' and that E 3 protonation may cause a change in conformation in adenosine derivatives. 153 Additionally, pH-dependent laser Raman spectroscopic studies of 8-bromo-AMP have indicated that a syn-conformation inhibits protonation at E 3 154 X-ray crystal structures of nucleosides are discussed in Chapter

.

22.

References 1

K. F e l c z a k , T . Kulikowski, J . A .

V i l p o , J. G i z i e w i c z , and D . Shugar, Nucleos i d e s N u c l e o t i d e s , 1987, 6, 257. D . J . McNamara and P.D. CoTk, J . Med. Chem., 1987, &, 340. I . P . Kupchevskaya and A.V. S t e t s e n k o , Ukr. Khim. Zh.(Russ. Ed.), 1986, 2 , 1087 (Chem. A b s t r . , 1987, 197, 217987). C . C r i s t e s c u , ,Rev. Roum. Chim., 1986, 3-1, 881 (Chem. A b s t r . , 1987, 1 0 7 , 115903).

I -

2 3

4

220 5 6 7 8

9 10

11 12 13 14

15 16 17

18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40

Carbohydrate Chemistry Y.S. Sanghvi, K.G. Upadhya, N.K. Dalley, R.K. Robins, and G.R. Revankar, - . Nucleosides Nucleotides,. 1987, 6, 737, C.-H. Kim and V.E. Marquez, J. O w . Cheq., 1987, 52, 1979. L. Kemps, E.L. Esmans, R. Dommisse, J.A. LepoivreTand F.C. Alderweireldt, Nucleosides Nucleotides, 1987, 5, 387. J. Andersen, E.S. Andreassen, and E.B. Petersen, Acta Chem. Scand., Ser. B., 1987, 41, 473. G.D. KT&, W.J. Hennen, and R.K. Robins, Nucleosides Nucleotides, 1987, 5, 581. G. Cristalli, P. Franchetti, M. Grifantini, S . Vittori, T. Bordoni, and C. Geroni, Nucleosides Nucleotides, 1987, 6 , 381. R. Zou and M.J. Robins, Can. J. Chem., 1987, 65, 1436. R. Noyori and M. Hayashi, Chem. Lett_., 1987, 57. Y.H. Kim, Stud. O w . Chem.(Amsterdam), 1986, 26, 211 (Chem. Abstr., 1987, --106, 214277). P. Goya, A. Martinez, M.L. Jimeno, and W. Pfleiderer, Nucleosides Nucleo-tides, 1987, 5, 375. P. Goya, A . Martinez,and C. Ochoa, Nucleosides Nucleotides, 1987, 6, 631. K. Ramasamy, R.K. Robins, and G.R. Revankar, J. Heterocycl. Chem., 1987, 5, 863. I.A. Korbukh, L.D. Garaeva, N.G. Yakunina, E.A. Kashutina, and M.N. Preobrazhenskaya, Bioorg. Khim., 1986, 12, 539 (Chem. Abstr., 1987, -106, . 67606). X. Wang, L. Dong, C. Xu, and S . Zhao, Beijing Yixueynan Xuebao, 1984, 323 (Chem. Abstr., 1987, 138718). G.R. Revankar, K. Ramasamy, and R.K. Robins, Nucleosides Nucleotides, 1987, 6, 261. N.S. Girgis, H.B. Cottam, S.B. Larson, and R.K. Robins, Nucleic Acids Res., 1987, 15, 1217 (Chem. Abstr., 1987, 107, 198829). N.S. G:ygis,H.B. Cottam, S.B. Larson=nd R.K. Robins, J. Heterocycl. Chem., 1987, 24, 821. J. Boryski and B. Golankiewicz, Nucleosides Nucleotides, 1987, 5, 385. G. Gosselin, M.-C. Bergogne, J. DeRudder, E. DeClercq, and J.-L. Imbach, J. Med, Chem., 1987, 30, 982. G. Gosselin, M.-C. Bergogne, J.-L. Imbach, J. DeRudder, and E. DeClercq, Nucleosides Nucleotides, 1987, 6, 65. A. Cuberta, M.L. Jimeno, and C. Ochoa, Nucleosides Nucleotides, 1987, 6, 831. P. Goya, A. Martinez, M.L. Jimeno, and W. Pfleiderer, Liebigs Ann. Chem., 1987, 961. I.P. Kupchevskaya, N.D. Mikhnovskaya, A.V. Stetsenko, and T.V. Yanishevskaya, Ukr. Khim. Zh.(Russ Ed,,), 1986, 52, 1085 (Chem. Abstr. 1937, 107, 217986). P. Drasar and J. Beranek, Collect. Czech. Chem. Commun., 1987, 52, 2070. K.W. Pankiewicz and K.A. Watanabe, Chem. Pharm. Bull., 1987, 357-4494. M. Sako, T. Saito, K. Kameyama, K. Hirota, and Y. Maki, Synthesis, 1987, 829. A.D. Shutalev, L.A. Ignatova, and B.V. Unkovskii, Khim. Geterotsikl. Soedi?. , 1986, 1652 (Chem. Abstr., 1987, 107, 217984). M. Ashwell, A.S. Jones, A. Kumar, J.R. Sayers, R.T. Walker, T. Sakuma, and E. DeClercq, Tetrahedron, 1987, 43, 4601, M. Sako, T. Saito, K. Kameyama, K. Hirota, and Y. Maki, J. Chem. SOC., Chem. Commun., 1987, 1298. R.D. Elliott, J.A. Montgomery, and J.M. Riordan, J. Org. Chem., 1987, 51, 2892, K. Hirota, Y. Kitade, T. Tomishi, and Y. Maki, J. Chem. So?., Chem. Commun., 1987, 1801. Y. Suzuki, A. Matsuda, and T. Ueda, Chem. Pharm. Bull., 1987, 35, 1085. Y. Suzuki, A. Matsuda, and T. Ueda, Chem. Pharm. Bull., 1987, 35, 1808. Y. Yoshimura, T. Sano, A. Matsuda, and T. Ueda, Nucleic Acids Symp. Ser., 1986, 17(Symp. Nucleic Acids Chem,, 14th, 1986) m h e m . Abstr., 1987, 127, 154654). G.B. Chheda, H.B. Patrzyc, A.K. Bhargava, P.F. Crain, S.K. Sethi, J.A. McCloskey, and S.P. Datta, Nucleosides Nucleotides, 1987, 6 , 597. H. Aoyama, Y. Kusayanagi, M. Yotsoji, I. Kitayama, T. Yamaguchi, and T. Kodama, Nippon Kagaku Kaishi, 1986, 1765 (Chem. Abstr., 1987, LOL, 176396).

106,

2,

20: Nucleosides 41 42 43 44 45 46 47 48 49 50 51 52

22 1

H. Aoyama, Bull. Chem. SOC. Jpn., 1987, 60, 2073. M. Bobek, I. Kavai, and E. DeClercq, J. Med.Chern., 1987, 2, 1494. H. Griengl, E. Wanek, W. Schwarz, W. Streicher, B. Rosenwirth, and E. De c1.ercq, J. Med. Chem., 1987, 30, 1199. C. Papageorgiou and C. Tamm, G l v . Chim. Acta, 1987, 2, 138. J. Ben--Hattarand J. Jiricny,-Nucleosides Nucleotides, 1987, 5, 393. F. Seela, H. Steker, H, Driller, and U. Bindig, Liebigs Ann. Chem., 1987, 15. H. Rosemeyer and F. Seela, J. Org. Chem., 1987, 52, 5136. F. Seela and W. Bourgeois, Heterocycles, 1987, 2, 1755. F. Seela, U. Bindig, H. Driller, W. Herderling, K. Kaiser, A. Kehne, H. Rosemeyer, and H. Steker, Nucleosides Nucleotides, 1987, 6, 11. G.E. Wright, C. Hildebrand, S. Freese, L.W. Dudycz,and Z. Kazimierczuk, J. Org. Chem., 1987, 52, 4617. Y.S. Sanahvi. N.B. Hanna. S.B. Larson, R.K. Robins-and G.R. Revankar, Nucleosides Nucleotides, 1987, $,- 761. C.-H. Kim, V.E. Marquez, S. Broder, H. Mitsuya, and J.S. Driscoll, J. Med. Chem.. 1987. 30. 862, n e r d e w i j n , J. Balzarini, E. DeClercq, R. Pauwels, M. Baba, S. Broder, and H. Vanderhaeghe, J. Med. Chem., 1987, 30, 1270. \ J.-C. Wu, H. Bazin, and J. Chattopadhyaya, Tetrahedron, 1987, 43,2355. T. Pathak and J. Chattopadhyaya, Tetrahedron, 1987, 4227. M. Berger, A. Shaw, J. Cadet, and J.R. Jones, Nucleosides Nucleotj.des, 1987, 6, 395. L.D. Nord, N.K. Dalley, P.A. McKernan, and R.K. Robins, J. Med. Chem., 1987, 30, 1044. L.M. Lerner, B. Sheid, and E. Gaetjens, J. Med. Chem., 1987, 30, 1521. M.M. Mansuri, I. Ghazzouli, M.S. Chen, H.G. Howell, P.R. Brodfuehrer, D.A. Benigni, and J.C. Martin, J. Med. Chem., 1987, 30, 867. P. Herdewijn, R. Pauwels, M. Baba, J. BalzariniTand E. DeClercq, J. Med. Chem., 1987, 32, 2131, K. Harada, J. Matulic-Adamic, R.W. Price, R.F. Schinazi, K.A. Watanabe, and J.J. Fox, J. Med. Chem., 1987, 2, 226. J.R. Mercer, E.E. Knaus, and L.I. Wiebe, J. Med. Chem., 1987, 30, 670. D. Bergstrom, E. Romo, and P. Shum, Nucleosides Nucleotides, 1987, 2, 53. K.W. Pankiewicz and K.A. Watanabe, Chem. Pharm. Bull., 1987, 35, 4498. T. Tsuji and K. Takenaka, Nucleosides Nucleotides, 1987, 5, 575. N.B. Dyatkina, A.A. Kraevskii, and A.V. Azhaev, Bioorg. Khim., 1986, 1048 (Chem. Abstr., 1987, 107, 78188). T.-S. Lin, M.S. Chen, C. McLaren, Y.-S. Gao, I. Ghazzouli, and W.H. Prusoff, J. Med. Chem., 1987, 30, 440. M.E. Perlman and K.A. Watanabe, Nucleosides Nucleotides, 1987, 6, 621. M. Kawana and H. Kuzuhara, Tetrahedron Lett., 1987, 2, 4075. J.A. Secrist 111, Nucleosides Nucleotides, 1987, 6, 73. R.D. Elliott, P.S. Pruett, R.W. Brockman, and J.A. Montgomery, J. Med. Chem., 1987, 30, 927. G. Cimino, A. Crispino, S. DeStefano, M. Gavagnin, and G. Sodano, Experientia, 1986, 42, 1301 (Chem. Abstr., 1987, 99640). P. Serafinowski, Synthesis, 1987, 879. L.N. Beigel'man, M. Ya. Karpeiskii, and S.N. Mikhailov, Bioorg. Khim., 1986, 12, 1359. (Chem. Abstr., 1987, 107, 176391). L.N. Beigelman, B. S. Ermolinsky,-d.V. Gurskaya, E.M. Tsapkina, M.Ya. Karpeisky, and S.N. Mikhailov, Carbohydr. Res., 1987, 166, 219. H. Hayakawa, H. Tanaka, N. Itoh, M. Nakajima, T. Miyasaka, K. Yamaguchi, and Y. Iitaka, Chem. Pharm. Bull., 1987, 35, 2605. A. Matsuda, K. Takenuki, H. Itoh, T. Sasaki, and T. Ueda, Chem. Pharm. Bull., 1987. 35. 3967. L.H. 'KGle, H.M. Buck, H. Bazin, and J. Chattopadhyaya, Tetrahedron, 1987, 43, 2989. H. Bazin and J. Chattopadhyaya, -Chem. Scr., 1986, 26, 13 (Chem. Abstr., 1987, 106, 156804). M. Ashwell, A.S. Jones, and R.T. Walker, Nucleic Acids Res., 1987, I . , 2157 (Chem. Abstr., 1987, 107, 154665). -

-

I

*

*

53 54 55 56 57 58 59 60

61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80

,

5,

-

12,

106,

222

Carbohydrate Chemistry

81 M. Suzuki, H. Tanaka, and T. Miyasaka, Chem. Pharm. Bull., 1987, _3_1, 4056. 82 M. Kawana, I;. Takeuchi, T. Ohba, and H. Kuzuhara, PJucIeic Acid Symp. Ser., 1986, 17(Symp. Nucleic Acids Chem., 14th, 1986) 37 (Chem. Abstr., 1987,107, 97040). 83 J . A . Maurins, R.A. Paegle, 14.5. Lidaks, E.I. Kvasyuk, and I.A. Mikhailopulo, Bioorg. Khim., 1986, 12, 1514(Chem. Abstr., 1987, 107, 176394). 34 K.A. IJatanabe, Yuki Gixei Kagaku Kyokaishi, 1987, 212 (?hem. Abstr., 1987, 107_, 198764). 85 M.M. Kabat, K.W. Pankiewicz, and K.A. Watanabe, J. Med. Chem., 1987, 30, 924. 86 M. Belmans, I. Vrijens, E.L. Esmans, J.A. Lepoivre, F.C. Alderweireldt, L.L. Motring, and L.B. Townsend, Nucleosides Nucleotides, 1987, 5, 245. 87 K.W. Pankiewicz, B. Nawrot, H. Gadler, R.W. Price, and K.A. Watanabe, J . Med. Chem., 1987, 30, 2314. 88 J. Kobe, M. Prhavc, M. Hohnjec, and L.B. Townsend, Nucleosides Nucleotides, 1987, 6, 365. 89 I. Maeba, 0 . Hara, M. Sukuki, and H. Furukawa, J . Org. Chem., 1987, 52, 2368. 90 K. Ramasamy, G.D. Kini, R.K. Robins, and G.P. Revankar, Nucleosides Nucleotides, 1987, 6, 901. 91 J . A . Galbis Perez, E. Roman Galan, M.A. Arevalo Arevalo, and F. Polo Corrales, An. Quim., Ser. C, 1986, 82, 76 (Chem. Abstr., 1987, >>6-, 176786). 92 J.A. Secrist 111, J.A. Montgomery, Y.F. Shealy, C.A. O'Dell, and S.J. Clayton, J. Med. Chem., 1987, 30, 746. 93 R. Vince, R.H. Turakhia, 1J.M. Shannon, and G. Arnett, J. Med. Chem., 1987, 30, 2026. 94 L. Utvbs, J. Beres, G. Sagi, I. TUmBskUsi, and L. Gruber, Tetrahedron Lett., 1987, 8, 6381. 95 K. Biggadike, A.D. Borthwick, D. Evans, A.M. Exall, B.E. Kirk, S.M. Roberts, L. Stephenson, P. Youds, A.M.Z. Slawin, and D . J . Williams, J. Chem. SOC., Chem. Commun., 1987, 251. 96 K. Biggadike, A.D. Borthwick, A.M. Exall, B.E. Kirk, S.M. Roberts, P. Youds, A.M.Z. Slawin, and D.J. Williams, J. Chem. SOC., Chem. Commun., 1987, 255. 97 K. Biggadike, A.D. Borthwick, A.M. Exall, B.E. Kirk, S. M. Roberts, and P. Youds, J. Chem. SOC., Chem. Commun., 1987, 1083. 98 M. Bodenteich, K. Faber, G. Penn, and H. Griengl, Nucleosides Nucleotides-, 1987, 6, 233. 99 M. BodTnteich and H. Griengl, Tetrahedron Lett. , 1987, Lg, 5311. 100 V.E. Marquez, C.K.H. Tseng, S.P. Treanor, and J . S . Driscoll, Nucleosides Nucleotides, 1987, 6, 239. 101 Y.F. Shealy, C.A. OTDell, and G. Arnett, J . Med. Chem. , 1987, 30, 1090. 102 N. Katagiri, T. Haneda, S . Tomizawa, and C. Kaneko, Nucleic Acids Symp. Ser., 1986, 17(Symp. Nucleic Acids Chem., 14th, 1986), 1 (them. Abstr., 1987,,-78194). 103 N. Katagiri, M . Tomura, T. Haneda, and C. Kaneko, J. Chem. SOC., Cornmun., 1987, 1422, 104 K O k u d a , S. Murata, and N. Suzuki, Biochem. J., 1986, 239, 733 (Chem. Absty., 1937, 106, 1934). 105 F. HiGXsbach, R. Charubala, and W. Pfleiderer, Helv. Chim. Acta, 1987, 70, 1286. 106 f&, Strumberg and J. Stawinski, Nucleosides Nucleotides, 1987, 6, 815. 107 Y . Hayakawa, S. Wakabayashi, T. Nobori, and R. Noyori, Tetrahedron Let:., 1987, 28, 2259. S. Ueda, S. Imamura, K. Fukukawa, A. Matsuda, and T. Ueda, Tetra108 S . Shu-t;, hedron Lett., 1987, 2 2 , 199. 109 r.1. Guerra, J.M. Neumann, and T. Huynh-Dinh, Tetrahedron Lett-., 1987, _2_8_, 354l. 110 K. Kamaike, S. Yamakage, and Y. Ishido, Nucleosides Nucleotides, 1987, 5 , 841. 111 E.1. Kvasyuk, T.A. Kulak, N.B. Khripach, I.A. Mikhailopulo, E. Uhlmann, R. Charubala, and W. Pfleiderer, Synthesis, 1987, 535.

5

e.

--

112 R. Charubala, E. Uhlmann, F. Himmelsbach, and W. Pfleiderer, Helv. Chi?. Acta, 1987, 70, 2028.

2 0: Nucleosides 113

114 115

116 117 118 119 120 121 122 123 124 125 126 127 128

223

R. Charubala and W. Pfleiderer, Nucleosides Nucleotides, 1987, 5, 513. K. Kariko, S.W. Li, R.W. Sobol Jr., L. Suhadolnik, N.L. Reichenbach, R.J. Suhadolnik, R. Charubala, and W. Pfleiderer, Nucleosides Nucleosides, 1987, 6, 173. P. Guga, M. Koziolkiewicz, A. Okrusek, B. Uznanski, and W.J. Stec, Nucleosides Nucleotides, 1987, 6, 111. A. Okruszek, P. Guga, and W.J. Stec, J. Chem. Soc., Chem. Commun., 1987, 594. Z.J. Lesnikowski, P.J. Wolkanin, and W.J. Stec, Tetrahedron Let;., 1987, 2 8 , 5535. W.K.-D. Brill and M.H. Carruthers, Tetrahedron Lett., 1987, 28, 3205. G.M. Blackburn, G.E. Taylor, R.H. Tattershall, G.R.J. Thatch=, and A. McLennan, Bioact. Mol., 1V07, 3(Biophosphates Their Analogues) , 451 Abstr., 1987, 107, 23712b). M.M. Vaghefi, R . J . Bernacki, W.J. Hennen, and R . K . Robins, J. Med. Chem. , 1987, 30, 1391. D.W. Nzbeck, J.B. Kramer, and P . A . Lartey, J . Org. Chem., 1987, 52, 2174. A. Holy, Nucleosides Nucleotides, 1987, 5, 147. J.-M. Vial, N. Balgobin, G. Remaud, A. Nyilas, and J. Chattopadhyaya, Nucleosides Nucleotides, 1987, 5, 209. LDAnderson, R.K. Robins, and G.R. Revankar, Nucleosides Nucleotides, 1987, 6, 853. J. Tomasz, S. Bottka, and I. Pelczer, Nucleosides Nucleotides, 1987, 5, 785. P.J. Garegg, T. Regberg, J. Stawinski, and R. StrTJmberg,eosides Nucleotides, 1987, 2, 655. C.G. Edmonds. P.F. Crain. T. Hashizume, R. Gupta, K.O. Stetter, and J.A. McCloskey, J: Chem. Soc.; Chem. Commun:, 1987; 969. M. Sekine, L.S. Peshakova, T. Hata, S. Yokoyama, and T. Miyazawa, J. Org. Chem.. 1987. 52. 5060. M.P. Reddy, JZ. Rampal, and S.L. Beaugage, Tetrahedron Lett,, 1987, 28, 23. A. Holy, J . K h i g , 3 . Vesely, D. Cech, I, Votruba, and E. DeClercq, Collect. Czech. Chem. Commun., 1987, 52, 1589. M. Sekine, M. Fujii, H. Nagai, and T. Hata, Synthesis, 1937, 1119. J. Yamashita, S. Takeda, H. Matsumoto, T. Terada, N. Unemi, and M. Yasumoto, Chem. Pharm. Bull., 1987, 35, 2090. H. Griennl. W. Schwarz, F. Schatz, M. Skrobal, G, Werner, and B. Rosenwirth, --Chem. Scr., 1986, 26, 67 (Chem. Abstr., 1987,-=, 59385). K. Kamaike, F. Uemura, S. Yamakage, S. Nishino, and Y. Ishido, _Nucleosides Nucleotides, 1987, 4, 699. A. Grouiller, H. Essadiq, B. Najib, and P. Molikre, Synthesis, 1987, 1121. C.Christodoulou, S.Agrawa1, and M.J.Gait, Nucleosides Nucleotides, 1987, 6, 341 C. Scalfi-Happ, E.Happ, and S.Chladek, Nucleosides Nucleotides, 1987,6, 345. G.H. Hakimelahi, M. Zarrinehzad, A.A. Jarrahpour, and H. Sharghi, Helv. Chim. Acta, 1987, 2, 219. C.B. Reese, Nucleosides Nucleotides 1987, 6, 121. H. Takaku, K. Imai, and KChem. Kett., 1987, 1787. V. Bakthavachalam, L.-G. Lin, X.M. C h w A.W. Czarnik, Carbohydr. Res., 1987, 170, 124. J. Yamashita, S. Takeda, H. Matsumoto, N. Unemi, and M. Yasumoto, Pharm. Bull., 1987, 35, 2373. M. Oivanen, H. LUnnberg, X. Zhou, and J. Chattopadhyaya, Tetrahedron, 1987, 43, 1133, -G. Remaud, X.-X. Zhou, J. Chattopadhyaya, M. Oivanen, and H. Ltinnberg, Tetrahedron, 1987, 43, 4453. H. Lhnberg, R. KNpZ, P. Lehikoinen, and M. Oivanen, Acta Chem. Scand., Ser. B., 1987, 41, 34. L.-G. Lin, V. Bzthavachalam, X.M. Cherian, and A.W. Czarnik, J. Org. Chem. 1987.- 52., 3113. I. S a i z , T. Morii, and T. Matsuura, J. Org. Chem., 1987, 52, 1008. M.Green and J.M.Miller, J. Chem. SOC., Chem. Commun., 198751-1864. L.Y.Kuo, M.G. KanatzidiS and T.J. Marks, J.Am.Chem.Soc., 1987, 109, 7207. M.W. Hosseini and J.-M. Lehn, Helv. Chim. Acta, 1987, 70, 1312.

(s.

~~

129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150

I

-

_

m.

224 151 152

153 154

Carbohydrate Chemistry R. M'Boungou, M. Petit-Ramel, G . Thomas-David, G. Perichet, and B.Pouyet,

Can. J. Chem., 1987, 65, 1479. T.B. Tam Ha, J. Bernadou, and B. Meunier, Nucleosides Nucleotides,l987, 691, G.A. Walker, S.C. Bhatia, and J.H. Hall, Jr., J. Am. Chem. SOC., 1987, 7629. G.A.Walker, S.C.Bhatia, and J.H.Hal1, Jr., J.Am.Chem.Soc., 1987, 109, 7634.

5, 109,

21 N.M.R. Spectroscopy and Conformational Features

1

'Theoretical and General Considerations

A description of

13

C-n.1n.r. simulation methodology for the struct1 ural elucidation of carbohydrates has appeared. Some long-range 'C-'d coupling constants have been determined in carbohyarate derivatives by 2U-n.1n.r. techniques on the natural abundance compounds. The values obtained were found to compare well with 2 values from the selectively isotopically enriched ( I 3C o r 14) 2 carbohydrates previously reported. A simple procedure to simplify 1 1 the 21) H- fi (2D COSY) spectra of molecules in which significant

'1' variations occur has been described and used to distinguish 1 3 between methine and methyleae protons of L-idose. An interesting new observation is that axial anomers induce an 0(5)-C(l)-O angle greater than tetrahedral, whereas for the equatorial anomers the reverse is true. The observation was rationalized on the 4 The effects of solvent polarity and hydrogen basis of 140 analysis. bond L'orrnation on the magnitude of the anorneric effect has been 13 studied using a C-n.rn.r. method, and the results interpreted in terins of solvent interactions causing changes in the endo- and e z anomeric effects. hater strengthens the zo-anoineric effect and the conforlnational rigidity o f glycosides because of its Il-londinG to the ring oxygen atom. The tendency of free sugars to favour an equatorial hydroxy group, it is suggested, is in part due to the 5 ability to form stronger hydro6en bonds as proton donors. 1 Unsaturated sugar derivatives have been studied by 1 3 C - and d n.m.r. spectroscopy to examine the generalized anomeric effect, 5 particularly with regard to the allylic effect. The importance of antiperiplanar n-ff-" stabilization as a contributor to the ano-

226

Carbohydrate Chemistry

m e r i c e f f e c t h a s b e e n c o n f i r u e d by v a r i a b l e t e m p e r a t u r e

1

ti- a n d I 3 C a n d 2-substituted-4-uethyl-tetra7 1 l i y d r o p y r a n s o f t h e t y p e s shown i n f o r m u l a ( 1 ) . uy rneans of rl

r1.m.r.

s t u d i e s on 2 - s u b s t i t u t e d -

n.1n.r.

s t u d i e s of Z , 4 - d i s u b s t i t u t e d - ~ - c ~ r b a 1 n o ~ l - 5 , 6 - ~ i h y d r o - ~ ~ - ~ y r a

t h e conf o r m a t i o n a l p r e f e r e n c e and hence t h e r e v e r s e ariomeric e f f e c t or‘ t h e c a r b a m o y l g r o u p n a s b e e n d e t e r m i n e d .

b

The d e t e c t i a n o f t h e s i x t a u t o r n e r s o f b - g l u c o s e 13 C-n.1n.r. i s r e f z r r e d t o i n Chapter 2.

s o l u t i o n by

assignment of t h e

13

C-n.m.r.

ill

aqueous ‘I’he c o n p l e t e

spectrum of t h e r i n g forms of d i g i t -

O X O S ~ (2,b-dideoxy-U-ribo-nexose)

-

by U%F”I’ e d i t i n g and 20 C - d

c o r r e l a t i o n s p e c t r o s c o p y h a s been r e p o r t e d .

The a r i o m e r i c p a i r s o f

t n e f u r a n o s e a n d pjranose f o r i n s i t e r e q u a n t i t a t i v e l y a n a l y z e d i n uiV1SO-d

s o l u t i o n by b 1 t n o s e f r o m d-n.7n.r.

l’orms o f 0 - f r u c t o s e

13

C-n.711.r.

a n a t h e r e s u l t s compared w i t h

spactroscopy.’

hxamination of t n e r i n g

a n d t h e e f f e c t s of tL-bonding

e q u i l i b r i u i n i s r e f e r r e d t o i n Chapter 2, and t h e

t h e g o s i t i o n of 13 C-n.5.r.

011

s p e c t r o s c o p i c determiriation 02 t h e r i n g s i z e s of isoproi3ylidene d c e t a l s i s i l i e n t i o n e d i n C h a p t e r 6.

‘i’he (i;

1

tL-n.ru.r.

-G

L

)

spectroscopj

01’

a r a n g e of b e n z o y l a t e d polyrols

nave been d e s c r i b e d and t h e i r p r o b a b l e conformations i n

O

solution discussea.

10

siiililar s t u d i e s of s o m benzoyidted aldono-

r i i t r i l e s and p o l y L e n z o y 1 d l d i t o i d e r i v a t i v e s o f t e t r a z o l e s h a v e been 11 , I d C d r r l e d o u t by t i l e salne g r o u p . ‘ i h e c o n f o r i n a t i o n o f 1,l-bis(acetamid0)-I-deoxy-0-glucitol 1

u e e n d e t e r m i n e d i n a q u e o u s s o l u t i o n f r o m >UC) i h i z

ti-n.5.r.

has data.

No

a i f f e r e n c e f r o m t h a t d e t e r m i n e d p r e v i o u s l y i n o r g a n i c s o l u t i o n s was

fourid

.13

3

-Ab i n i t i o

Furanose S y s t e ~ inolecular o r b i t a l c a l c u l a t i o n s have been a p p l i e d t o

e r i t h r o f u r a n o s e and threofuranose.

‘Ihe p r e f e r r e d s o l u t i o n conform-

a t i o n s a s c e r t a i n e d p r e v i o u s l y by r1.m.r.

s p e c t r o s c o p y a r e i n good

a g r e e m e n t w i t h t h o s e p r e d i c t e d by c a l c u l a t i o n a n d , i n c o n t r a s t t o t h f i n d i n g s i n r e f e r e n c e 5 a b o v e , i t was i n f e r r e d t h a t s o l v a t i o n b d a t e r d o e s n o t a p p e a r t o be a major c o n f o r m a t i o n a l d e t e r u i n a i i t .

3;4

‘the c o n f o r m a t i o n s i n s o l u t i o n of b o t h anoiners of $-benzoyl-D-gluco1 15 i u r a n o s y l a m i n e n a v e b e e n d e t e r m i n e d b j H-n.m.r. spectroscopy.

227

21: N . M . R . Spectroscopy and Conformational Features A 500

m z v a r i a b l e t e m p e r a t u r e 'H-n.m.r.

s t u d y o f 9-(2'-deoxy-/-D-

t , e o - p e n t o f u r a n o s y 1 ) a d e n i n e and i t s 3I-deoxy isomer h a s been 16 carried out. The c o n f o r m a t i o n s i n s o l u t i o n o f a number o f a l d o n o - 1 , ! + - l a c t o n e s 1 1 w i t h 1 3 C - e n r i c h ~ n e n t a t C-I h a v e b e e n e v a l u a t e d u s i n g H- FI, 13 1 1 3 13 17 C- ti, a n d CC - c o u p l i n g s i n t h e i r n.m.r. s p e c t r a .

4

Pyranose Systems

'The a n t i c i p a t e d h a l f - c h a i r c o n f o r u i a t i o n s o f t h e f o u r b e n x y l 2 , 3 anhydro-4-azido-4-deoxy-pentopyranosides h a v e b e e n c o n f i r m e d by 18 1 3J v a l u e s i n t h e i r 14-n.rn.r. spectra. The c o n f o r m a t i o n a l a n a l y s i s o f t h e two d i a s t e r e o i s o m e r s o f t h e p e n t o s e o r t h o - e s t e r ( 2 ) 19 h a s b e e n a c h i e v e d by d e t a i l e d n . m . r . s t u d i e s .

1

d-N.m.r.

s t u d i e s o f g l u c o s e , m a l t o s e a n d some d e r i v a t i v e s i n

- 3-OH h y d r o g e n b o n d i n g i n m a l t o s e , and r e v e a l weaker i n t r a m o l e c u l a r hydrogen bonding between DivISO c o n f i r m t h e p r e s e n c e o f 2 ' - O k I

v i c i n a l hydroxy groups. Cooperative intramolecular h drogen bonding 20 13 i n g l u c o s e was a l s o e s t a b l i s h e d . The s o l i d s t a t e C-n.m.r. s p e c t r u m o f a s i n g l e c r y s t a l o f methyl A-D-glucopyranoside h a s been s t u d i e d and u s e d t o a s s i g n t h e c.p.-m.a.s. spactruln o f a p o l y c r y s t a l 21 1 13 l i n e sample. A c o n p a r a t i v e s t u d y o f t h e d- a n d C- n . m . r . s p e c t r a o f a l l m o n o a c e t a t e s o f m e t h y l d- a n d / 3 - D - g l u c o p y r a n o s i d e of 0-glucose

and D-galactose

and

w i t h t h o s e of t h e i r u n a c e t y l a t e d d e r i v -

a t i v e s h a s shown a s t r o n g d e p e n d e n c e o f t h e s i g n a l s o n t h e p r e s e n c e of a x i a l s u b s t i t u e n t s , a s w e l l a s p r o v i d i n g d a t a f o r d e t e r m i n i n g t h e 22 o r i e n t a t i o n of t h e e s t e r groups. A comprehensive a n a l y s i s of t h e 1 13 H- a n d C-n.m.r. d a t a f o r t h e a n o i n e r i c p a i r s o f a L o , manno, a n d t a l o i s o m e r s o f m e t h y l 2,3-anhydro-f+,6-Q-benzylidene-D-aldohexop y r a n o s i d e s u s i n g 2D homo- a n d h e t e r o - c o r r e l a t i o n t e c h n i q u e s h a s b e e n r e p o r t e d . 23 b e e n s t u d i e d by

1

C h i r a l l y d e u t e r a t e d g a l a c t o s e d e r i v a t i v e s have H-n.m.r.

s t a t e a b o u t t h e C-5

-

C-6

spectroscopy and t h e p r e f e r r e d rotameric bond shown t o b e gt.

Ivlethylp-D-galacto-

p y r a n o s i d e s s p e c i f i c a l l y d e u t e r a t e d a t C-6 w e r e u s e d t o show t h a t a D-galactose

oxidase a c t e d mainly a t t h e

c o i n p a r i s o n of

3C

spin-lattice

pro-(S)

hydrogen.24

A

r e l a x a t i o n t i m e s between s u g a r s of

Carbohydrate Chemistry

228

the D-gluco- and -galacto-series has been reported. The C-b methylene protons were hardly discernable for D-galactoses, but were clearly distinguished for the D-glucoses. The different rotational patterns were attributed to avoidance of the diaxial 0-4 - 0-6 25 . interactions which occur in galactose but not in glucose. datersoluble spin labelled glucose derivatives as potential n.m.r. contrast enhancing agents have been prepared, the compounds, which contain various nitroxyl radical substituents attached via 0-1, 2 - 2 , 0 - 3 , or 0 - 6 , produced marked enhancements of T and T proton 26 1 2 relaxation times. solution conformations of 3 , 4 , 6 - t r i - Q - a c e t y l - I , 2 - O - i s o p r o p r o p y l i d e n e d-D-galactopyranose have been compared with those of the solid obtained by &-ray crystallography and shown to be very similar, with the conformation of tLie pyranose ring being the expected 4C and c-1 27 -1 the dioxalan h. A series of specifically deuterated d- and p-C-glucopyranosides, 1 studied by H-n.m.r. spectroscopy, were shown to adopt analogous 28 1 conformations to the Corresponding 2-glycosides. Detailed 6-, I 3 C - , and 19F-n.m.r. spectroscopic data for inethyl d- ana p - g l y c osides of 2-fluoro and 3-fluoro-glucose, whose synthesis is described in Chapter 8, has been reported, together with those for their synthetic The conforuational equilibrium of 2,4,6-tri0-benao~l-3-deoxy-D-arabino-hexono-1,j-lactone has been examined b 1 36 means of coupling constants obtained from the i-l n.m.r. spectrum. k complete set of interproton-coupling data on w-l-idopyranosyluronic acid has been obtained in a high Yield n.m.r. study. The data indicate that o(-L-iduronic acid may display considerable conformat1 2 31 4C and _S conformers. ional freedom including C -4’ - 1 ’ rcotamer populations around C-3 - C-6 bonds of methyl 2,j,b-tri-guethyi-&- and -p-D-galactopyranoside 6-(dimethylphosphate) in 1 different solvents have been determined by H-n.m.r. spectroscopy; dome were shown to be solvent dependent while others were not. 1n1iL)O calculations on model systems correlated well with the n.m.r. 32 measurements in carbon tetrachloride. ‘The conformation of

intermediate^.^^

21 :N . M .R . Spectroscopy and Conformational Features

229

2,~,4,b-tetra-~-acetyl-l~-acetyl-~-~-~alactopyranosylamine has been

1determined by 500 MHz 6-n.rn.r. spectroscopy and found to be similar to that in organic s01vents.l~ Glycopeptides ( 3 ) and ( 4 ) , which have immunomodulatory and other biological activity, have 1 been studied by 2D J n.m.r. spectroscopy at 500 IvlHx and some 2U Flethods have been used to conformational conclusions drawn.3' values for conformationally rigid compounds such determine 3J as (5) and (gfHand the validity of the Karplus relationships examined. It was concluded that ring substituents can cause 34 deviations. piethyl glycosides of ammonium 3-deoxy-D-manno-2-octulosonate 1 conformation from i n.m.r. ( K W ) have been shown to adopt the 'C data by two different groups of workers. -2 j 5 9 j 6 Conformations o f the side chain of 1-acetylneuraminic acid and some of its e imers 1 13 37 C-n.m'.r. and n.0.e techniques. have been studied by 13-,

5

Oligosacchariaes and Kelated Compounds

An r1.m.r. technique, based on coherence transfer in the rotating frame, Mhich allows Tor the rapid determination of proton resonance assignments in oligosaccharides has been described.jb Improved 1 one-dimensional analysis of complicated ii-n.m.r. spectra of oligosaccharides has been achieved by a new technique which uses multiple relay uagnetization transfers. The analysis allows the visualization of each sugar unit on its own by multiple relay transfer from the anomeric protons .39 The carboiiyl resonances in peracetylated Dgluco- and D-manno-pyranosides and in oligosaccharides containing D&lucopyranose residues have been assigned using 2D n.m.r. techniques. it was proposed that the carbonyl carbon resonances are useful probes of 0ligosacchari.de str~cture.~' A study of virtual and solution conformations of oligosaccharides has led to a quantitative evaluation of the possibility that n.0.e. and bulk longitudinal relaxation tiaes, used to determine solution conformation of oligosaccharides, may be the result of averaging over many conformational states. 41 b l o d e l trimethylsilylated x lo-oiigosaccharides 15 j; 1 C m.a. s. n . m . r . , and I-i-"Si and Hhave been examined by 13i: heteronuclear correlation using 2D 6 techniques to assign the Geaks. It was concluded that the silicon 6 values can be used to 42-44 cietermine the sites of glycosidation. Gonlormational analysis of methyl ,!+-g-(d- a n d / 3 - U - g l u c o p y r a n o s j . l ) P-0-xylopyranoside in aqueous solutions has been carried out using

230

Carbohydrate Chemistry

n.0.e.

e f f e c t s f o r h y d r o g e n a n d c a r b o n a t o m s a d j a c e u t t o t h e glyco-

s i d i c bond t o g e t h e r w i t h o p t i c a l r o t a t i o n m e a s u r e m e n t s .

u - a c e t y l d e r i v a t i v e s of a l l ( 1 + j ) - a n d ( 1 - 4 ) - l i n k e d s a c c h a r i d e s , as w e l l a s inethyl tetra-2-acetyl-A-

45

The p e r -

galactose di-

and -p-D-galacto-

; J j r a n o s i d e a n d 1,1,4,o-tetra-i)-acetyl-j-l)-raethyl- a:id 1 , 1 , 3 , 6 - t e t r a -

-u - a c e t y . l - 4 - ~ - m e t h y l - c ~ - D - g a l a c t o p y r a l ? o s e 1i.m.r.

analysis achieved.

4b

T:le

c o n f o r m a t i o n s a d o p t e d by t h e < ; - g l y c o s i d i c

a n d ( 8 ), t h e c - a n a l o g u e s

a i s a c c h a r i d e s ('/)

and methyl d - g e n t i o b i o s i d e n.1n.r.

h a v e b e e n e x a m i n e d by 21)

h e t e r o n u c l e a r c o r r e l a t i o n s h i f t e x p e r i m e n t s , and a complete

respectively,

of illethyl oc-isomaltoside

h a v e b e e n d e t e r m i n e d by

1

11-

s t u d i e s of t h e i r s p e c i f i c a l l y d e u t e r a t e d methylene analogues.

The Same l a b o r a t o r y . h a s d e s c r i b e d s i m i l a r s t u d i e s o n e i g h t I,&-C;-

48

linked disaccharides. 13C-Lq.rn.r. i n v e s t i d a t i o n of cellobiose 1 u s i n , ; T i n e t h o u s i n t h e p r e s e n c e a n d a b s e n c e o f 4 - g l u c o s i d a s e shows

HO

OH

OH

OH (8)

(7)

a f a s t i n t e r a c t i o n b e t w e e n c e i i o b i o s a a n d t h e enzyme w i t n t h e I;-1 f o r u of the disaccharide.

'The 'I'

d a t a j u s t i f y a nearly. s p h e r i c a l

149

shape f o r c e l l o b i o s e i n s o l u t i o n . iviultiple-relayed

coherence t r a n s f e r cheiaical s h i f t - c o r r * l a t e d

1

id-

5u

n.m.r.

spectroscopy has been a p p l i e d t o cello-oligosaccharides. 1 13 C-n.m.r. s p e c t r a o f t o b r a r n y c i n ( 9 ) a t A s s i g n m e n t s of t h e 14- a n d

l o w a n d h i g h pH h a s b e e n a c h i e v e d by u s e o f 21, m e t h o d s .

The r e s u l t s

v e r e c o n s i s t e n t w i t h a C'

conforuation f o r each r i n g , independent '1 51 of the s t a t e of protonation.

h o d e r n n . rm. r . t e c h n i q u e s ,

i n c l u d i n g i-inQG,

rih

C, a n d

d c ) k i ~ H Ap u l s e

sequences, have been a p p l i e d t o t h e a n a l y s i s of t h e Injz 11.m.r. s p e c t r a o f A-neu 5~~-(2+j)-@-tial-(1+4)-Glc. A

c o u b i n a t i o n o f n.m.r.

and I3C-

t e c h n i q u e s a n d HSLA c a l c u l a t i o n s h a s b e e n

a p p l i e a t o t h e conformational a n a l y s i s of t h e following t e t r a s a c c -

-

h a r i d e s : GU-lvianp- ( 1 + 3 ) - [d-ll-ld~anr- ( 1-61 1 -4-aeoxy-B -D-lyx-hexg-

-

( 1+ 4 )

23 1

21: N . M . R . Spectroscopy and Conformational Features D-GlciJkc

, Li'-l)-i4anp-

( 1 +3 ) - Ld-D-Pianp- ( 1 - 0 )

1 -$-g-Tale-

1 ,o-anhydro-~-L)-tilciJAc

t h e corresponding

( 1-4) -i)-tilcNAc

[%-O-i4anp- ( I -w) J -/J-W-lianp-- ( 1 - 4 ) -1 ,6-anhydro-~-L)-CrlcllAc,

( 1 +j)- Ld-O-Aanp- ( 1 -b) 1 -4-deoxg-,3-U-&/x-hexpLr1ciiric .'3

and

d e r i v s t i v e , d-U-,Jlanp ( 1 dj)( 1 - 4 ) -1

arid oc-lJ-nant-

,o - a I i h j d r O - ~ - U -

' t h e - n . m . r. a p e c t r u r n o f 6-O-a-U-~iuco~yranosylcyclomdlto-

h e x a o s e h a s b e e n a r i a l y z e d employia;; f i l t e r e d COSY t e c h n i q u e s . 5 4 hexaose,

-hepT;aose,

phase s e n s i t i v e d o u b l e quantum

'l'ne n j a r d t e d a n d a n h y d r o u s c y c l o i n a l t o -

and -octaose

c y c l o d e x t r i n s have been i n v e s t i g a t e d

by solid s t a t e c r o s s p o l a r i a a t i o r i - d i p o l a r d e c o u p l i n k m a L i c - a n g l e 13 5> spinnins i;-n.m.r. spectroscopy. 'i'he i n f l u e n c e o f n o n - a q u e o u s Dlood group oligosaccharides

n.m.r.

and c.d.;

s o l v e n t s on t h e c o n f o r I n a t i o n s o f

h a s b e e n s t u d i e d by a p p l i c a t i o n o f

t h e y w a r e f o u n d t o b e e s s e n t i a l l y i d e n t i c a l i n DPISU

a n d O 0 , a n d v e r y s i m i l a r i n p y r i d i n e for t h e d l o o d g r o u p A t e t r a -

2

saccharide,

c o n s i s t e n t w i t h t h e p r o p o s a l t h a t non-bonded

doininate t h e c o n f o r u a t i o n s . 5 6

interactions

'The s u g a r r e s i d u e s i n a n u n b e r o f

g e r a c e t y l a t e d g l y c o s p h i n g o l i p i d s h 3 v e b e e n i d e n t i f i e d u s i n g 2U 1 I,' I p n a s e - s e n s i t i v e c o r r e l a t e d ri n . n . r . s p e c t r o s c o p y . A review of t h e usz o f n.rn.r.

methods,

a l o n g with energy c a l c u l a t i o n s , f o r t h e

s t u d y or' s o l u t i o n c o n f o r m a t i o n s a n u d y i i a n i c s o f a s p a r a g i n e - l i n k e d oligosaccharidss

6

o f g l y c o p r o t e i n s has a p p e a r e d .

id.1n.r.

o f lquclei o t h e r t h a n

Kefererice t o t h e use of

29

1 II

5d

o r "i:

S i resonancas i n neteroriuclear cor-

r e l a t i o n s f o r t n e s t u d y o f o l i g o s a c c h a r i d e s h a s b e e n iuade a b o v e . 'fhe r e s u l t s d e m o n s t r a t a d t n e u s e f u l n e s s o f t h e r e s o n a n c e s f o r t h e a n a l y s i s of oligosaccharides, number o f i n i t i a l hyaroxy-

t h e number o f l i n e s e q u a l l i n g t h e

groups.

42-44

Helerences

rl.K.Mcfntyre and G.W.Smal1, Anal. Chern., 1987, 2 , 1dO5 (Chem. Hbstr., 1467, =I, 23 5 6 6 ) . C.l.larat, C.K.Tarave1, and I.I.R.Vignon, Carbohydr. &, 1967, 265. J.K.Saunders and J.D.Stevens, ivlagn. Reson. Chern., 1986, 2 , 1 ~ 2 3 (Chem. Abstr., 1987, x b , 00 1 2 2 ) . d.il.Pinto, h.~.Scnlegel, and S.Wolre, @. J . Chem., 1487, 65, l b 5 8 . J.-P.Praly and ~S.U.Lemieux, Can. J. Chem., 1987, g ,213. A.uuedraogo, i'l.'l'an Phan Viet, J.K.Saunders, and J.Lessard, Can. Chem., 1987, 1761. H.booth, n.A.ihecihair, and S.A.Keadsnaw, Tetrahedron, 1387, 43, 4644. M.ChniielewsKi, J .Jurczak, d.Priebe, and U.IIorton, riagn. Keson. Chern., 1467, 42, 161 (Chem. Abstr., 1967, 1 0 7 , 217 941).

m,

z,

J.

232 Y

lu 11 IL

13 14

15

I:, 17 10 19

LU

Carbohydrate Chemistry B.Coxoii, iVlagn. l i e s o n . Chern., 1986, &, lob3 (Chern. A b s t r . , 1987, 107, 134 557). d . f i . U ' A c c o r s o a n d I . h . L . r h i e 1 , d e v . L a t i n o a r n . Q u i m . , 19&, lJ, 36 (Cheni. A w t r . , 1Yo7, 18 909). n . B . 0 ' d c c o r s o a n d l . l h . b . T h i e 1 , C a r b o h y d r . &, 1507, 107, 19. i!.d.U'Accorso a n d I.id1.E.Thiel, C a r b o h y d r . &, 1967, 127, 301. l\l.C.iviatulewicz, L . A . 5 t o r t z , 1 i . l Y . J a r r e t , a n d A . S . C e r e z o , J. C a r b o h y d r . Lhern., 1 ~ 8 7 ,4 , 515. A . S . b e r i a n n i a n d U.Ivl.Chiprnan, &. 2henl. SOC., 1587, 5297. A . L . S a l i n a s , J . b . S p r d v i e r o , a n d V . U e u l o i e u , C a r b o h y d r . I(es.,lY87, 1 3 , 11. L .tl. K o o l e , H . I v i . h ~ i c , A . i V y i l a s , a n d J . C h a t t o p a d h y d y d , Cnein. , 14137, 9 3 , LUb9. 1 . H n g e l o t t i , m . K r i s ~ o , 1 .c)'Conner , drid A . > . b e r i a n n i , J. 4. &, 1 4 8 7 , 129, 4404, A . U .Karimari a n d ri. Y .Khan, d. P u r e A p p l . b c i . , lYbu, 2, ~7 A b s t r . , l~b7,2 7 , ~ 3 7155). f . i i . L a n o , C . F o c e s - k o c e s , J . J i m e n e z - b a r b e r o , A.Alemany, i.i.dernabe, a n d 1'1. m r t i n - L o r l i d s , J. chem. s o c . , f ' e r k l n rraris. 1987, 791. J . C . C i i r i s t o t i d e s d n d U . b . D a v i e s , J. Chern. a o c . P e r k i n r r a n s . 1,

a,

m,

J.

&. A.

w. (w.

r,

1987, Y7. Ll

2L L3

L4 L3

Lc,

d . L . b a s t r y , h . ' l ' a h e g o s h i , d n d L.A.DlcUowe.11, C a r b o n y d r . &, 1367, &, lul. t'.-L.Jansson, L . r \ e n n e , a n d L . b c h w e a a , J. Cheiti. S o c . P e r h i n r r a n s . 1, 1907, 377. ~ ~ . I . ~ . A b d e l - ~ ' i a l ic(k ., J . P e n g , a n d A . a . P e r l i r i , C a r b o h y d r . &, 1907, 159, 11. ii.L)rirui, Y . h i s h i d a , h . H i g u c i i i , r ~ . r A o r i , a n d ~ . P l e g u r o ,Can. J. Chem.,

1367, g ,1145.

K . l z u m i , a k r i c . dioi. Lnem., 19b7, i l , 17L~. ~ r b. o s n o v s K y , IY .i'I.Kao, J L u k s z o , a n d 2 . C . B r a s c h , g. I A a t u r f o r s c h . , nor#. Ur#. Chem., lYt(b, 4_1, 1 ~ 9 3(Cnem. A b s t r . , 1987, 107,

m,

.

.u

Y O 479). L7 r .H . L a n o , C . F o c e s - Y o c e s , J J i m e n e z - b a r b e r o , Pi. b e r r i a b e , arid n.lviartiii-Lonias , CxDohyTdr. b, 1YL7, E U , 1Uu. I.-C.hu, i?.b.cloe~jiari, a n d Y . K i s h i , C)r#. Chem., IYbl, j r , r d 1 Y . LO lY87, 1 3 , 14 t'.l(ovac, 1i.J .L. Yeh, arid C.P.J . b l a u a e m a n s , C d r b o h y d r . &,

.

J.

LA. XJ

Jl

w,

L.K.ileisori, C a r b o h y d r . lybf, %, ~ 7 3 . ~ . A . A . v a n docchel, s . F . v d n ftelst, b . n . d a b e n a a r s , J.K.ilellerna, h . p a u l s e n , l r a v . Cliiin. P a y s - B a s , 1467, ' i . p e t t t r s , pollex ex, a n d V . ~ l n n w e l l , IS, 19 (Ctiern. A b s t r . , 1Yd7, 170 J&)iu.h.be Vries a n d Ii.1+1.Luch, C a r b o h y d r . &, 1967, i62, 1. b . r ' e r m a n d j u n , d.f"erly, i~i.L*vel, a n d P . L e r r a n c i e r , C a r b o h y d r . lYdl, L L , 23. r .ii.Cano, ~.boces-Foces,J . J i l n e n e z - U a r w r o , ~ . k l e i n d . n y , I ' i . t k r r i a b e , a n d 1'1. Ildrtlii-Loi!ias, J. Chein., 13df, >L,3 A l . ~ . L . b i r n b a u m , K.koy, ~ . - - K . k 5 r i s s o n , a n d H . J . J e n n i n g s , L. C a r b o n y d r . Cheni., 1Yb7, 2, 17. K.Luthrnan, A . C l a e s s o n , L . K e n n e , a n u I . C s o r e g h , C a r b o h y a r . -, 1967, l ? U , lb7. Y I . L n r i s t i a n , b . b c h u l t z , H . i l . i 3 r a n u s t e t t e r , a n d ~ . L b i r d l , L a r b o h y a r . *, 1Y87, l-@, 1. b .li.Iiornans, I<. H . b w e ~ , J tjoyu, N . S o l r e , a n d l'.k.Kademacner , P r o c . Natl. Acad. S c i . L.S.A., lrb7, ~ L U L(Chem. A b s t r . , 1987, 106, L l U 319). B.Perly, V.~ossennec, P.Berthault, and ~ i . P e t i t o u , Tetrahedron Lett., 1587, 3331. W.J.L,OUX a n d L . J . L l n k e f e r , C a r b o n y u r . d e s . , 1987, 1 5 9 , 191. I).A.Lurmning a n d J . P . C a r v e r , b i o c h e m i s t r y , 1987, 20, bbb4 (Chem. A b s t r . 1Yo7, 1 0 7 , 1 7 1 f 4 1 ) . J . S c h r a r n l , b . P e t r a k o v a , J .Mirsch, J . L e r n a k , V . C h v a l o v s ~ y , k.?eeaar, a n d b . Lippriiaa, C o l l e c t Czecti. Cneiu. Commun. , 19b7 , 52, L4GO.

Lu,

SL 33 34

33 A

37 3b

39 4U

41 4L

a.

a,

m.

.

2,

e,

233

21: N . M . R . Spectroscopy and Conformational Features 43

J . S c h r a m 1 , E . P e t r a k o v a , a n d J.liirsch, Nagn. Reson. Chem., 1 9 6 7 , 25, 7 5 176 349). (Chem. A b s t r . , 1 9 6 7 , &7, 44 d . P e t r a K o v a , J.Schrain1, J . i i i r s c n , M . d v i c a l o v a , J . Z e l e n y , a n d V.Chvalovsky, C o l l e ct . Czech. -Chem. Conmun., 1 9 8 7 , 52, 1501. 45 b .> .namyan, G .ri. L l p K i n d , A . s. ShashKov, II .b. N i r a n t ' e v , a n d I(. h Kochetkov I d i o o r g . K h i m . , 1 9 8 6 , 12, l l U l (Chem. A b s t r . , 19d7, 107, 76 1 0 8 ) . 4 0 ib1.L.Jimeno, k.~'erriandez-i.layoralis, I~l.Plartin-Lomas, a n d A.Alernany, lYd7, &I, 144. Cdrbohydr. &, 4 i f . b . b o e K j i a n , 'l'.-C.du, H.-i.Kanb, a n d Y.kishi, Or#. Chenl., 1987, 5 2 , 4623 * 46 a . ~ . u a b i r a d , Y.hiang, P . b . b o e ~ ~ i a n a, n d l . k i s l i i , J . Cherri., 1 9 6 7 ,

.

J.

a.

z,4dL7.

4Y 3U

31 33L

33 34

l \ . h a r c n e t t i n i , ~ . P o g l i a n i ,C.Kossi, a n d S . U l b i a t i , spectres. L e t t . , 1Y07, @, d l ( C h e m . A b s t r . , 1 9 6 7 , 1 0 7 , 113 t 7 b ) . 1 9 8 7 , &, 1. Pi.lKura dlld K . H i K i c l i i , Carboliydr. L . b z i l a g y i , Cdrbohydr. Kes., 1967, 170, 1. L.Lerrier a n d ~ . d a x ,C a r b o h y d r . &, 19b7, 33. r l . f a u l s e n , l . P e t e r s , V . s i n n w e i 1 , a n u b..I'ieyer, Larboilyur. I(es., 1487, 165, 231. I . Yainamoto, i h o u e , r( . C n u j o , a n d b . n o b a y a s h l , Carbohycrr 1987,

w,

g,

4b6,

50 37

136.

.

. m,

l . F u r o , I . i - " O c s i K , K.'l'anpa, & . l e e a a r , a n d L-Lippinaa, u r b u h y d r . Kes., 1967, l&, ~ 7 . L . - l . Yan, 8 . 1 i . i ~.Kao, a n d C.A.6usl1, J . K . hem. S O C . , 1987, 1 2 , 7 6 ~ . J . b a b r o w s ~ d , 8 . c J C h d r t I ri.Kordowicz, aild t).kianiland, Magn. I<eson. Lrieni., 14d/, 4 , 3% (Chem. A b s t r . , i 9 d 7 , LC7, L17 3 t U ) . b . d . l i o m r i s , K . A U w e l c , dnd l'.IJ.kadelnacner, B i o c h e m i s t r y , lY87, &, 6571 C k m . A b s L r . , 1907, l-01, 171 011).

22 Other Physical Methods

1

1.r. Spectroscopy

A review on the vibrational spectra of cacbohydrates has appeared. 1 The i . r . and Raman spectra of D-glUCOSe and five selectively deuterated derivatives in the solid state have been further detailed (c.f. V01.20, p.236) . d 1.r. spectra of trehalose, its g-deuterated analogue, and maltose have been recorded at 18 and 300 K, the characteristic region of torsional vibration frequencies of hydroxy groups determined, and the hydrogen bonding analysed. Time dependent F.t.i.r. spectra of a-D-galactose, a-D-glucose-1-d, -2-d, -5,6,6-d and a-D-fucose in aqueous solution were recorded and -3 interpreted in terms of gradual mutarotation. I' F.t .i.r. spectroscopy was used to determine that the conformation of guanosine 5'-monophosphate changes from C2'-endo, anti to C3'-endo, anti on interaction with magnesium (11) ions . 5

2

Mass Spectrometry

The principles and use of direct/desorption c.i.-m.s. for the structural analysis of carbohydrates and oligosaccharides have been reviewed (54 refs. ) . 6 Fast-atom bombardment (FAB) m.s. has been used in the analysis of oligosaccharides, e.g., malto-oligosaccharides up to DP 17, as their N-glycosyl-2-aminopyridine derivatives, of oligosaccharides containing N-substituted mono- and di-amino-sugar units in connection with the characterization of Pseudomonas aeruginosa lipopolysaccharide fragments , of oligosaccharide antibiotics such as the octasaccharide antibiotic everninomycin in which the sequence of sugar residues was determined,9 and of acetylated and acetolysed high-mannose core oligosaccharides from glycoproteins, produced from just a few micrograms of isolated oligosaccharide . l o The fragmentations of oxyanions [M-HI- generated from alkyl glycosides under FAB-m.s. conditions have been studied using mass-analysed ion kinetic energy spectrometry; the main pathway for methyl glycosides 11 involved loss of methanol.

235

22: Other Physical Methods

The positive and negative ion laser-desorption F . t . r n . s . of ascorbic and isoascorbic acids and their Na+ and K+ salts were recorded, and a number of differences between these results and those obtained with a related technique (Vo1.18, p.155) were 12 discussed. E.i.-m.s. can be recorded on oligosaccharides composed of 0-methyldeoxyhexoses and dideoxyhexoses, because they are not as involatile as normal oligosaccharides. The high-resolution e.i.m.s. fragmentation patterns of methyl B-pahybioside (1) and the oleandrotetrose orthenthose were interpreted .I3 The differing mass spectra of several diastereomeric pyrimidine nucleosides have been described. 14

W0QMe

HO

(I)

OMe OH

The capillary g.c.-e.i.- and c.i.(NH ) - m . s . o f partially 3 methylated and acetylated derivatives of 3-deoxy-2-keto-aldonic acids and 3-deoxyalditols has been reported in preparation f o r the methylation analysis of KDO units in bacterial lipopolysaccharides.15 In the c.i.(i-C4H10)-m.s. ol' some branched-chain hexopyranoside derivatives (with one or two Ac, C 0 2 M e , CONH2 or CN groups at C - 3 ) , the [M+C H 1' and several primary fragment ion intensities were 4 9 found to be dependent upon the nature and stereochemistry of the 16 C - 3 substituent. A number of reports have appeared on the'coupling of h.p.1.c. and m.s. systems for the analysis of sugars. Thermospray h.p.1.c.m.s. has been applied to the analysis of mono- and di-galactosyl diglycerides which are major components of plant cell membranes, 1 7 desulpho-glucosinolates as models for natural glucosinolates, and 18 the cytokinins zeatin, its riboside, and their dihydro-analogues, I 1 znd 2 , 3 -dideoxyinosine as a degradation product of 2',3'-dideoxyadenosine in biological fluids . l9 A dual beam thermospray interface, which permits introduction of the ammonium acetate solution, necessary f o r this mode of ionization, independently from the h.p.1.c. eluant, has been demonstrated for sucrose and adenosine among other compounds .20 The eluant f r o m capillary h.p.1.c. columns of 0.22 or 0.26 mm i.d. silica tubing can be directly introduced into m.s. systems. Systems with such direct liquid introduction have been successfully used for the analysis of

236

Carbohydrate Chemistry

22 anomeric pyridine C-nucleosides, raffinose and cardenolides , and some oligosaccharides where FAB ionization was induced through inclusion of glycerol in the eluant.23 A moving polyimide belt h.p.1.c.-m.s. interface using FAB desorption in the absence of added matrix, has been demonstrated for model oligosaccharides and high mannose oligosaccharides from animal urine.24

3 X-ray Crystallography In an attempt to understand the effect of raffinose on sucrose morphology, a detailed crystallographic study on the theoretical surfaces of sucrose was undertaken, and face by face kinetics were determined for single and twin sucrose crystals as affected by raffinose,25 The occurrence of propeller twisting in single crystals of nucleosides was demonstrated by analysis of material from the Cambridge database. 26 Specific crystal structures have been reported as follows: Free Sugars and Simple Derivatives Thereof.- B-D-Xylopyranose (a refinement, correcting an angle) ,27 2,3: 4,5-di-g-isopropylidene-BD-fructopyranose ,28 3,4,6-tri-~-acetyl-1,2-~-isopropylidene-a-Dgalactopyranose ,29 3 ,4-di-O-acetyl-l,2-Q-(g) and (S)-( l-cyanoethylidene)-a-D-xylopyranose ,30-and 1,2 ,3 ,4-tetra-g-acetyl-B-D-glucopyranos-6-yl 1,2:5,6-di-~-isopropylidene-~-D-glucopyranos-3-y1 methyl phosphate.31 Glycosides and Derivatives Thereof.- n-Octyl a-D-glucopyranoside mono- and hemi-hydrate ,32 a triterpenoid glycoside containing 2-deoxy-D-glucose ,33 a diterpene B-D-xylopyranoside ,34 methyl 2 - d e o x y - 3 , 5 - d i - ~ - ( ~ - n i t r o b e n z o y l ) - B - D - e r y t h r o - p e n t o f u r a n o s i d e y 35 methyl 2,4,6-tri-Q-pivaloyl-a-D-glucopyranoside and methyl 4,6-Q-benzylidene-2-0- and 2,3-di-~-pivaloyl-a-D-glucopyranoside,36 and the C-glycosides diazomethyl B-D-galactopyranosyl ketone ,37 and 3-(2-deoxy-a-D-erythro-pentofuranosyl)pyridine. 38 Tri- and Tetra-saccharides.- A triterpene trisaccharide [with an a-L-Rhap-( 1+4)-B-D-Glcp-( 1+6 )-B-D-Glcp+residuel y 3 9 and stachyose 40 [a-D-Galp-(1+6)-a-D-Gal~-(l-+6)-a-D-Glcp-(l~2~-a-D-Fru~~. 2 Anhydro-sugars.- Methyl 6,6-C H 2 1-2,6-di-Q-acety1-3,4-anhydro-aDL-galactopyranoside, 41 3-0-( 2 ,3-anhydro-4-deoxy-a-L-lyxo-hexopyranosyl) -1 ,2 : 5 ,6-di-~-isopropylidene-a-D-glucopyranose,42 and methyl 3,6-anhydro-B-L-gulofuranoside. 43 Halogen-, Nitrogen-, and Sulphur-containing compounds.- The 2,3,4,6-tetra-0-acetyl derivatives of 1-C-chloro-a-D-glucopyranosyl

237

22: Other Physical Methods

bromide"

and 1-C-bromo-a-D-galactopyranosyl cyanide 45 the

pyranosyl fluoride (2) of KDO,46 3,5-g-(R-)-benzylidene-6-deoxy-6the 7-b romo- o ct o side iodo- 1 2-2- i sopropy 1ide ne- a-D - g 1u c o f UP anose

( 3 ) ,48 the 4-iodo-neuraminic acid analogue (4),49 2-deoxy-2-C (4,4dimethyl-2,6-dioxocyclohexylidenemethyl)amino~-~,~-D-glucopyranose,50 the 1-amino-1-deoxy-D-fructose derivative ( 5 ) ,51 2-azido3,~-~-benzylidene-2-deoxy-D-ribono-1,5-lactoney 2-azido-2-deoxy-Dribono-1 ,4-lactone , and 1,4-dideoxy-l ,4-imino-L-ribitol 52 1 5dideoxy-~-0-(a-D-glucopyranosyl)-ly5-imino-~-methyl-D-glucitol, 53 2-deoxy-E- ( 4-carboxyphenyl)-B-D-ribopyranosylamine ,54 4-(N-acetyl2 ,3 4-tri-~-acetyl-B-L-arabinopyranosylamino)azobenzene ," the B-D-gluco-lY2-cyclic urethane (6), its D-xylo-analogue, and the a-L-arabino-l,3-cyclic urethane (7),56 the imidazole-2-thione the f o u r derivative (8), 5 7 the oxime of 1,5-anhydro-D-fr~ctose,~~ tetraacetylated glycopyranosyl cyanides with the B-D-gluco-, B-Dmanno- , a-D-ribo- , and a-D-ido- configurations 59 the 13-D-galact o2-heptulopyranosonitrile ( 9 ) ,45 2 ,4:3 ,5 - d i - 0-- b e n z y l i d e n e - D - a r a b i n o s e diethyl dithioacetalY6' and the glycosyl dithiophosphate (10).61

(2 )

0Bz

(5)

(6)

OAG

(91

(7)

(13 ) (12)

(14)

CHZOH

Branched-Chain Sugars .- The cyano-sugars (11)62 and (12) y63 dipolar cycloadduct (13). 64

and the

Alduloses, Sugar Acids, and their Derivatives.- The tri-g-isopropylidene derivative ( 14) of D-glucosone hydrate ,65 ammonium 3-deoxy-

238

Carbohydrate Chemistry

D-manno-2-octulosonate (KDO),66 and its 2-deoxy-analogueY i .e., 2 ,6-anhydro-3-deoxy-D-glycero-D-talo-octonate ,67 and the 2-noneno1,4-lactone (15). 68 Inorganic Derivatives.- 5,6-Dideoxy-l,2-~-isopropylidene-3-~methyl-6-~-nitro-5-~-~dimethoxyphosphinyl~-B-L-idofuranose (note: the diagram in the paper appears to be the C-5 epimer with the D-pluco configuration) ,69 and the nickel (11) dichloride complex 70 with ~,~-diC~-(B-D-mannopyranosyl)-2-aminoethyl~ethylenediamine. Alditols, Cyclitols and Derivatives Thereof.- lY2:3,4:5,6-Trianhydro-D-iditol ,71 the a-pyrone plant natural product synrotolide

(16)y72 the D-Ealacto-pentitol-1-ylated heterocycles ( 1 7 ) 73 and ~ ~ (R)-camphanate ester (19) of myo(18) y74 L - ~ h i r o - i n o s i t o l ,the i n o s i t o l Y 7 a n d the 1:l-complex of caffeine with potassium chlorogenate (the salt of an 2-caffeoyl-quinic acid) .77

Nucleosides and their Analogues and Derivatives.- 1-Methyladenosine ,7B 3-me thylcytidinium nitrate ,7 9 2 ' ,3 ' ,5 ' -tri-g-acety 1-8-bromo5 '-azido-5'-deoxyadenosine y80 2' ,5'-anhydro-arabino~ylcytosine,~~ 1-B-D-arabinofuranosylcytosine, 82 2 I-c-methyl-uridine ,83 ethyl-1-BD-arabinofuranosyl-2-cyanomethyl-l~-pyrrole-3-carbox~late,84 3-benzoyloxy-l-B-D-ribofuranosyl-pyrazole-4-carboxylic acid, 85 l-(2,3,5-tri-~-benzoyl-B-D-ribofuranosyl) derivatives of tetrahydro2H-lY3-diazepine-2,4(3g)-dione and 6,7-dihydro-25-1,3-diazepine2( 3H)-one ,86 cis-(5~,6~)-5,6-dihydroxy-5,6-dihydrothymidine(a 88 radiation product of thymidine) ,87 3'-azido-~'-deoxy-thymidine , 2 '-deoxy-hJ6-( 4-nitrobenzyl)-adenosine ,89 3' ,5 '-di-g-acetyl-2 '-deoxysdenosine 3'-g-acetyl-2 '-deoxy-adenosine ,91 2 ' - d e o ~ y t u b e r c i d i n , ~ ~ 3 '-deoxytubercidin and 3-deaza-3'-deoxy-adenosine , 9 3 g-benzoyl-5 ' the C-nucleos ides 0-tert-butyldimethyls ilyl-2 ' -deoxy-adenosine y 9 1 ,3-dimethyl-8-B-D-ribofuranosyl-xanthine r n ~ n o h y d r a t eand ~ ~ 5-c( 2-amino-2-deoxy-B-D-glucopyranosyl) barbituric acid , 9 6 and the carbocyclic 2' -deoxyuridine analogue (20).97 Others.- The trimer (21) f r o m L-ascorbic acid and methyl vinyl ketone. 98

239

22: Other Physical Methods

4

E.s.r. Spectroscopy

Two articles have reviewed conformations, deduced from e.s.r. hyperfine coupling constants, of radicals generated by abstraction of Br, I or SePh from C-1, -2, -3, or -4 of alkylated and acylated

pyranoses with photolytically generated stannyl radicals. The preferred conformations of n-type C-1 1-deoxypyranosyl radicals were discussed in terms of stabilization by adjacent B-C-0 bonds,99 a novel 1+2-acetoxy-group migration in a tetraacetyl-galactosyl radical was reported, and the mechanism of interaction of nitrosugars with stannyl radicals was discussed. l o o F o u r phosphoruscentred radicals were identified in an e.s.r. study of a single crystal of the phenoxyphosphoryl xylofuranose derivative (22) X-irradiated at low temperature (‘~77K).

An e.s.r. analysis of

the degradation products from y-irradiation of a-D-glucose at 77 to 415 K confirmed the decomposition of the initial radicals at 150-170 K to give sugar acids, and the formation of secondary radicals through dehydration of the initial radicals.102

5 Polarimetry, Circular Dichroism and Related Studies A semiempirical theory of optical activity, which incorporates high energy excited states so as to be relevant in the vacuum U . V . and which can be applied to complex molecules, has been applied to cyclohexane-polyols. A moderately good correlation with experimenta1 data was attained. O.r.d., c.d., and U.V. spectroscopy have been used to investigate the optical contributions of the nitrate

240

Carbohydrate Chemistry

group in eight derivatives of gluco- and manno-pyranoses having one or two nitrate groups at C-1, -2, or - 3 , 1 ° 4 and of the aglycones in eighteen aryl 6-D-glucopyranosides."5 Pairwise interactions of acetyl groups accounted f o r the observed relationship between the c.d. spectra and stereochemistry in eight peracetylated 1,5-anhydropentoses, -hexoses and certain deoxy-analogues. lo6 A c.d. study of four diselenides, e . g . , (23) and (241, and one ditelluride The Cotton effects permitted the assignment of Cotton effects.

iRoQeT r

CH~OR

i

-Se-CH2

I

(23) R = A c or -?\P ,O , o x

o f bidentate complexes between M O ~ ( O A C )and ~ some sugar diols have been studied, and it was proposed that the absolute configuration of acyclic vicinal threo and primary-secondary diols can be 108 determined in this way. The exciton chirality method has been discussed. It is a p o w e r f u l tool for determining the stereochemistry of organic molecules containing hydroxy-groups at stereocentres, and has been applied to oligosaccharides on a microscale using exciton chromophores in derivatives, e . g . , benzoate esters, benzyl ethers. 109

References 1

2 3 4 5 6 7 8

9 10 11 12

M.Mathlouthi and J .L.Koenig, Adv. Carbohydr. Chem. Biochem. , 1986, 44, 7 (Chem. Abstr. , 1987, 106, 172 156). G.Longhi, G.Zerbi, G.Paterlini, L.Ricard, and S.Abbate, Carbohydr. Res., 1987, 161,1. E .V.Korolik , N .V.Ivanova, R.G .Zhbankov, and T .E .Kolosova , Zh. Prikl . Spektrosk., 1986, 45, 865 (Chem. Abstr. , 1987, 107, 134 577). D .M.Back and P .L.Polavarapu, Carbohydr. Res. , 1987, 165, 173. T-Theophanidesand M.Polissiou, Magnesium, 1986, 2, 221 (Chern. Abstr., 1987, 106,27 491). V.N.Reinhold, Methods Enzymol., 1987, 138 (Complex Carbohydr., Pt E l , 59 (Chem. Abstr., 1987, 107,92 841). G.R.Her, S.Santikarn, V.N.Reinhold, and J.C.Williams, J. Carbohydr. Chem., 1987, 6, 129. Y.N.Elkin, Y.A.Knire1, E.V.Vinogradov, N.A.Paramonov, M.L.Troshkov, and I.H.Aminev, Bioorg. Khim., 1986, 12, 1658 (Chem. Abstr., 1987, 106,115 957). B.N.Pramanik and A.K.Ganguly, Indian J. Chem., Sect. B, 1986, 1105 (Chem. Abstr., 1987, 107,96 997). P.K.Tsai, A.Del1, and C.E.Ballou, Proc. Natl. Acad. Sci. U.S.A., 1986, 83, 4119 (Chem. Abstr., 1987, 107, 171 784). J.C.Prome, H.Aurelle, D.P+ome, and A.Savagnac, Org. Mass Spectrom., 1987, 22, 6 (Chem. Abstr., 1987, 107, 134 570). P.Coad, R.A.Coad, C.L.C.Yang, and C.L.Wilkins, Org. Mass Spectrom., 1987,

z,

24 1

22: Other Physical Methods

22, 75 (Chem. Abstr. , 1987, 107, 78 187).

1.3

14 15 16

17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

M.P.Khare and A.Khare, J. Carbohydr. Chem., 1987, 6, 523. L.Alder, G.R.Kim, R.Grimm, C.D.Pein, and D.Cech, Z. Chem., 1986, 5 , 136 (Chem. Abstr. , 1987, 106, 18 975). A.Tacken, H.Brade, P.Kosma, and D.Charon, Carbohydr. Res., 1987, 167,1. V.I.Kadentsev, I.A.Trushkina, O.S.Chizhov, V.V.Nemal’tsev, and V.A.Afanas‘ev, Bioorg. Khim., 1986, 2, 1561 (Chem. Abstr., 1987, 107, 176 334). H.Y.Kim, J.A.Yergey, and N.Salem, Jr, J. Chromatogr., 1987, 394, 155. F.A.Mellon, J.R.Chapman, and J.A.E.Pratt, J. Chromatogr., 1987, 394, 209. P.A.Blau, J.W.Hines, and R.D.Voyksner, J. Chromato r., 1987, 420, 1. L .Butfering, G .Schmelzeisen-Redeker, a n d J. Chromatogr. , 1987, 394, 109. E.L.Esmans, M-Belmans, I.Vrijens, Y.Luyten, F.C.Alderweireldt, L.L.Wotring, and L.B.Townsend, Nucleosides Nucleotides, 1987, 6, 865. H.Alborn and G.Stenhagen, J. Chromatogr., 1987, 394, 35. Y .Ito , T .Takeuchi, D .Ishii , M.Goto, and T .Mizuno, J . Chromatogr. , 1987, 391, 296. S-Santikarn, G.R.Her, and V.N.Reinhold, J. Chromatogr., 1987, 6, 141. G.Vaccari, G.Mantovani, G.Sgualdino, D-Aquilano, and M.Rubbo, Sugar Technol. Rev. , 1986, 2, 133 (Chem. Abstr. , 1987, 106, 166 417). C.C.Wilson and P.Tollin, Nucleosides Nucleotides, 1987, 6, 643. N.Zaman and S.F.Darlow, J. Bangladesh Acad. Sci., 1986, 10,177 (Chem. Abstr., 1987, 106, 41 goo). T.Lis and A.Weichse1, Acta Crystallogr., 1987, E,1954. F.H.Cano, C.Foces-Foces, J.Jimenez-Barbero, M.Bernabe, and M-Martin-Lomas, Carbohydr. Res. , 1987, 170,100. F.H.Cano, C.Foces-Foces, J.Jimenez-Barbero, A.Alemany, M.Bernabe, and M.Martin-Lomas, J. Chem, SOC. Perkin Trans. 11, 1987, 791. Q-Huang, S.Cai, and C.Tu, Jiegou Huaxue, 1986, 5, 116 (Chem. Abstr., 1987, 106, 166 670). G.A.Jeffrey, Y.Yeon, and J-Abola, Carbohydr. Res., 1987, 169, 1. N.Narendra, M.A.Viswamitra, R.Venkateswara, K.Sankaro Rao, and C.S.Vaidyanathan, Acta Crystalloqr., 1987, 1562. I.Tavanaiepour, W.H.Watson, F.Gao, and T.J.Mabry, Acta Crystalloqr., 1987, c43, 754. J.Raap, J.H.Van Boom, H.J.Bruins Slot, P.T.Beurskens, J.A.C.Van Wietmarschen, J.M.M.Smits, and C.A.G.Haasnoot, Acta Cryst., Sect. B: Struct. Sci., 1987, 43, 219 (Chem. Abstr. , 1987, 106,166 711) Z.Ruzic-Toros, B.Kojic-Prodic, L.Golic, and S.Tomic, Carbohydr. Res., 1987, 162, 171. J.R.Paddison, Jr., T.P.Haromy, M.Sundaralingam, R.W.Myers, and J.N.BeMiller, Carbohydr. Res., 1987, 168,7. K.G.Ford, S.Neidle, M.A.W.Eaton, T.A.Millican, and J.Mann, Acts Crystallogr., 1987, 1988. S.B.Mahato, N.P.Sahu, P.Luger, and E.MUller, J. Chem. SOC. Perkin Trans. 11, 1987, 1509. R.Gilardi and J.L.Flippen-Anderson, Acta Crystallogr., 1987, 806. J.W.Krajewski, P.Gluzinski, A.Banaszek, G.Argay, and A.Kalman, Carbohydr. Res., 1987, 166, 13. J.W.Krajewski, P.Gluzinski, A.Banaszek, G.Argay, and A. Kalman, Carbohydr. Res. , 1987, 166, 19. J.Kopf, P.KOl1, and G.M.Sheldrick, Carbohydr. Res., 1987, 168,115. J.P.Praly and G.Descotes, Tetrahedron Lett., 1987, 28, 1405. L-Parkanyi, A-Kalman, L.Somsak, and I.Farkas, Carbohydr. R 5 , 1987, 168, 1. M.Imoto, N.Kusunose, Y.Matsuura, S.Kusumoto, and T.Shiba, Tetrahedron Lett., 1987, 28, 6277. P.P.Giannousis, G.E.Hofmeister, K.L.McLaren, and M.C.Nolan, Acts Crystallogr., 1987, 2104. S.Danishefsky, M.P.DeNinno, and G.Schulte, J. Org. Chem. , 1987, 52, 3171. P.Luger, C.Zaki, H-N-Hagedorn,and R.Brossmer, Carbohydr. Res., 1987, 164,

.

36 37 38 39 40 41 42 43 44 45 46 47 48 49

242 50 51

52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69

70 71 72 73 74 75 76 77 78 79 80 81

82 a3 a4

Carbohydrate Chemistry 49. M.G.Garcia-Martin, C.Gasch, A.Gomez-Sanchez, M.J.Dianez, and A.L.Castro, Carbohydr. Res. , 1987, 162, 181. M.J.DiSnez, A.L6pez-CastroI and R.M&quez, Acta Crystallogr., 1987, E, 558. P.D.Baird, J.C.Dho, G.W.J.Fleet, J.M.Peach, and K.Prout, J. Chem. SOC., Perkin Trans. I, 1987, 1785. Y.Ezure, Y.Yoshikuni, N.Ojima, M-Sugiyama, K.Hirotsu, and T.Higuchi, Acta Crystallogr., 1987, 1809. S.Okada, H-Nakahara, H.Isaka, T.Taqa, and K.Miyajima, Chem. Pharm. Bull., 1987, 35, 2495. Z.Ciunik, Z-Smiatacz, and J.Sokolowski, Carbohydr. R e s , 1987, 163, 149. F.H.Cano, C.Foces-Foces, J.Jimenez-Barbero, A.Alemany, M.Bernabe, and M.Martin-Lomas, J. Org. Chem., 1987, 52, 3367. M.D.Estrada, A.Conde, and R.M&quez, Acta Crystallogr., 1987, 1134. G.Deffieux, R.Baute, M.-A.Baute, M.Aftani, and A.Carpy, Phytochemistry, 1987, 26, 1391 and 1395. 161. J.Kopf and P.KGl1, Carbohydr. Res., 1987, 2, T.B.Grindley, S.Kusuma, T.S.Cameron, and A.Kumari, Carbohydr. Res., 1987, 159, 171. Z.Ciunik and J.Jasinka, Carbohydr. Res., 1987, 159, 5 3 . K.Luthman, M.Orbe, T.Waglund, and A.Claesson, J. Org. Chem., 1987, 52, 3777. B.Giese, J.Dupuis, M.Leising, M.Nix, and H.J.Lindner, Carbohydr. Res., 1987, 171,329. H.Gnichte1, L-Autenrieth-Ansorge,J.Dachmann, P.Luger, and A.Duda, J. Carbohydr. Chem., 1987, 6, 673. C.W.Holzapfe1, G.J.Kruger, M.S.van Dyk, and L.den Drijver, Lcic Crystalloqr., 1987, E,372. G.I.Birnbaum, R.Roy, J.-R.Brisson, and H.J.Jennings, J. Carbohydr. Chem., 1987, 6, 17. K.Luthman, A.Claesson, L.Kenne, and I.Cs&-egh,Carbohydr. Res., 1987, 170, 167. K.Furuhata, S.Sato, K.Anazawa, M.Goto, H-Takayanagi, and H.Ogura, Chem. Pharm. Bull., 1987, 35, 3609. M.Yamashita, M.Sugiura, Y .Tamadat T-Oshikawa,and J.Clardy, Chem. Lett. , 1987, 1407. S.Yano, T-Takahashi, Y.Sato, K.Ishida, T.Tanase, M.Hidai, K.Kobayashi, and T.Sakurai, Chem. Lett., 1987, 2153. P.Kzl1, J.Kopf , J.O.Metzger, W.Schwartinq, and M.Oelting, Liebigs Ann. Chem., 1987, 199. M.T.D.Coleman, R.B.English, and D.E.A.Rivett, Phytochemistry, 1987, 5, 1497. M.J.Di&ez, J.GalSn, A.G6mez-S&chezI A.L6pez-CastroI and M.Rico, J. Chem. SOC. Perkin I, 1987, 581. M.J.DiSnez, R.Vega, A.L;pez-Castro, and R.M&quez, Acta Crystallogr., 1987, c43, 1158. G.A.Jeffrey and Y.Yeon, Carbohydr. Res., 1987, 159, 211. D.C.Billington, R.Baker, J.J.Kulagowski, and I.M.Mawer, J. Chem. SOC., Chem. Commun., 1987, 314. R.Martin, T.H.Lilley, C.P.Falshaw, E.Haslam, M.J.Begley, and D.Magnolato, Phytochemistry, 1987, 26, 273. Y.Yamagata and K.-i.Tomita, Acta Crystallogr., 1987, G & , 2117. M. Jask6lski and M.Wiewi6rowski , Acta Crystallogr. , 1987, 89. R.Boyd, J.N.Low, and P.Tollin, Acta Cr stallogr., 1987, E l 1370. G.I.Birnbaum, M.Budesinsk<, a n d e J . Chem., 1987, 65, 271. 1731. G.Biswas, A-Banerjee, and W.Saenger, Acta Crystallogr., 1987, L.N.Beigelman, B.S.Ermolinsky, G.V.Gurskaya, E.M.Tsapkina, M.Ya.Karpeisky, and S.N.Mikhailov, Carbohydr. Res., 1987, 166,219. S.B.Larson, N.S.Girgis, H.B.Cottam, and R.K.Robins, A c t a Crystallogr., 1987, ~ 4 3 ,1226.

c,

c,

22: Other Physical Methods 85 86

87 88

89 90 91 92 93 94 95 96 97 98 99

100 101 102 103 104 105 106 107 108 109

243

Y.S.Sanqhvi, K.G.Upadhya, N.K.Dalley, R.K.Robins, and G.R.Revankar, Nucleosides Nucleotides, 1987, 6, 737. P.A.Sulton, V.Cody, and V.A.Marquez, Nucleosides Nucleotides, 1987, 6, 613. F.E.Hruska, R.Sebastian, A.Grand, L.Voituriez, and J.Cadet, Can. J. Chem., 1987, 65, 2618. G.I.Birnbaum, J.Giziewicz, E.J.Gabe, T.-S-Lin, and W.H.Prusoff, Can. J. Chem. , 1987, 65, 2135. J.W.Quai.1, L.T.J.Delbaere, and A.R.P.Paterson, Nucleosides Nucleotides, 1987, 5, 877. L.H.Koole, H.M.Buck, J.A.Kanters, and A.Schouten, Can. J. Chem., 1987, 65, 326. J.N.Low, P.Tollin, and R.A.Howie, Acta Crystallogr., 1987, E l 2184. V.Zabe1, W.Saenger, and F.Seela, Acta Crystallogr., 1987, E l 131. R.McKenna, R.Kuroda, S.Neidle, and P.Serafinowski, Acta Crystallogr., 1987, C43, 1790. S.K.Burley and A.H.-J.Wanq, Acta Crystallogr., 1987, *, 988. H.Maluszynska and G.A.Jeffrey, Carbohydr. Res., 1987, 169, 35. M.Millan, C.F.Conde, A.Conde, and R.M&quez, Acta Crystallogr., 1987, E l 1138. K.Biggadike, A.D.Borthwick, A.M.Exal1, B.E.Kirk, S.M.Roberts, P.Youds, A.M.Z.Slawin, and D.J.Williams, J. Chem. SOC., Chem. Commun., 1987, 255. R.Arnold, G-Fodor, C.George, and I.Karle, Can. J. Chem., 1987, 65, 131. H.G.Korth, R.Sustmann, J.Dupuis, K.S.Groeninger, T.Witze1, and B.Giese, NATO AS1 Ser., Ser. C, 1986, 189 (Substituent Eff. Radical Chem.), 297 (Chem. Abstr. , 1987, 107, 176 327). R.Sustmann and H.G.Korth, J. Chem. SOC., Faraday Trans. 1, 1987, 83, 95. A.Celalyan-Berthier, T.Berclaz, and M.Geoffroy, J. Chem. Soc., Faraday Trans. 1, 1987, 83, 401. G.V.Abagyan and S.M.Atashyan, Arm. Khim. Zh., 1987, 40, 3 (Chem. Abstr., 1987, 107,217 942). B.K.Sathyanarayana and E.S.Stevens, J. Orq. Chem., 1987, 52, 3170. K.Satsuma Bayashi and Y.Nomoto, Nippon Shika Daiqaku Kiyo,Ippan Kyoiku-kei, 1985, 2, 77 (Chem. Abstr. , 1987, 107,237 134). K.Satsuma Bayashi and Y.Nishida, Nippon Shika Daigaku Kiyo, Ippan Kyoiku-kei, 1986, 15,79 (Chem. Abstr., 1987, 107,237 147). P.Salvadori, C.Bertucci, D.Pini, and G.Zullino, Carbohydr. Res., 1987, 167. 9. Gichalska and G.Snatzke, Liebigs Ann. Chem. , 1987, 179. A-Liptak, J.Frelek, G.Snatzke, and I.Vlahov, Carbohydr. Res., 1987, 164, 149. K.Nakanishi, M.H.Park, R.Takeda, J.T.Vazquez, and W.T.Wiesler, Stereochem. Orq. Bioorg. Transform., Proc. Workshop Conf. Hoechst, 17th, 1986, (Pub. 1987), 303 (Chem. Abstr. , 1987, 107,115 878).

23 Separatory and Analytical Methods

1

Chromatographic Methods

General.A r e v i e w h a s a p p e a r e d on t h e p u r i t y a s s e s s m e n t o f b i o l o g i c a l l y a c t i v e c a r b o h y d r a t e s , e s p e c i a l l y by h . p . 1 . c . 1

Gas-Liquid

Chromatography.-

Unless otherwise s t a t e d , a l l analyses

were performed on c a p i l l a r y g . c .

columns.

The p r e p a r a t i o n a n d c h a r a c t e r i z a t i o n by g . c . - m . s . methylated and a c e t y l a t e d 3-deoxy-octitols 3-deoxy-heptitols,

of partially

( c . f . V01.20, p . 2 4 7 ) ,

and t h e c o r r e s p o n d i n g 3-deoxy-2-ketoaldonic

a c i d s has been r e p o r t e d i n connection with t h e methylation a n a l y s i s of 3-deoxy-2-ketoaldonic acid u n i t s i n b a c t e r i a l lipopolysacchar i d e s .2 Permethylated d e r i v a t i v e s of 3-deoxy-2-ketoaldonic acid 5 - p h o s p h a t e s Y s u i t a b l e for g . c . - m . s . ,

have a l s o been prepared.

Glucosamine and g a l a c t o s a m i n e r e l e a s e d from g l y c o s a m i n o g l y c a n s i n b l o o d a n d p l a s m a by h y d r o l y s i s h a v e b e e n q u a n t i t a t i v e l y d e t e r m i n e d by a n a l y s i s o f t h e d e r i v e d a c e t y l a t e d a m i n o a l d i t o l s on a p a c k e d column.

4

Aldoses and alduronic a c i d s have been simultaneously analysed

as t h e i r p e r a c e t y l a t e d a l d i t o l a n d N - p r o p y l a l d o n a m i d e D e r i v a t i z a t i o n involved r e d u c t i o n of sodium a l d u r o n a t e s w i t h s o d i u n b o r o h y d r i d e , l a c t o n i z a t i o n o f t h e r e s u l t i n g a l d o n a t e s , a n d r e a c t i o n w i t h n-propylamine t o form t h e Pj-propylaldonamides. D-Glucuronic a c i d i s t h u s c o n v e r t e d t o

by g . c .

derivatives, respectively.

N-propyl-L-gulonamide.

A l t e r n a t i v e l y , t h e m i x t u r e o f a l d i t o l s and

aldonic a c i d s obtained f r o m t h e borohydride reduction can be s e p a r a t e d on a n ion-exchange

r e s i n i n t h e a c e t a t e form, and t h e

i s o l a t e d a l d o n i c a c i d s l a c t o n i z e d and t r i m e t h y l s i l y l a t e d p r i o r t o g. c

.

analysis.6

A p r o c e d u r e recommended f o r t h e q u a n t i t a t i v e d e t e r m i n a t i o n of

carbohydrates i n s o l u t i o n involved r e d u c t i o n (NaBD4), permethylation (DMSO-NaOH powder - M e I ) , a n d a n a l y s i s by g . c . o r g.c.-m.s.

The

d e r i v a t i z a t i o n c o u l d b e c o n d u c t e d i n t h e same v i a l , a n d i m p r o v e d a c c u r a c y o v e r o t h e r m e t h o d s was c l a i m e d . The m e t h o d was a p p l i e d to

23: Separatory and Analytical Methods

24 5

the analysis of reversion products and anhydroglucoses formed on high temperature dilute acid hydrolysis of cellulose. 7 The OV-17 phase has been found to give improved separation of the diastereoisomeric pertrimethylsilylated methyl 2-(polyhydroxyalkyl)thiazolidine-(4R)-carboxylates formed from enantiomeric pairs of nine aldoses after reaction with L-cysteine methyl ester (c.f. V01.20, p.248). Although each pair of sugar enantiomers gave separate peaks, those from different sugars, e.g., D-xylose and 8 L-arabinose, sometimes co-eluted. An attempt has been made to relate structure to retention in the g.c. of the per-)-trimethylsilyl ethers of the four forms of the four aldopentoses on a variety of packed and capillary columns. 9 Over fifty products , mostly carboxylic acids, from the oxidative and non-oxidative alkaline degradation of L-ascorbic acid have been identified by g.c.-m.s. after conversion to their ammonium salts 10 and pert rj.me thy 1si1y 1at ion. Mono- to tri-saccharides in honey have been identified and assayed by separate analysis of their pertrimethylsilyl ethers before and after formation of oxime derivatives. The dual system was employed to account for overlapping peaks, and sixteen components including two trisaccharides were identified .I1 A good separation of the neutral monosaccharides commonly present in glycoproteins was achieved using their acetylated 2-(pentafluorobenzy1)oxime derivatives, which give peaks f o r syn- and anti-oxime 12 isomers. The e.i.-m.s. of these derivatives was reported. Neutral aldoses from hydrolysis of corn bran residues were analysed as their aldononitrile acetate derivatives.1 3

Thin-Layer Chromatography.- The high performance t.1.c. of monosaccharides and related derivatives, released by hydrolysis of natural and synthetically modified polysaccharide gums, on "low specific area" or "low-activity" silica plates has been reported.14 Unsaturated sulphated disaccharides derived from chondroitin sulphate or proteoglycan by enzymic digestion have been separated on silica gel and quantified by d e n ~ i t 0 m e t r y . l ~Anomers of the purine nucleosides adenosine and deoxyadenosine have been separated on commercial'"chira1 plates", constituted of C18-modified silica treated with copper acetate and (25, 45, 2'E)-4-hydroxy-l-(2-hydroxydodecy1)proline.l6 Other t.1.c. results can be found in the next section, reference 28.

Carbohydrate Chemistry

246 High-Pressure h.p.1.c.

L i q l i d Chromatography.A revipw (34 r e f s . ) on t h e of s u g a r s h a s i n c l u d e d a d i s c u s s i o n o n t h e m e c h a n i s m o f

s e p a r a t i o n o n v a r i o u s s t a t i o n a r y p h a s e s . l7

The g e n e r a l p r i n c i p l e s of p r e p a r a t i v e h . p . 1 . c . o f m o n o s a c c h a r i d e s , s u g a r a c i d s a n d l a c t o n e s , and x - a c e t y l a t e d amino-suEars have been d i s c u s s e d , and many p r a c t i c a l d e t a i l s g i v e n for t h e i s o l a t i o n o f m g t o g q u a n t i t a t e s on e i t h e r a m i n o p r o p y l s i l i c a g e l or c a t i o n e x c h a n g e t 2t t r e s i n s i n t h e H - o r Ca -form.18 The c h a r a c t e r i s t i c s o f H - a n d Ag'-form c a t i o n e x c h a n g e r e s i n , a m i n o p r o p y l s i l i c a g e l , a n d c18r e v e r s e d p h a s e p a c k i n g s for t h e p r e p a r a t i v e h . p . 1 . c . s e p a r a t i o n s o f m a l t o - o l i g o s a c c h a r i d e s h a v e a l s o b e e n c o m p a r e d . l9 A s u b n a n o l i t r e , l a s e r - b a s e d , low c o s t r e f r a c t i v e i n d e x d e t e c t o r h a s b e e n d e s c r i b e d a n d u s e d i n t h e d e t e c t i o n of n a n o g r a m a m o u n t s o f s u g a r s s e p a r a t e d by m i c r o b o r e r e v e r s e d - p h a s e h . p . 1 . c . ( 0 . 2 5 mm i . d . ) . 2 0 A neiv e v a p o r a t i v e l i g h t s c a t t e r i n g d e t e c t o r h a s b e e n d e m o n s t r a t e d i n t h e h . p . 1 . c . a n a l y s i s of mono- a n d o l i g o - s a c c h a r i d e s on a v a r i e t y o f columns (amino-bonded and r e v e r s e d - p h a s e s i l i c a , a n d Ca2'-form r e s i n s ) .21 Selective detection of reducing sugars 2t + e l u t e d f r o m c a t i o n - e x c h a n g e r e s i n s i n t h e Pb -, €I - or Ca2+-form h a s been a c h i e v e d u s i n g a post-column r e a c t o r c o n t a i n i n g i m m o b i l i z e d g l u c o s e d e h y d r o g e n a s e . The e n z y m a t i c o x i d a t i o n of t h e c a r b o h y d r a t e s i s a c c o m p a n i e d by c o n v e r s i o n o f NAD t o NADH w h i c h i s detected electrochemically. G l u c o s e (down t o 2 n g ) , x y l o s e , 2-deoxy-glucose, g l u c o s a m i n e , a n d mannose g a v e g o o d r e s p o n s e s , a n d t h e m e t h o d was a p p l i e d t o t h e d e t e r m i n a t i o n o f g l u c o s e a n d l a c t o s e i n a f e r m e n t a t i o n b r o t h . 2 2 Improved s e n s i t i v i t y (low ng r a n g e ) and s i m p l i c i t y o f s a m p l e p r e p a r a t i o n was a t t a i n e d i n t h e a n a l y s i s o f s u g a r s , e . g . , i n f o o d p r o d u c t s , by e m p l o y i n g p o s t - c o l u m n c a t a l y t i c h y d r o l y s i s ( t o c l e a v e n o n - r e d u c i n g s u g a r s s u c h as s u c r o s e ) a n d 4-aminobenzoic a c i d h y d r a z i d e d e r i v a t i z a t i o n . T h i s d e t e c t i o n p r o c e d u r e was a p p l i e d t o s u g a r s s e p a r a t e d o n Pb2+- a n d Ca2'-form c a t i o n exchange r e s i n s ( e . g . , l a c t o s e and s u c r o s e ) , and r e v e r s e d p h a s e columns ( e . g . , o l i g o s a c c h a r i d e s i n h i g h f r u c t o s e c o r n s y r u p ) . 23 M o n o s a c c h a r i d e s ( R h a , X y l , Ara, G l c , G a l ) r e l e a s e d o n h y d r o l y s i s o f s a p o n i n s h a v e b e e n a s s a y e d by h . p . 1 . c . o n p r i m a r y a m i n e b o n d e d 24 s i l i c a w i t h post-column r e a c t i o n w i t h a l k a l i n e t e t r a z o l i u m b l u e . M o n o s a c c h a r i d e s ( A l l , G l c , Gal, Man) i n p l a n t g l y c o s i d e h y d r o l y z a t e s h a v e b e e n d i f f e r e n t i a t e d by h . p . 1 . c . o n a P b 2 + - f o r m c a t i o n e x c h a n g e r e s i n a t 8 5 0 ~ . * ~A s p a r t o f t h e c h r o m a t o g r a p h i c a n a l y s i s o f p r o d u c t s f r o m t h e h y d r o t h e r m o l y s i s o f p o p l a r wood, s u g a r s a n d t h e i r

23: Separatory and Analytical Methods

247

decomposition products have been analyzed on a Na+-form cation exchange resin.26 Semi-preparative h .p. 1.c. separations of such components, including gluco-oligosaccharides, present in biomass hydrothermolysis solutions have been achieved on polystyrene-based Agf- and Ht-form cation exchange resins , 14C-labelled samples being isolated from 14C-labelled biomass.27 Microgram amounts of neutral sugars could be detected by reductive amination CNaBH CN-(NH4),S041 to produce 1-amino-1-deoxy3 alditols, followed by derivatization with the fluorescent labelling reagent NBD-F (7-fluoro-4-nitrobenz-2-oxa-1,3-diazole), and reversed phase h.p.1.c. analysis. These derivatives were also suitable for t.1.c. analysis on boric acid impregnated silica plates. 28 The glycosylamines formed quantitatively from reducing mono- and oligo-saccharides with 2-aminopyridine have been shown to be suitable derivatives for h.p.1.c. analysis on amino-bonded silica with fluorescence detection. They are stable to storaqe and chromatography, and can be hydrolysed by mild acid to regenerate the original sugar. The procedure avoided the problems encountered in reductive amination with the same amine, and the derivatives had better chromatographic properties. Malto-oligosaccharides up to DP 17 were separated. Glucose gave minor and major peaks f o r aand 6-pyranosylamine derivatives. 29 In the h .p .l.c . of neutral monosaccharides as their 2,4-dinitrophenylhydrazone derivatives on silica, each sugar gave a major (often with a shoulder) and a minor peak. 30 Dansylated derivatives of' glycosyl galactosyl hydroxylysines have been fractionated by reversed-phase h.p.1.c. with fluorescence detection. 31 H.p. 1.c. analysis of perbenzoylated monohexosyl glycolipids (standards and biological samples) on silica pe rmit ted c1as s i ficat ion ac cording t o the ir hydrophoh i c structures.3 2 H . p . 1 . c . of a variety of natural di- and tri-terpene glycosides on a newly developed hard spherical hydroxyapatite has been reported. The hydroxyapatite proved more satisfactory than silica gel €or the normal phase chromatography of water-soluble glycosides due to its greater hydrophilicity. 33 A variety of' on-line h.p.1.c.-m.s. studies have been reported, many using narrow bore (0.22 or 0.26 mm i.d.1 columns. Amongst the samples examined were raffinose and cardenolides ,34 sucrose and adenosine 35 desulphoglucosinolates and the cytokinins zeatin, its riboside and dihydro-analogues ,36 mono- and di-galactosyl diglycerides ,37 and various oligosaccharides including high mannose oligosaccharides from animal urine. 38 39

Carbohydrate Chemistry

248

The h.p.1.c. analyses of malto-oligosaccharides on two new silica-based packings containing bonded polyamine polymer resin or carbamoyl residues have been compared to those achieved on two conventional amine-bonded silica columns over which they display improved stability. Milligram quantiti es of the oligosaccharides neokestose, 1-kestose, 6-kestose and nystose have been isolated by sequential Chromatographic fractionation on amine-modified silica and reversed phase packings, for use as standards in the analysis 41 of sugar cane. A sensitive method for analysis of the constituent monosaccharide components of glycoproteins involved sequential acid hydrolysis, borotritide reduction, re-y-acetylation, and radioactivity detection after separation of neutral alditols and aminoalditols on a cation-exchange resin in the Pb 2t-form at 8OOC.42 A review on the chromatography of glycosaminoglycans and proteoglycans has included a section on the h.p.1.c. analysis of unsaturated disaccharides produced by enzymic hydrolysis.43 Improved separations of unsaturated, mostly sulphated, di- to hexasaccharides from enzymic digestion of various hyaluronic acid, chondroitin sulphate and dermatan sulphate samples have been reported on aminopropyl-bonded silica,44 '45 and cation-exchange resin packings. 46

l-y-(f3-D-Glucopyranosyl)phenobarbital in plasma and bile has been quantified by reversed-phase h .p.1 . c . 47 Improved analysis of organic acids in sugar cane process juice, including 2-, 5-, and 2,5-di-ketogluconic acids, hexonic acids, and glucuronolactone, has been achieved using two cation exchange resins columns in series equilibrated at different temperatures. 48 2-Hydroxyoestrone 2-glucuronide and 4-hydroxyoestrone 4-glucuronide in the urine of pregnant women have been separated and characterized by reversed-phase h .p .I.c 49 Derivatization of glucuronic acid conjugates of phenol, menthol, borneol, testosterone, and estrone with 4-bromomethyl-7-methoxycoumarin (K2C0 -18-crown-6 in acetone) permitted analysis on either normal 3 or reversed-phase columns; derivatives isolated by semi-preparative h.p.1.c. were characterized by direct probe c.i. (NH )-m.~.~' The 3 following reversed-phase assays for ascorbic acid have been reported: in human tears, in connection with an approach to evaluating vitamin C deficiency," as one amongst other goat's milk vitamins using a photodiode array U . V . detector,52 in beer using fatty amines as ion-pair reagents in the eluant and with electro-

.

249

23: Separatory and Analytical Methods c h e m i c a l d e t e c t i o n , 5 3 a n d i n r o s e h i p s a m p l e s w i t h p o s t column

r e d u c t i o n o f d e h y d r o a s c o r b i c a c i d w i t h d i t h i o t h r e i t o l . 54 A s c o r b i c a n d r e l a t e d a c i d s i n human u r i n e have b e e n a s s a y e d on a p o l y v i n y l a l c o h o l g e l u s i n g post-column r e a c t i o n w i t h a f l u o r e s c e n c e r e a g e n t

as d e s c r i b e d e a r l i e r ( s e e V o l . 19, p . 2 4 5 , r e f . 6 3 ) . 55 A s c o r b i c a c i d 2 - p h o s p h a t e i n r e d b l o o d c e l l s a n d p l a s m a h a s b e e n d e t e r m i n e d on a s i l i c a b a s e d anion-exchange

column. 56

Sugar phosphates and n u c l e o t i d e s , p h o t o s y n t h e t i c i n t e r m e d i a t e s on a s t r o n g

e x t r a c t e d from l e a v e s , have b e e n d e t e r m i n e d by h . p . 1 . c . b a s e anion-exchange

r e s i n e l u t e d with a borate-phosphate

c o l o u r i m e t r i c d e t e c t i o n a f t e r post-column sulphuric acid with U.V.-irradiation.

An e x c e l l e n t s e p a r a t i o n o f

a n 1 8 component s t a n d a r d s m i x t u r e was r e p o ~ t e d . ~ ' The s e p a r a t i o n o f m y o - i n o s i t o l and i t s 2 - p h o s p h a t e

e s t e r as

t h e i r f l u o r e s c e n t a n t h r a n i l a t e e s t e r s on r e v e r s e d - p h a s e amine-bonded

b u f f e r and

reaction with orcinol-

o r primary

s i l i c a p a c k i n g s h a s b e e n r e p o r t e d , b u t t h e methodology

seems l e s s t h a n s a t i s f a c t o r y s i n c e i n t h e d e r i v a t i z a t i o n w i t h i s a t o i c a n h y d r i d e n o t a l l hydroxy S r o u p s a r e e s t e r i f i e d , and t h e chromatogram r e v e a l s m i x t u r e s o f p r o d u c t s . 58 Ion-pair reversed-phase h.p.1.c.

a n a l y s i s of a v a r i e t y of

aminoglycoside a n t i b i o t i c s using v o l a t i l e p e r f l u o r i n a t e d carboxylic a c i d s as t h e p a i r i n g i o n s h a s b e e n f u r t h e r

Specific

i o n - p a i r r e v e r s e d - p h a s e a n a l y s e s o f t h e g e n t a m i c i n components i n raw m a t e r i a l a n d p h a r m a c e u t i c a l p r e p a r a t i o n s ,61 a n d o f p i r l m y c i n , a lincosamine-based

a n t i b i o t i c , 6 2 have a l s o a p p e a r e d ,

An improved

procedure f o r t h e fluorescence d e r i v a t i z a t i o n of t h e gentamicins w i t h a - p h t h a l a l d e h y d e p r i o r to r e v e r s e d - p h a s e a n a l y s i s i n v o l v e d a b s 2 r n t i o n o f t h e a m i n o g l y c o s i d e s o n t o s i l i c a g e l , o n t o which was e l u t e d a-phthalaldehyde.

A f t e r a s u i t a b l e r e a c t i o n time e x c e s s

r e a g e n t c o u l d b e washed o f f a n d t h e d e r i v a t i z e d s a m p l e s e l u t e d bJith methanol. 6 3 A number o f p a p e r s on t h e r e v e r s e d - p h a s e

h.p.1.c.

a n a l y s i s of

n u c l e o s i d e s a n d r e l a t e d compounds h a v e a p p e a r e d . Correlations b e t w e e n s t r u c t u r e and r e t e n t i o n t i m e h a v e b e e n drawn f o r a s e r i e s o f a n o m e r i c D-xylo-, n u c l e o s i d e s . 64 '65

D-lyxo-,

D-ribo-

a n d D-arabino-

furanosyl

Absorption isotherms t h a t r e v e a l t h e absorption

b e h a v i o u r o f p e p t i d e and n u c l e i c a c i d c o n s t i t u e n t s , i n c l u d i n g f o u r n u c l e o s i d e s , h a v e b e e n m e a s u r e d by f r o n t a l c h r o m a t o g r a p h y on a m i n i a t u r i z e d h . p . 1.c . s y s t e m r e q u i r i n g o n l y mgs o f s a m p l e . " The f e a t u r e s a s s o c i a t e d w i t h f a s t ( 5 - 1 0 cm column l e n g t h ) , m i c r o b o r e

(1 o r 2 . 1 mm i . d . c o l u ~ n ) ,a n d f a s t - m i c r o b o r e

h.p.1.c.

for the

Curbohy dra re Chemistry

250

s e p a r a t i o n o f n u c l e i c a c i d c o n s t i t u e n t s i n o s i n e , i t s 5'-monophosp h a t e , a n d h y p o x a n t h i n e , as w e l l a s a m i x t u r e o f n u c l e o s i d e s a n d b a s e s , have been s t u d i e d , 6 7 and t h e m o d i f i c a t i o n o f a n e x i s t i n g h.p.1.c.

s y s t e m f o r m i c r o b o r e a n a l y s i s of n u c l e o s i d e s a n d b a s e s

d e s c r i b e d . 68

The s e p a r a t i o n o f n u c l e o s i d e s a n d r e l a t e d compounds

i n 15 min w i t h i s o c r a t i c e l u t i o n e m p l o y e d a n i m p r o v e d column (Select

a),

a n d t h e m e t h o d was a p p l i e d t o t h e a n a l y s i s of' a n i m a l

h e a r t p e r f u s a t e s .69

,Assays h a v e b e e n r e p o r t e d f o r t h e n u c l e o s i d e d r u g s 5 - a z a c y t i d i n e ,7r 2' , 3 ' - d i d e o x y a d e n o s i n e ,71 5 - f l u o r o - 2 ' - d e o x y u r i d i n e , 72 a n d r i b a v i r i n ( 1-8-D-ribofuranosyl-lkJ-1,Z , 4 - t r i a z o l e - 3 c a r b o x a m i d e ) 73y74 i n b i o l o g i c a l f l u i d s a n d t i s s u e s ; i n t h e l a t t e r c a s e a p r e l i m i n a r y c l a s s s e p a r a t i o n on gel-lmmobilized phenylboron-

a t e was u s e d .

The a n a l y s i s o f D N A n u c l e o s i d e s r e l e a s e d by e n z y m i c

h y d r o l y s i s h a s b e e n o p t i m i z e d f o r d e t e r m i n i n g t h e e x t e n t of thymidi n e s u b s t i t u t i o n by 5-iod0-2'-deoxy-uridine.~~ N u c l e o s i d e s , n u c l e o t i d e s a n d b a s e s i n human a n d r a b b i t b l o o d c e l l s w e r e a s s a y e d by r e v e r s e d - p h a s e an i o n - p a i r

h.p.l.c.,

a n d t h o s e i n mouse t u m o r c e l l s by u s i n g

r e a g e n t i n t h e e l u a n t .76

An i o n - p a i r

reversed-phase

m e t h o d was d e t a i l e d for t h e r a p i d a n a l y s i s o f 1 4 C S-adenosylmethionine

-

a n d 3H - l a b e l l e d

77 P y r i d i n e direct liquid

i n enzymic r e a c t i o n m i x t u r e s .

C - n u c l e o s i d o s h a v e b e e n a n a l y s e d by m i c r o b o r e ,

introduction h.p.1.c.-m.s., and semi-preparative d e v e l o p e d for o b t a i n i n g p u r e m a t e r i a l s . 78

h . p . 1 . c . methods

O t h e r column p a c k i n g s h a v e b e e n u s e d i n t h e a n a l y s i s o f nucleosides.

For t h e s e p a r a t i o n o f m i n o r a m o u n t s o f n u c l e o s i d e s w i t h b a s e u n i t s m o d i f i e d by carcinogenic r e a g e n t s , from n o n - m o d i f i e d o n e s , a n h . p . 1 . c . column was e m p l o y e d t h a t h a d a r e a g e n t b o n d e d t o t h e s i l i c a packing which s p e c i f i c a l l y hydrogen-bonded t o normal n u c l e o s i d e s [ a s shown for (1)1 b u t n o t t o t h e m o d i f i e d o n e s . 7 9 The r e t e n t i o n o f n u c l e o s i d e s and b a s e s on a p o l y v i n y l a l c o h o l column u s i n g a m i c e l l a r e l u a n t ( c o n t a i n i n g sodium d o d e c y l s u l p h a t e ) h a s b e e n s t u d i e d , as a f u n c t i o n o f t e m p e r a t u r e , pH a n d c o n c e n t r a t i o n o f d e t e r g e n t . A r e t e n t i o n m e c h a n i s m was p r o p o s e d , a n d t h e m e t h o d o l o g y was e x e m p l i f i e d by a n a l y s i s o f human s e r u m . 8 0 U r a c i l , u r i d i n e a n d f o r m i c a c i d i n e g g p r o d u c t s were a s s a y e d o n a n H+-form c a t i o n exchange r e s i n u s i n g an a c i d i c e l u a n t ; u r a c i l i s a n i n d i c a t o r of d e t e r i o r a t i o n , a n d u r i d i n e a p p e a r s t o b e o n e of i t s p r e c u r s o r s .

a1

I m p r o v e m e n t s h a v e b e e n r e p o r t e d for t h e a n a l y s i s o f a d e n o s i n e a n d i t s n u c l e o t i d e s i n b i o l o g i c a l media u s i n g precolumn d e r i v a t i z a t i o n w i t h bromoacetaldehyde

(to g i v e 1, $ - e t h e n o a d e n o s i n e

a n d a m a c r o r e t i c u l a r anion-exchange r e s i n column. 82

derivatives)

5-Fluoro-2' -

25 1

23: Separutory and Analytical Methods

deoxyuritline has been a s s a y e d in human plasma using precolumn fluorescence derivatization with ~ - b r o m o m e t h y l - 7 - r n e t h y l c o u m a r i n followed by h . p . 1 . c . on silica. 83

OH

Column Chromatography.- A methacrylate-resin column with sugar ligands has been prepared by reaction of an epoxy-activated resin with D-glucamine (i.e., 1-amino-1-deoxy-D-glucitol), maltamine, or lactamine. Stereochemical interaction between immobilized sugar ligands and applied sugar samples was detected in the partition chromatography mode, but not sufficient to separate anomers. On the D-glucamine-resin, a group separation of hexoses from pentoses plus 6-deoxy-hexoses was achieved. 84 An automated analysis of mono-, oligo- and poly-saccharides by anion-exchange chromatography using a borate eluant has employed two post-column reactions, the first hydrolysis with p-toluenesulphonic acid, and the second a reaction with ethanolamine to generate fluorescent products. The method was applied t o determine the sugars in Picea needles, and it was shown that trees damaged by air pollution accumulated free glucose and fructose. 85 a,B-Trehalose, produced as a minor product along with B,B-trehalose by a Koenigs-Knorr glycosylation, has been isolated by anion-exchange chromatography (HO--form resin, H 2 0 as eluant) . 8 6 The preparative separation of six epimeric C-deuterated inositols (scyllo, chiro, neo, allo, muco and epi) was also achieved by anion-exchange Chromatography (boric acid gradient elution) after partial purification by recrystallization. 87 Ion-exclusion chromatography of non-ionic alcohols and sugars has been described, using an H+-form cation-exchange resin, with an acidic eluant and conductivity detection. With dilute sulphuric acid as eluant, sugars gave negative peaks due to a lowering of the solution conductivity by low concentrations of the non-ionic solutes,

252

Carbohydrate Chemistry

b u t w i t h 0 . 1 M b o r i c a c i d as e l u a n t , s u g a r s f o r m e d c o m p l e x e s w h i c h yielded positive responses.

8a

I o n chromatography w i t h o x i d a t i v e amperometric d e t e c t i o n h a s been used t o s e p a r a t e aldehyde-bisulphite

adducts including t h a t of

manno s e . 89 (Bio-Gel P 2 ) of gluco-oligo26 mers f r o m h y d r o t h e r m o l y s i s o f p o p l a r wood has b e e n d e t a i l e d . M e t h y l 2-amino-2,4-dideoxy-B-Da n d L-threo-pentopyranosides The g e l - p e r m e a t i o n

chromatography

h a v e b e e n r e s o l v e d by s e p a r a t i o n o f d i a s t e r e o m e r i c ( + ) - m a n d e l a t e e s t e r s o n s i l i c a . 90

2

Electrophoresis

A m i x t u r e o f 14 n o r m a l a n d m o d i f i e d d e o x y r i b o n u c l e o s i d e s a n d

r e l a t e d n u c l e i c a c i d c o n s t i t u e n t s have been s e p a r a t e d i n less t h a n 40 min b y m i c e l l a r e l e c t r o k i n e t i c c a p i l l a r y c h r o m a t o g r a p h y with

U.V.

detection.

(MECC)

MECC i s a new t y p e o f l i q u i d c h r o m a t o g r a p h y

which employs e l e c t r o o s m o t i c a l l y

pumped m i c e l l e m o b i l e p h a s e s

( i n c o r p o r a t i n g sodium d o d e c y l s u l p h a t e ) , and o f f e r s t h e advantage of b o t h e l e c t r o p h o r e s i s a n d p a r t i t i o n i n g . 91

3

O t h e r A n a l y t i c a l Methods

A l d o s e s c a n b e s e l e c t i v e l y removed f r o m a q u e o u s s o l u t i o n s c o n t a i n i n g ketoses and non-reducing

s u g a r s by r e a c t i o n w i t h a n i l i n e i n t h e

p r e s e n c e o f a c e t i c a c i d as c a t a l y s t , a n d e x t r a c t i o n o f t h e p r o d u c t s by t r e a t m e n t i n s e q u e n c e w i t h e t h e r , e t h y l a c e t a t e , a c t i v a t e d c h a r c o a l , and a c i d i c ion-exchange r e s i n . 92 Certain flavonoids, e.g.,

c a t e c h i n , h a v e b e e n shown t o i n t e r f e r e

i n t h e phenol-sulphuric a c i d c o l o u r i m e t r i c a n a l y s i s of carbohydr-

ates .93 A combined p e r i o d a t e o x i d a t i o n

-

'H-n.m.r.

spectroscopic

technique has been used t o determine t h e s t r u c t u r e o f a v a r i e t y of sugar derivatives, especially those containing terminal d i o l s , and 1 - s u b s t i t u t e d pentopyranoses and t e t r a f u r a n o s e s . 94 A procedure

f o r t h e determination of s u l p h a t e and phosphate i n

s u g a r s u l p h a t e a n d p h o s p h a t e e s t e r s , a n d i n more c o m p l e x g l y c o p r o t e i n s a m p l e s , u s e d h y d r o l y s i s a n d i o n - c h r o m a t o g r a p h y . 95

References 1 K-Berqstroem, J. Pharm. Biomed. Anal., 1986,

4,

609 (Chem. A b S t r . ,

253

23: Separatory and Analytical Methods

2 3 4 5 6 7 8 9 10

11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26

1987, 106,46 628). A.Tacken, H.Brade, P.Kosma, and D.Charon, Carbohydr. Res., 1987, 167, 1. H.Brade, H.Moll, S.R.Sarfati, and D.Charon, Carbohydr. Res., 1987, 167, 291. P.W.Larking, J. Chromatogr., 1987, 420, 231. J.Lehrfeld, J. Chromatogr., 1987, 408, 245. C.Wu and T.Li, Sepu, 1986, fl, 174 (Chem. Abstr. , 1987, 106,43 193) . R.F.Helm, A.H.Connor, and R.A.Young, J. Carbohydr. Chem., 1987, 6, 569. S.Hara, H.Okabe, and K.Mihashi, Chem. Pharm. Bull., 1987, 35, 501. A.Garcia-Raso, 1.Martinez-Castro, M.I.Paez, J.Sanz, J.Garcia-Raso, and F.Saura-Calixto, J. Chromatogr. 1987, 398, 9. K.Niemela, J. Chromatogr., 1987 399, 235. R.Mateo, F.Bosch, A.Pastor, and M.Jimenez, J. Chromatogr., 1987, 410, 319. P.A.Biondi, F.Manca, A.Negri, C Secchi, and M.Montana, J. Chromatogr., 1987, __ 411, 275. H.-P.Li, J. Chromatogr., 1987, 410, 484. B.Mann, J. Chromatoqr., 1987, 407, 369. E.Shimada, N.Kudoh, M.Tomioka, and G.Matsumura, Chem. Pharm. Bull., 1987, 35, 1503. R.S.Feldberg and L.M.Reppucci, J. Chromatogr., 1987, 410, 226. A.Meunier, M.Caude, and R.Rosset, Analysis, 1986, 14,363 (Chem. Abstr., 1987, 106,12 025). K.B.HicksI S.M.Sondey, and L.W.Doner, Carbohydr. Res., 1987, 168, 33. K.B.Hicks and S.M.Sondey, J. Chromatogr., 1987, 389, 183. D.J.Bornhop, T.G.Nolan, and N.J.Dovichi, J. Chromatogr., 1987, 384, 181. M.Lafosse, M.Dreux, and L.Morin-Allory, J. Chromatogr., 1987, 404, 95. G-Marko-Varga,J. Chromatogr., 1987, 408, 157. R.A.Femia and R.Weinberger, J. Chromatogr., 1987, 402, 127. J-Kikuchi, K.Nakamuwa, O.Nakato, and Y.Morikawa, J. Chromatogr., 1987, 403, 319. A.Lenherr, T.J.Mabry, and M.R.Gretz, J. Chromatogr., 1987, 388, 455. E.Burtscher, O.Bobleter, W.Schwald, R.Concin, and H.Binder, J. Chromatogr., 1987. 390. 401. ~G.Bonn, J. Chromatogr., 1987, 397, 393. K.Shinomiya, H.Toyoda, A.Akahoshi, H.Ochiai, and T.Imanari, J. Chromatogr., 1987, 387, 481. G.R.Her, S.Santikarn, V.N.Reinhold, and J.C.Williams, J. Carbohydr. Chem., 1987, 6, 129. N.K.Karamanos, T-Tsegenidis,and C.A.Antonopou1os , J. Chromatogr2, 1987, 405, 221. H.Iwase, I.Ishii, Y.Kato, H.Hamazaki, K.Hotta, A.Umezawa, and T.Kanzaki, J. Chromatogr., 1987, 416, 37. S.Snada, Y.Uchida, Y.Anraku, A.Izawa, M-Iwamori, and Y.Nagai, J. Chromatogr., 1987, 400, 223. R.Kasai, H.Yamaguchi, and O.Tanaka, J. Chromatogr., 1987, 407,205. H.Alborn and G.Stenhagen, J. Chromatogr., 1987, 394, 35. L .Butfering, G .Schmelzeisen-Redeker, and F .W.RGllgen, J. Chromatogr., 1987, 394, 109. F.A.Mellon, J.R.Chapman, and J.A.E.Pratt, , . J 1987, 2,209. H.Y.Kim, J.A.Yergey, and N.Salem, Jr., J. Chromatogr., 1987, 394, 155. S.Santikarn, G.R.Her, and V.N.Reinhold, J. Chromatogr., 1987, 6, 141. Y.Ito, T.Takeuchi, D.Ishii, M.Goto, and T.Mizuno, J. Chromatoqr., 1987, 391, 296. K.Koizumi, T-Utamura, Y.Kubota, and S.Hizukuri, J. Chromatogr.I 1987, 409, 396. P.C.Ivin and M.L.Clarke, J. Chromatogr., 1987, 408, 393. M.Takeuchi, S-Takasaki, N.Inoue, and A.Kobata, J. Chromatogr., 1987, 400, 207. N.B.Beatty and R.J.Mello, J. Chromatogr., 1987, 418, 187. T.Gherezghiher, M.C.Koss, R.E.Nordquist, and C.P.Wilkinson, J. Chromatogr., 1987, 413, 9. J.Macek,J.Krajickovs, and M.Adam, J. Chromatoqr., 1987, 414,156. ~

~

27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45

r

-

,

Carbohydrate Chemistry

254 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84

85 86 87 88 89 90

K.Murata and Y.Yokoyama, J. Chromatoqr., 1987, 415-, 231. V.O.Bharqava, J. Chromatogr., 1987, 419, 421. J.D.Blake, M.L.Clarke, and G.N.Richards, J. Chromatoqr., 1987, 398, 265. K.Shimada, F.Xie, T.Niwa, T.Wakasawa, and T.Nambara, J. Chromatogr., 1987, 400, 215. S.Chakir, P.Leroy, A.Nicolas, J.-M.Ziegler, and P.Labory, J. Chromatoqr., 1987, 395, 553. R.R.Howard, T.Peterson, and R.R.Kast1, J. Chromatoqr., 1987, 414, 434. C.Laviqne, J.A.Zee, R.E.Simard, and C.Gosselin, J. Chromatogr., 1987, 410, 201. J. Chromatoqr., 1987, 405, 347. N.Moll and J.P.Joly, ______ S.J.Zieqler, B.Meier, and O.Sticher, J. Chromatoqr., 1987, 391, 419. T.Seki, Y.Yamaquchi, K.Noguchi, and Y.Yanaqihara, J. Chromatogr., 1987, 385, 287. G.L.Moore and R.M.Fishman, J. Chromatogr., 1987, 419, 95. S.Sawada, M.Kasai, T-Yamada, and T.Takahashi, J. Chromatogr., 1987, 402, 283. M.E.Karqacin, G.Bassel1, P.J.Ryan, and T.W.Honeyman, J. Chromatoqr., 1987, 393, 454. G.Inchauspe, P.Delrieu, P.Dupin, M.Laurent, and D.Samain, J. Chromatoqr., 1987, 404,53. I.De Miquel, E.Puech-Costes, and D.Samain, J. Chromatoqr., 1987, 407, 109. J.H.Albracht and M.S.de Wit, J. Chromatogr., 1987, 389, 306. D.L.Theis, J. Chromatoqr., 1987, 402, 335. R.H.Rumble and M.S.Roberts, J. Chromatoqr., 1987, 419, 408. A.Pompon, G.Gosselin, M.-C.Berqoqne, and J.-L.Imbach, Nucleosides Nucleotides, 1987, 5, 465. A.Pompon, G.Gosselin, M.-C.Bergogne, and J.-L.Imbach, J. Chromatogr., 1987, 388, 113. J.-X.Huang and Cs.Horvsth, J. Chromatoqr., 1987, 406, 275. R.C.Simpson and P.R.Brown, J. Chromatoqr., 1987, 400, 297. R.C.Simpson and P.R.Brown, J. Chromatoqr., 1987, 385, 41. J-Wynants, B.Petrov, J.Nijhof, and H.van Belle, J. Chromatoqr., 1987, 386, 297. A.M.Rustum and N.E.Hoffman, J. Chromatogr., 1987, 421, 387. P.A.Blau, J.W.Hines, and R.D.Voyksner, J. Chromato r., 1987, 420, 1. F.P.La Creta and W.M.Williams, J. Chromatoqr., 198?, 414, 197R.Paroni, C.R.Sirtori, C.Borqhi, and M.G.Kienle, J. Chromatogr., 1987, 420, 189. R.H.A.Smith and B.E.Gilbert, J. Chromatoqr., 1987, 414,202. K.Belanqer, J.M.Collins, and R.W.Klecker, Jr., J. Chromatogr., 1987, 417, 57. A.Werner, W.Siems, H.Schmidt, I.Rapoport, G.Gerber, R.T.Toquzov, Y.V.Tikhonov, and A.M.Pimenov, J. Chromatogr., 1987, 421, 257. J.Vockov2 and V.Svoboda, J. Chromatoqr., 1987, 410, 500. E.L.Esmans, M.Belmans, I.Vrijens, Y.Luyten, F.C.Alderweireldt, L.L.Wotring, and L.B.Townsend, Nucleosides Nucleotides, 1987, 6, 865. B-Feibush, M.Saha, K-Onan, B.Karqer, and R.Giese, J. Am. Chem. SOC., 1987, 109, 7531. Y.-N.Kim and P.R.Brown, J. Chromatogr., 1987, 384, 209. C.E.Morris, J. Chromatogr., 1987, 394, 408. M.Yoshioka, K.Yamada, M.M.Abu-Zeid, H.Fujimori, A,Fuke, K.Hirai, A.Goto, M.Ishii, T.Suqimoto, and H.Parvez, J. Chromatoqr., 1987, 400, 133. H.C.Michaelis, H.Foth, and G.F.Kah1, J. Chromatoqr., 1987, 416, 176. S.Honda, S.Suzuki, and K.Kakehi, J. Chromatogr., 1987, 396, 93. V.R.Villanueva, M.Th.Le Goff, M.Mardon, and F.Moncelon, J. Chromatoqr., 1987, 393, 115. F.W.Parrish, M.M.Meaqher, and P.J.Reilly, Carbohydr. Res., 1987, 168,129. K.Sasaki, F.Balsa, and I.E.P.Taylor, Carbohydr. Res., 1987, 166,171. K.Tanaka and J.S.Fritz, J. Chromatogr., 1987, 409, 271. J.F.Lawrence and C.F.Charbonneau, J. Chromatogr., 1987, 403, 379. G.Anker, J.Attaghrai, D.Pice, apd D.Anker, Carbohydr. Res., 1987, 159,159. ~

255

23: Separatory and Analytical Methods 91 32

93 94 95

K.H.Row, W.H.Griest, and M.P.Maskarinec, J. Chromatogr., 1987, 409, 193. K.Suyama, C.J.Hwang, M.Fujii, and S.Adachi, Anal. Biochem., 1987, 325 (Chem. Abstr. , 1987, 107,20 318) . M.D.Rahman and G.N.Richards, Carbohydr. Res., 1987, 170, 112. S.N.Mikhailov and G.I.Yakovlev, Khim. Prir. Soedin, 1987, 40 (Chem. Rbstr., 1987, 107,59 400). D.N.Ward, T - W e n , and G.R.Bousfield, J. Chromatogr., 1987, 398, 255.

s,

~

Synthesis of Enantiomerically Pure Non-carbohydrate Compounds review has appeared on the use of pyranoid building blocks for natural product synthesis, and the use of 1,2 :5 ,6-di-2-isopropylidene-a-D-glucofuranose for the synthesis of enantiomerically-pure compounds has been surveyed, in German.2

A

Carbocyclic Compounds

1

The cyclopentenone (l), considered to be a versatile chiral intermediate for the synthesis of a variety of natural products, has been prepared from D-ribose as outlined in Scheme 1.3

Reageat6

L,

N a l - M E K ,u..DBU

, UL,

MeO--MeOH

Scheme 1

Annulation of a cyclopentane ring onto a pyranoid template was carried out by free-radical cyclization during a synthesis of 1-a0-methylloganin (2) (Scheme 2); the intermediate ( 3 ) was obtained as a 1:l mixture with its diastereomer, which could be separately c y c l i ~ e d . ~The annulation of a cyclohexene ring on to a furanoid system shown in Scheme 3 produces a model for the oxahydrindene system of the a~erme c t i n s ;the ~ use of this methodology during the

some

BnO

3

2

OBr M9B3rI u,TBDrlSCL-vnt,dazole

DMF , w , O j

,LV

Bu3SnH AION

Scheme 2

construction of the complete system is discussed in Section

4.

257

24: Synthesis of Enantiomerically Pure Non-carbohydrate Compounds

D-Ribose --+ Me0

Reog&

,

,

b, ~ c t - r l & H u,DF3 E t 3 5 . H LU, v ~ , O ~ - zHnO ~ , V L I . ,W L , VUL, ~ PCC

W-&XCJLS&U~Y~~L

bromrde, w , I R A 400 *MeOU, V,L L B H E t 3 A

,U, M o 3 i L S P h LL ,x , M C P B A , XL, Scheme 3

The functionalized cyclohexane ( 4 ) was prepared non-stereospecifically by a route involving two nitroaldol condensations, the carbons of mannose being indicated; this compound has the ring skeleton of histrionicotoxin. Compound ( 5 ) , which constitutes part of the structure of the diterpenoid Taxol-A, has been synthesized in a multistep sequence from L-arabinose (numbering

(4)

(4 )

(5)

1

CHZOBZ

(7)

indicated) .7 A number of compounds of type (6) have been made by cycloadditions of laevoglucosenone, and in the case of (6,X=OAc) , further elaboration led to (7); this is of potential in the synthesis of tetrodotoxin, but the introduction of an aminofunction at the asterisked carbon would be required.9 (S)-5-Hydroxymethyl-2(5H)-furanone ( a ) , derived from D-ribonolactone, was used as an intermediate in a synthesis of the 6acarbocycline analogue (9), with a Pauson-Khand reaction being used to build up the ring system from enyne (10) (Scheme 4 ) . lo When alcohol (8) underwent Diels-Alder reaction with cyclopentadiene, either the (25, 3E)-isomer (11) or its enantiomer could be produced by appropriate manipulation of the initial adduct; face-selective Lewis-acid-catalysed Diels-Alder reactions of a,B-unsaturated esters derived from D-mannitol could be used to produce the (R,R)isomer (12) or its enantiomer. l1 This chemistry was extended to give syntheses of (+)-B-santalene (13) and its enantiomer from (8);I2 the starting material was prepared as described in Vol. 20 p.260, but a number of other papers dealing with routes to this intermediate are mentioned in the next section.

*

Curbohydrate Chemistry

258

The functionalized cyclohexane (14) was produced as the major isomer by [4+2] cycloaddition of a diene derived from D-arabinose (numbering shown) and N-phenylmaleimide. 13 2

r-and 6-lactones

The useful synthon (S)-5-hydroxymethyl-2(5H)-furanone (8) can be obtained crystalline in 40% overall yield from isopropylidene-Dglyceraldehyde,14 and in 48% yield from D-ribonolactone by a new, convenient route.l5 The 5-9-t-butyldiphenylsilyl ether of (8) is accessible fram D-ribonolactone or L-glutamic acid by improved routes (see Vol. 19, p.265) .I6 Lactone (8) was used as an intermediate in the preparation of ( - ) -umbelactone (15)l7 and ( + ) -transcognac lactone (16) from ribonolactone, this latter paper also describing a route from D-ribonolactone to (+)-eldanolide (17).18 The dihydro-derivative of (8) was used as an intermediate in a route to (Z)-B-angelica lactone (18), again from ribonolactone. 19 Degradation of L-ascorbic acid was used to produce (R)-4hydroxytetrahydrofuran-2-one (19); the enantiomer was made from Disoascorbic acid, the chiral centres correspopding with C-5 of the

Do CH20H

* ; '

-C5H,,

Go Go M

CH20Ac

MQ

Me

"51

Q

o

0

-

Me

o

(161

CH2

('7)

(18)

(19)

(20)

precursor. 2o The simple a-methylene lactone (20) has been synthesized from isosaccharinic acid,21 and a full account has been given of the synthesis of the litsenolides referred to last year (Vol. 20, p.261). 22

2 4 : Synthesis of Enuntiomerically Pure Non-carhohydrute Compounds

259

Some ingenious syntheses have been achieved directly from Lascorbic acid; the marine algal metabolite delesserine (21) was prepared in 80% yield by the interaction of 2-2-methyl ascorbic acid with p-hydroxybenzyl alcohol in aqueous solution, and leucodrin (22) was similarly prepared from ascorbic acid and methyl 3hydroxy-3-(p-hydroxyphenyl)propionate, followed by diborane reduction.23 Piptosidin (23) was produced, together with its diastereomer at the methylated carbon atoms, from ascorbic acid and 24 tigloyl cyanide in aqueous solution.

The marine metabolite leptosphaerin (Vol. 20, p.260-61) has been prepared directly by oxidation of the corresponding hemiacetal first prepared from N-acetylglucosamine some years ago (see Vol. 11, p.78) .25 A number of chiral y-lactones have been prepared from D- or L-arabinose, including the Japanese beetle sex pheromone (24) (carbons of D-arabinose indicated) ,26 and (4R, 5I3)-5-hydroxy-4-decanolide, the enantiomer of the proposed autoregulator L-factor, has been synthesized from D-glucose. 27 (-)-Altholactone (25) has been prepared in a ten-step synthesis from D-glucose, involving an interesting Fri,edel-Crafts-type introduction of the phenyl group (Scheme 5); the initial compound illustrated, (26), is the product of a chelation-controlled Reformatsky reaction on the 5 - a l d e h ~ d e . ~Finding ~ that (25) was the enantiomer of the natural antitumour agent, the same workers also prepared the ( + ) - form of altholactone (27), as outlined in Scheme 6; again, a chelation-controlled reaction established the required stereochemistry at C-5 of the first intermediate shown.29 The pyrone anamarine has been prepared in its natural ( + ) form (28) by the chemistry indicated in Scheme 7; the thioacetal (29) was prepared by a known procedure from D-gulonolactone, whilst the phosphonium salt (30) was derived from (R_,R) tartaric acid.30 Prior to this, two groups had reported syntheses of the unnatural (-)-anamarine, both proceeding via the enantiomer of (31), and the enantiomeric ?-ethyl analogue of (30), both derived from glucose. 31t32 Somewhat similar chemistry was used to generate the pyrone

260

Carh ohy d ra te Ch emistry

phm sbo'6' n

Ph

i;w

OBn

BnO

Tsteps,

0

o+-

OH

dH

(27)

Reagents ' i, TsCL ; L, T ~ O H - C ~ H (CHZOH)~ G-

Scheme 6 system of asperlin (32), with the epoxi.de being formed by Sharpless epoxidation of an allylic alcohol. 3 3 (-)-Invictolide (33) has been synthesized in a multistep procedure from laevoglucosan (carbon numbers indicated). 34

L-UL _j.

LV, v

OAc

OAC

0

3

Macrolides and their constituent segments

Yonemitsu's group has given full accounts of their syntheses of methynolide, 35-37 tylonolide,38-39 and pikronolide, 4 0 referred to

,

26 1

24: Synthesis of Enantiomerically Pure Non-carbohydrate Compounds

last year (see Vol. 20, p.261-62); all proceeded ultimately from pglucose and the routes to the different aglycones involved a number of common intermediates and similar chemistry. The same group has also completed a synthesis of (9S)-9-dihydroerythronolide A by linking together glucose-derived fragments previously reported (see Vol. 19 p.263-4) .41 Meanwhile, Kochetkov's group has carried out two syntheses of erythronolide B ( 3 4 ) . In one route, fragments representing C ( 1 ) - C ( 6 ) and C ( 9 ) - C ( 1 3 ) were prepared from laevoglucosan and then linked together (Scheme 8 ) ; in making (35), an epimerization at C ( 5 ) was carried out by base treatment of a precursor of opposite configuration.4 2 Alternatively C ( 5 ) - C ( 9 ) and C ( 1 1 ) - C ( 1 3 ) units were prepared, again from laevoglucosan; the C ( 5 ) - C ( 9 ) unit (36) was extended to ( 3 7 ) using crotyl stannane chemistry, and linked with the other building block ( 3 8 ) via a chelation-controlled aldol reaction (Scheme 8 ) . 4 3 The same group have also reported the syntheses of the C ( 9 ) - C ( 1 3 ) fragments of methynolide and epineomethynolide,4 4 and of neomethynolide.4 5 7

0

0

a, Me

Me

Me

The building-block ( 3 9 ) suitable for the synthesis of amphoteronolide B, the aglycone of the polyene macrolide amphotericin B, was prepared from D-xylose as outlined in Scheme 9 , whilst the enantiomer of (40), made from L-xylose, was used to prepare synthon (41), appropriate for another segment of the same target, by very similar chemistry.46 The chiron (42) which corresponds to the C ( 3 3 ) - C ( 3 7 ) segment of amphoteronolide, was synthesized from

262

Carbohydrate Chemistry C H 20 TB DPS I

1-Xylose

-++

Reagemtts

L,

BCL3

L-(40)

,

-+-+

B

"

*

O +s-i ,, Me0'?+0

OH

OH & )

--++

V

Me0

Ph3P-CH2

Scheme 9

4L:e- k.,) hlcb* Me

CH~OSL?

CH20H

-+-+

___f

Oj-

(43)

Reqents

t>

B~H~-H~o~-oH-

37

Me

Scheme 10

o*

0

O X o (41)

HOOMe

33CH20H

HO

37

Me (42)

the glucose-derived alkene ( 4 3 ) as outlined in Scheme the stereospecificity of the hydroboration is assumed to depend on the presence of a bulky group at C-3, and contrasts interestingly with Yonemitsu's findings in cases with opposite stereochemistry at c-3.

35

Laevoglucosan was used to prepare the hydroxyacid ( 4 4 ) (glucose numbers shown), which was converted into the dimeric macrodiolide, a model for elaiophylin,4 8 and 2-deoxy-D-ribose (numbers indicated) was used to prepare the chiral building-block ( 4 5 ) for one segment of boromycin. 4 9

4

Spiroacetal systems

series of full papers have detailed the synthesis of fragments of the marine toxin okadaic acid,50-52 and the linkage of the parts to achieve the total enantiospecific and stereoselective synthesis of this complex natural product containing three spiroacetal units and 53 17 chiral centres. In a total synthesis of avermectin A l a , the spiroketal unit ( 4 6 ) was prepared as outlined in Scheme 11, involving an interesting stereospecific 'carba-Ferrier' reaction, and a chelationcontrolled hetero-Diels-Alder cycloaddition as key steps. 54 InterA

24: Synthesis of Enantiomerically Pure Non-carbohydrate Compout1d.y

263

mediate (46) was extended at the primary alcohol function, and then linked with the 'southern zone', the synthesis of which54 paralleled that indicated earlier in Scheme 3 , followed by macrolactonization. The methodology for spiroacetal formation had been previously evaluated in a simpler model system.55 The completion of the synthesis by attachment of the disaccharide unit to the aglycone is mentioned in Chapter 3 .

pLvo

6

+

P

L

V

o

a

Me

l=/SLPh3

i"'

I"

OPlV

O

H S-

~~

H

OPW

opw

CHO

Ho-,+-r Reqer&s

L,

H2 Pd/C,

u , LLCuMez

, tu,D a m s h + k y k

&me M3Br2, w, H9O-12- C C L 4 , v, LLOW- MeOH/THF

S c h e m e 11

The spiroacetal portion of milbemycin E (47) has been synthesized in 13 steps from methyl a-D-glucopyranoside, via the known dichloride ( 4 8 ) , as indicated in Scheme 12. 56

OAc

~

n

T (J OH

OMe OAc

U-LV

__+

OM€.,

OH

(4 8) Reageds'

5& 0

x ye

'

"-u

E:

Me

Me

:

OS+

,

L, Hz-P&/C- K O H - I I - ~ O H ; iL, H S ( C ~ ~ ) ~- SHCL H 'Li, M e 2 t O - C u S 0 , - T s O H ,

W,NOLJY-EK)H ; v, CW,:CHM9Qr--CuL

i vi, h-BuLi

;VU,

LAH;V~,M~l(O-T~OH;

OH

ix, t - C u L i , Lhen RL

(47)

S c h e m e 12

The fructose derivative ( 4 9 ) has been used to prepare the chiral trioxaspiroundecane (50), an oxa-analogue of the olive fruit fly pheromone, as outlined briefly in Scheme 13.57 During a total synthesis of the spiro-acetalpolyether antibiotic salinomycin, the chiron (51), representing the middle section of the target, was prepared from D-glucose (numbers indicated), whilst (52) and (53) were synthesized from glucose and isopropylidene D-glyceraldehyde respectively, and linked to form ( 5 4 ) representing the right-hand end: the route to (53) involved an inversion of configuration at C-2

2 64

Curboh y d rate Chemistry

of D-glyceraldehyde, the other chiral centres being derived from malic acid.58

OH

V

(491 S c h e m e 13

( 521

(51)

5

(54)

Other Oxygen Heterocycles

A review on synthetic routes to polyether antibiotics covers a number of procedures involving carbohydrate synthons.59 Hanessian's group have used the concept of the 'replicating butenolide template' to prepare a chiral fragment (55) of the polyether antibiotic ionomycin as outlined in Scheme 14.16 CHzOTBDPS

b1

3

o

-

+;a Me

-OI;;

CH20H

r o + : : i

Me

0

Scheme 14

(55)

(57)

2-Deoxyribose was used as precursor for both chiral segments of (5S)-5-hydroxy-14,15-LTA4 (56), the biogenetic precursor of the lipoxins (sugar numbers indicated) ,6o and the carbons of D-xylose were incorporated as indicated into the salt marsh caterpillar moth pheromone (57).61 The fungal toxins AK-I1 and AF-IIC (58) have 62 been synthesized from L-ascorbic acid. When the chiral unit (59), produced via the diastereoselective addition of methyl magnesium bromide to isopropylidene D-glyceraldehyde, was manipulated as indicated in Scheme 15, (+)-muscarbe

265

24: Synthesis of Enantiomerically Pure Non-carbohydrate Compounds

(60) was obtained; use of the enantiomer of (59), obtained from Dglucose (the methyl group corresponding with C-6 of glucose) gave ( - ) -muscarhe. 63 Another route to (+) -muscarine (60) and (+) epimuscarine (epimer at the secondary alcohol) involves the manipulation of (61) (c.f.Vol. 18, p.34; see also Chapter 3 ) .64 The mycotoxin (-)-botryodiplodin (62) was obtained via conjugate addition of a complex cuprate to the unit (63) reported last year (Vol. 20, p.266) and the same chemistry was also carried out in the enantiomeric series.65 A new route to (+)-oxybiotin (64) has been

*C H ~ O H (59)

.

reported, starting from D-xylose (sugar carbons numbered) 66 A full account has been given of Curran's synthesis of pseudomonic acid involving a Claisen rearrangement of a glycal derivative (see Vol. 18, p.247), together with further examples of such reactions and interesting observations and rationalizations concerning the relative rates of such processes. 67 The absolute configuration of bissetone, from a gorgonian coral, has been established as shown in (65) by a synthesis (Scheme 16) from Dglucose via the enone (66) which was obtained by an improved procedure.68

In synthetic studies directed towards the complex polyether systems of the halichondrins, a C(1) - C(15) unit (67) has been synthesized as outlined in Scheme 17. In this Scheme, the formulae shown are of the absolute chirality appropriate for the halichondrins, but the work was carried out using D-galactose as starting

Carbohydrate Chemistry

266

material; this was converted into the enantiomer of (68) via the 3,4-acetonide of 1,6-anhydrogalactose. The reaction of (68) with allyltrimethylsilane and BF3 ensured the correct stereochemistry at 69 C-1 of the sugar (axial reagent approach).

DnO

(68)

~~

S c h e m e I7

Both enantiomers of endo-brevicomin have been synthesized from the D-ribose derivative (69), prepared from the sugar in 4 steps, by appropriate manipulation of the two ends of the chain; the ( + ) isomer (70) was shown to be the natural pheromone of the southern pine beetle (Scheme 18) .70 The pheromone (-)-frontalin (71) has Et

0Bn OBn

+ -,-

0Bn

+-)

OBri

(69)

Scheme 18

been made from a-D-isosaccharinolactone (72) (sugar numbers indicated) in 17% overall yield. 71 The intramolecular Friedel-Crafts-type reaction shown in Scheme 19 has been accomplished, albeit in low yield, as a model for the attachment of the amino-sugar unit to the anthraquinone core of nogalamycin. 72 6

Nitroaen heterocvcles

full account has been given of one of the syntheses reported last year (V01.20 p.268) of unnatural (-)-sesbanimide A from D-sorbitol,

A

24: Synthesis of Enantiomerically Pure Nopi-carbohydrate Compounds

267

and these workers have also prepared the (+)-isomer from D-xylose in a manner very similar to other groups (see Vols. 19 and 20). 73 The synthesis of chiral hydroxylated pyrrolidines, piperidines, and indolizidines continues to attract attention. The synthon (73) can be prepared stereospecifically from the E-alkene (74) as outlined in Scheme 20; the 5-alkene, produced together with (74) by Wittig reaction with 2,3-g-isopropylidene- 2-erythrose, gave, by the same sequence of reactions, the C-2 epimer of (73) .74 The same group has given a full account of other routes to synthons such as

(73) (see Vol. 18, p.256), and their use in the preparation of pyrrolizidine alkaloids such as retronecine.and crotanecine. 75 Full papers have appeared giving details of the syntheses by Fleet's group of ( 2 R , 35, 4 R ) - 3 , 4 - d i h y d r o ~ y p r o l i n e , ~(2R, ~ 3R, 4R, 5g)-trihydroxypipecolic acid, its (2g)-isomer, and (2R, 3E, 4R)3,4-dihydroxyproline,77 (25, 45, 5s)-dihydroxypipecolic acid and bulgechine (see Vol. 20, p. 267-68) ,78 1,4-dideoxy-l,4-imino-Dmannitol (Vol. 18, p.168), 1,4-dideoxy-1,4-imino-D-lyxitol (Vol. 19, p.170), and swainsonine (Vol. 18,~.253).~' The same group has also described the synthesis of 1,4-dideoxy-1,4-imino-L-gulitol (75), 1,4-dideoxy-1,4-imino-D-lyxitol (76), and (-)-8-epi-swainsonine (77),*O by methods similar to those used earlier by Suami's group for the synthesis of (77) (Vol. 20, p.267), and the Japanese workers have given a full account of their synthesis of (-)-8a-episwainsonine (Vol. 20, p.267). 81 A new route to castanospermine (78) involves as a key step the

Carbohydrate Chemistry

268

diastereoselective addition of ally1 trimethylsilane to the aldehyde (79), produced by oxidation of a previously-reported intermediate (Vol. 19, p.170); the analogous manno- and galactoprecursors gave rise to 8- and 6-epi-castanospermine, and the authors claim that natural 6-epi-castanospermine is the enantiomer of the material prepared. 82 1-Deoxycastanospermine (80) has been prepared from D-glucose via the key intermediates shown in Scheme 21; the product was not an effective glucosidase inhibitor, indicating the need for the 1-hydroxy group for the efficacy of castanospermine itself.83 The same workers have also devised routes from D-glucose to (6F3, 72, 8aR)-dihydroxyindolizidine (81) and(6R, 7?, 85 8aR)-trihydroxyindolizidine (82) (glucose numbering exocyclic), involving ring-closure between N-2 and C-6 of a 2-

&ao 6

CH20H

Y y H Z2N 3

6Stqs

bCH2

5

Ph

4-

R e t q e n t : L, NBs

*

bo

(CH2

-L=

l3Ng

> *,, ORz

x.. HO$

2

H-

OH

o+-

o+

sw5

o\\*.

NJ (00)

Scheme 21

HO

HO

A c H OHN ~ 0 2 H b

(81) R = H

(92) R = OH

amino-2-deoxy-D-altrose derivative as the key step.84 The pipecolic acid derivative (83) has been synthesized as a potential sialidase inhibitor; the route proceeded from D-glucosamine via intermediate (84), which was cyclized between N-2 and C-6, and nitrogen introduced at C-5 with inversion of configuration.85 In

269

24: Synthesis of Enantiomerically Pure Non-carbohydrate Compounds

certain cases, when diaziridines of type (85) (Vol. 20, p.271) are treated with nucleophiles X-, piperidines of type (86) are produced. 86 Some other papers dealing with hydroxylated nitrogen heterocycles are mentioned in Chapter 18. The p-lactam (87) has been prepared by a route analogous to 87 that reported for a similar case last year (Vol. 20, p.268-9), and the glycal cycloadduct (88) (c.f.Vol. 20, p.268-9) was subjected to the chemistry outlined in Scheme 22 to give products of potential use in the synthesis of 1-oxapenem and 1-oxacephem systems.88

R e a c ~ e n t s :L, N a l O 1 , ; u, NaBH4 ;h,NaHCO3

Scheme 22

7

Acyclic Compounds

Octadecane -1,2,3,4-tetraols of D-lyxo, L-ribo and L-xylo configurations have been synthesized by Wittig elongation of aldehydo-pentose derivatives; the natural product guggultetrol-18 was shown to have D-xylo- config~ration.~~ Similar work by others was reported last year (Vol. 20, p.271-72). A full account has been given of the synthesis of ( + ) - and ( - ) - indicine -E- oxides (see Vol. 20, p.271) by linking chiral pyrrolizidines with chiral carboxylic acids derived from D- or L- arabinose; the diastereomeric intermedine- N-oxides were also prepared. The synthon (89), representing the acyclic portion of the aureolic acid antibiotics, has been prepared from D-glucose, with an inversion of configuration at c-4.91 A number of chiral building-blocks such as (90) and (91) can be prepared via the zinc-copper cleavage of 5-bromo-5-deoxy-2,30-isopropylideneribonolactone (see Vol. 20, p.272), 92 and in the case of (90) the optical purity via this method was found to be

I

(90)

(91)

J

(92)

superior to that of material prepared by Sharpless epoxidation of divinyl carbinol.93 D-Mannitol has been converted into the g,g-

Carbohydrate Chemistry

270

synthon (92),94 and both E- and 2- isomers of a-hydroxy-B-aminopropionaldehyde and -propionic acid have been made from D-mannitol by appropriate manipulation of 1,2 : 5,6-diepoxides, followed by central oxidative cleavage.95 The D-mannitol derivative (93) can be used to provide optically-active glycerol derivatives in either enantiomeric series, the products being known precursors of platelet-activating factor (Scheme 23) ,96 and various fluorinated analogues of the factor (94) have been prepared from 3-9-benzyl1,2-C)-isopropylidene-D-threitol. 97 A range of 2,3-9-diprotectedD-glyceraldehyde derivatives have been synthesized from D-mann99 itol,98 as have various ( 5 )-l-alkylamino-3-aryloxy-2-propanols; the absolute configuration of a compound of this class, ( + ) celiprolol (95) has been established as ( E ) - by a synthesis from 100 isopropylidene-D-glyceraldehyde. CH20H

k::;H2rQoMe

o:m Meoal

A+

L-UL

+

(93)

Rea9e.ak

L!

CHzOR p

n

CH20H

OM e

B n @ r - N a H ,L, N a B H 3 C N - T F A 1 U L , N a T O 4

, N%bHi+

S c h e m e 23

Papers covering the use of carbohydrates as chiral auxiliaries in enantioselective syntheses are mentioned in Chapters 6 , 7 , and 10.

References F.W. Lichtenthaler, Nat. Prod. Chem., Proc. Int. Symp-. Pak.-U.S. Binatl. Workshop, 1 s t 1984 (Pub. 1986) 227-(Chem. Abstr., 1987, 107, 134048), GIT Fachz. Lab., 1986, ~ , - 1 1 0 9 ,1112 (Chem. Abstr., 1987, 107, 237126). H. Ohrui, M. Konno, and H. Meguro, Agric. Biol. Chem., 1987, 51, 625. H. Hashimoto, K. Furuichi, and T . Miwa, J. Chem. SOC., Chem. Zmmun., 1987,

w,

1002. D.M. Armistead and S.J. Danishefsky, Tetrahedron Lett., 1987, 28, 4959. K. Brewster, J.M. Harrison, T.D. Inch, and N. Williams, J. Chem: SOC.,

Perkin Trans. I, 1987, 21. L. Pettersson, T. Frejd, and G . Magnusson, Tetrahedron Lett., 1987, 28, 2753. M. Isobe, N. Fukami, T. Nishikawa, and T . G o t o , Heterocycles, 1987, 22, 521.

271

24: Synthesis of Enantiomerically Pure Nort-carbohydrate Cornpounds 9 10

11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

M. I s o b e , T. Nishikawa, S . P i k u l , and T . Goto, T e t r a h e d r o n L e t t . , 1987, 8 , 6485, P . Magnus and D.P. B e c k e r , J . Am. Chem. SOC., 1 9 8 7 , 7495. S. Takano, A . K u r o t a k i , and K. Ogasawara, S y n t h e s i s , 1987, 1075. S . Takano, K. Inomata, A . K u r o t a k i , T . Ohkawa, and K . O g a s a w a r a , J . Chem. _-S O ~ . ,Chem. Commun., 1987, 1721. A . B . R e i t z , A . D . J o r d a n , and B . E . Maryanoff, J . Org. C h E . , 1987, 4800. B. HYfele and V. J g g e r , L i e b i g s Ann.Chem., 1987, 8 5 . J . A . J . M . Vekemans, G.A.M: F r a n k e n , G. J . F . C h i t t e n d e n , and E.F. G o d e f r o i , T e t r a h e d r o n L e t t . , 1987, 2293. S . H a n e s s i a n and P . J . Murray, T e t r a h e d r o n , 1987, 5055. R.M. O r t u n o , J . B i g o r r a , and J . F o n t , T e t r a h e d r o n , 1987, 2199. R.M. O r t u n o , R . Merce, and J . F o n t , T e t r a h e d r o n , 1987, 4497. R.M. O r t u n o , D. Alonso, J . C a r d e l l a c h , and J . F o n t , T e t r a h e d r o n , l 9 8 7 , 2191. A . Tanaka and K . Y a m a s h i t a , S y n t h e s i s , 1987, 571. K . Bock, I . M . C a s t i l l a , I . L u n d t , and C . P e d e r s e n , A c t a . Chem.- Scand. S e r . B , 1987, 13. W.W. Nood and G.M. Watson, J . Chem. SOC., P e r k i n T r a n s . 1 , 1987, 2681. A . J . P o s s and R . K . B e l t e r , T e t r a h e d r o n L e t t . , 1987, 2555. A . J . P o s s and M.S. Smyth, T e t r a h e d r o n L e t t . , 1987, 28, 5669. P. R o l l i n , T e t r a h e d r o n L e t t . , 1987, 3813. Y. N i s h i d a , M. Konno, H . H o r i , H . O h r u i , and H. Meguro, A g r i c . B i o l . 1987, 635. 165, I J . S . Yadav, B.V. J o s h i , and M.K. G u r j a r , Carbohydr. R e s . , 1987, J . - P . Gesson, J . - C . J a c q u e s y , and M. Mondon, T e t r a h e d r o n L e t t . , 1987, 3945, J . - P . Gesson, J.--C. J a c q u e s y , and M. Mondon, T e t r a h e d r o n L e t t . , 1 9 8 7 , 3949. K. Lorenz and F.W. L i c h t e n t h a l e r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6437. L e t t . , 1987, F.W. L i c h t e n t h a l e r , K . L o r e n z , and--hedron 47. S. V a l v e r d e , A. Hernandez, B . H e r r a d o n , R.M. R a b a n a l , and M. Martin-Lomas, T e t r a h e d r o n , 1987, 3499. S. V a l v e r d e , B. Herra.don, R.M. R a b a n a l , and M. Martin-Lomas, Can. J . Chem. 1937, 339. T. Wakamatsu, Y . N i s h i k i m i , H. K i k u i r i , H. Nakamura, and Y. Ban, H e t e r o c y c l e s , 1987, 26, 1761. Y . Oikawa, T. Tanaka, K. H o r i t a , I. Noda, N . Nakajima, N . Kakusawa, T. Hamada, and 0. Yonemitsu, Chem. Pharm. B u l l . , 1987, -35, 2184. Y . Oikawa, T. Tanaka, T. Hamada, and 0. Yonemitsu, Chem. - Pharm. B u l l . , 1987, 35, 2196. T. Tanaka, Y . Oikawa, N. Nakajima, T . Hamada, and 0. Yonemitsu, Chem.Pharm. B u l l , , 1987, 35, 2203. T. Tanaka, Y . Oikawa, T. Hamads, and 0. Yonemitsu, Chem. Pharm. B u l l . , 1987, 2209. T. Tanaka, Y. Oikawa, T. Haxrada, and 0. Yonemitsu, Chem. Pharm. B u l l . , 1987, 35, 2209. N . Nakajima, T. Tanaka, T. Hamada, Y . Oikawa, and 0. Yonemitsu, Chem. Pharm. B u l l , , 1987, 2228. H. Tone, T . N i s h i , Y . Oikawa, M , H i k o t a , and 0. Yonemitsu, T e t r a h e d r o n L e t t . , 1987, 4569. -A.F. S v i r i d o v , M.S. Ermolenko, D.V. Yashunsky, V.S. B o r o d k i n , and N . K . Kochetkov, T e t r a h e d r o n L e t t . , 1987, 3835. A.F. S v i r i d o v , M.S, Ermolenko, D . V . Yashunsky, V.S. B o r o d k i n , and N.K. Kochetkov, T e t r a h e d r o n L e t t . , 1987, 2 8 , 3839. A.F. S v i r i d o v , D.V. Y a s h u n s k i i , M. S . E r m o i e n k o , V. S. B o r o d k i n , and N.K. Kochetkov, Izv. Akad. Nauk SSSR, S e r . Khim., 1986, 2566 (Chem. A b s t r . , 175726). 1987, A.F. S v i r i d o v , D.V. Y a s h u n s k i i , d.S. Ermolenko, V.S. B o r o d k i n , and N . K . Kochetkov, g v . Akad. Nauk SSSR., S e r . Khim., 1986, 2571 (Chem. A b s t r . , 1987, 175727).

109,

2,

22,

43,

33 34 35 36 37 38

39 40

41 42 43 44

S,

8,

1,

2,

g,

35,

35,

2,

28,

107,

45

43.

-

41,

I I

32

42, 44,

107,

8,

Carbohydrate Chemistry

272 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80

81 82 83

K . C . N i c o l a o u , R.A. Dailies, J. U e n i s h i , W.S. L i , D.P. P a p a h a t j i s and T.K. C h a k r a b o r t y , J . Am. Chem. S O C . , 1987, 2205. D. Liang, A . D . Schuda,and B . F r a s e r - R e i d , Carbohydr. R e s . , 1987, 229. T . Wakamatsu, S. Yamada, H. Nakamura, and Y. Ban, H e t e r o c y c l e s , 1987, 25, 43. R.M. S o l 1 and S.P. S e i t z , T e t r a h e d r o n L e t t . , 1987, 5457. Y . I c h i k a w a , M. I s o b e , 9.-L. B a i , and T . Goto, T e t r a h e d r o n , 1987, 4737. Y . Ichikawa, M. I s o b e , and T . Goto, T e t r a h e d r o n , 1987, 4?_, 4749. Y . Ichikawa, M. I s o b e , H. Masaki, T . K a w a i , and T . Goto, T e t r a h e d r o n , 1987, 43, 4759. M. I s o b e , Y. I c h i k a w a , D.-L. B a i , H. Masaki, and T. Goto, T e t r a h e d r o n , 1987, 4767. S.J.Danishefsky, D.M. A r m i s t e a d , F.E. W i n c o t t , H.G. S e l n i c k , and R. Hungate, J , Am. Chem. S O C . , 1987, 8117. F.E.Wincott, S . J . D a n i s h e f s k y , and G . S c h u l t e , T e t r a h e d r o n L e t t . , 1987, 8, 4951. G. Khandekar, G . C . Robinson, N.A. S t a c e y , P.G. S t e e l , E . J . Thomas, and S . V a t h e r , J. Chem. S O C . , Chem. Commun., 1987, 877. K.H. Aamlid, L. Hough, A . C . R i c h a r d s o n , and D. Hendry, C a r b o h y d r . R e s . , 1987., 164., 373. K . H o r z , S . Nagato, Y . Oikawa, and 0 . Yonemitsu, T e t r a h e d r o n L e t t . , 1987, 2 8 , 3253. T.L.B. B o i v i n , T e t r a h e d r o n , 1987, 3309. Y . L e b l a n c , B . J . Fitzsimmons, J. Rokach, N . Ueda, and S. Yamamoto, T e t r a h e d r o n L e t t . , 1987, 28, 3449. J . R . Pougny and P. R o l l i n , T e t r a h e d r o n L e t t . , 1987, 2977. H. I r i e , K . Matsumoto, T. Kitagawa, Y. Zhang, T . Ueno, T . Nakashima, and H. Fukami, Chem. Pharm. B u l l . , 1987, 2598. J . Mulzer, A. Angermann, W. Munch, G . S c h l i c h t h 8 i - 1 , and A.Hentzsche1, L i e b i g s Ann. Chem., 1987, 7 . A. Bandzouzi and Y . C h a p l e u r , J . Chem. SOC., P e r k i n T r a n s . I , 1987, 6 6 1 . N . Rehnberg, T. F r e j d , and G . Magnusson, T e t r a h e d r o n L e t t . , 1987, 3589. D. M i l j k o v i c , V . P o p s a v i n , arid J . H a r a n g i , T e t r a h e d r o z t t . , 1987, 5733. D.P. C u r r a n and Y.-G. Suh, Carbohydr. R e s . , 1987, 161. M. Brehm, W.G. Dauben, P. KBhler, and F.W. L i c h t e n t h a l e r , Angew. Chem., I n t . Ed. E n g l . , 1987, 1271. T.D. A i c h e r and Y . K i s h i , T e t r a h e d r o n L e t t . , 1987, 3463. H . R e d l i c h , W. Bruns, W . F r a n k e , V. S c h u r i g , T.L. Payne, and J . P . V i t e ' , T e t r a h e d r o n , 1987, 43, 2029. M.-C. T r i n h , J.-C. F l o r e n t , and C . Monneret, J . Chem. S O C . , Chem. Commun., 1987. 615. T.H. Smith and H . Y . Wu, J. Org. Chem., 1987, 52, 3566. M.J. Wanner, N.P. W i l l a r d , G.-J. Koomen, and E.-K. P a n d i t , T e t r a h e d r o n , 1987, 43, 2549. J . G . Buchanan, A . R . E d g a r , and B . D . H e w i t t , J . Chem. S o c . , P e r k i n T r a n s . I , 1987, 2371. J . G . Buchanan, V . B . J i g a j i n n i , G . S i n g h , and R.H. Wightman, J . Chem. S O C . , P e r k i n T r a n s . I , 1987, 2377. P.U. B a i r d , J . C . Dho, G . W . J . F l e e t , J . M . Peach, and K. P r o u t , J. Chem. SOC. P e r k i n T r a n s . I, 1987, 1785. B.P. B a s h y a l , H.-F. Chow, L.E. F e l l o w s , and G . W . J . F l e e t , T e t r a h e d r o n , 1987, 43, 415. B.P. B G h y a l , H.-F. Chow, and G . W . J . F l e e t , T e t r a h e d r o n , 1987, 423. B.P. B a s h y a l , G . W . J . F l e e t , M . J . Gough, and P.W. Smith, T e t r a h e d r o n , 1987, 43, 423. G . N . A u s t i n , P.D. B a i r d , G . W . J . F l e e t , J . M . Peach, P.W. S m i t h , and D . J . Watkin, ~T e t r a h e d r o n , 1987, i 3 - , 3095. K . - i . Tadano. Y . H o t t a . M. M o r i t a . T. Suami. B , W i n c h e s t e r , and I . C . d i B e l l o , Bull.-Chem. Soc: J p n . , 1 9 8 i , 60, 3667. H. Hamana, N . I k o t a , and B. Ganem, J T O r g , Chem., 1987, 52, 5492. D. Hendry, L. Hough, and A.C. R i c h a r d s o n , T e t r a h e d r o n L e t t . , 1987, 28, 4597.

109,

164,

8,

_42,

42,

2,

42,

8,

2,

8, 2,

171,

6,

28,

5,

24: Synthesis of Enantiomerically Pure Non-carbohydrate Compounds 84 85 86 87 88 89 90 91 92 93 94

95 96 97 98 39

D. Hendry, L. Hough, and A.C. R i c h a r d s o n , T e t r a h e d r o n L e t t . , 1987, 22, 4601. K. C l i n c h , A . V a s e l l a , and R. S c h a u e r , T e t r a h e d r o n L e t t . , 1987, 6425. A . D u r c a u l t , I. T r a n c h e p a i n , C . Greck, and J . - C . Depezay, T e t r a h e d r o n L e t t . 1987, 3341. I . P a n f i l , C. B e l z e c k i , and M. Chmielewski, J . Carbohydr. Chem., 1907, 463. M. Chmielewski, Z . K a l u z a , W . Abramski, and C. B e l z e c k i , T e t r a h e d r o n L e t t . , 3035. 1987, 5933, V . Kumar and S. Dev, T e t r a h e d r o n , 1987, Y . N i s h i m u r a , S. Kondo, T. T a k e u c h i , and H. Umezawa, B u l l Chem. SOC. J p n . , 1987,.~60, 4107. A.V.R.Rao, T.G.M. Dhar, M.K. G u r j a r , and J . S . Yadav, I n d i a n J. Chem., S e c t . B , 1986, 999 (Chem. A b s t r . , 1987, 175 7 2 9 ) . V. J s g e r and B. H s f e l e , S y n t h e s i s , 1987, 801. B. Koppenhoefer, M. Walser, D . S c h r u t e r , B. H g f e l e , and V. J 3 g e r , T e t r a - . h e d r o n , 1987, 43, 2059. M.K. G u r j a r and S.M. Pawar, I n d i a n J . Chem., S e c t , B , 1987, =,55 (%. A b s t r . , 1987, 237 1 7 1 ) . -A. D u r e a u l t , I. T r a n c h e p a i n , and J . C . Depezay, S y n t h e s i s , 1 9 8 7 , 491. U. P e t e r s , W. Bankova, and P , W e l z e l , T e t r a h e d r o n , 1 9 8 7 , 3803. K. F u j i t a , S. Kobayashi, I . Kudo, K. I n o u e , S. Nojima, M. Ohno, Y . Kobayashi, M. O d a g i r i , and '1. T a g u c h i , Chem. Pharm. B u l l . , 1987, 647. J . J u r c z a k , T. Bauer,and M. C h m k l e m k i , C a r b o h y d r . Res., 1987, i 6 5 , 493. B. Lamm, K. Ankner, and M. F r a n t s i , A c t a Chem. S c a n d . , S e r d . , 1 9 8 7 , 202 0. H o f e r and K. S c h l o e g l , Arzneirn.-Forsch., 1986, 36, 1157 (Chem. A b s t r . , 1987, 214 2 4 9 ) .

8,

28,

5,

2,

2,

z,

107,

107,

43,

-

I

100

273

106,

2, 5,

Author Index I n t h i s i n d e x t h e number g i v e n i n p a r e n t h e s i s i s t h e C h a p t e r number of t h e c i t a t i o n and t h i s i s f o l l o w e d b y t h e r e f e r e n c e number o r numbers o f t h e r e l e v a n t c i t a t i o n s w i t h i n t h a t Chapter

A a m l i d , K.H. ( 1 0 ) 3 8 ; ( 2 4 ) 57 Abagyan, G.V. ( 2 ) 5 1 ; ( 2 2 ) 102 Abbas, S.A. ( 3 ) 67, 7 2 , 7 3 ; ( 4 ) 20, 28; ( 7 ) 5 7 ; ( 8 ) 7 ; ( 1 5 ) 9 , 10 A b b a t e , S. ( 2 2 ) 2 Abdel-Malik, M.M. ( 5 ) 2 7 ; ( 2 1 ) 23 A b d u l a z i z , M.A. ( 1 2 ) 17 Abe, F. ( 1 5 ) 2 Abe, Y. ( 8 ) 2 5 ; ( 1 3 ) 9; ( 1 6 ) 56 A b i d o v a , M.F. ( 1 8 ) 10 A b o l a , J. ( 2 2 ) 32 A b r a m s k i , W. ( 1 3 ) 7 ; ( 2 4 ) 88 Abronin, I.A. ( 2 ) 5 Abu-Zeid, M.M. ( 2 3 ) 82 Achiwa, K. ( 3 ) 8 7 , 8 9 , 91, 9 6 ; ( 5 ) 15; ( 7 ) 43-46; ( 9 ) 60-64 A d a c h i , K. ( 1 9 ) 4 3 , 75 A d a c h i , S . ( 2 3 ) 92 Adam, M. ( 2 3 ) 45 A d l g a s s e r , K. ( 1 1 ) 22 A f a n a s ' e v , V.A. ( 2 ) 5 ; (10) 14; (14) 19; (22) 16 A f t a n i , M. ( 5 ) 3 0 ; ( 2 2 ) 58 Afza, N. ( 8 ) 2 ; ( 9 ) 3 Agrawal, S . ( 2 0 ) 136 Agzamkhodzhaeva, D.R. (18) 10 Ahmad, S. ( 7 ) 7 Ahmad, Z. ( 9 ) 9 , 16 A i c h e r , T.D. ( 2 4 ) 69 Ajisaka, K. ( 3 ) 59 A k a h o s h i , A. ( 2 3 ) 28 A k a i , S . ( 3 ) 25

A k a s h i , S. (19) 41 A k a t s u k a , H. ( 3 ) 124 A k h t a r , M. ( 1 9 ) 18 Akishina, R . I . ( 2 ) 3 Akiyama, S . ( 3 ) 87 Akram, M. ( 2 ) 65 Akuda, S . S . ( 1 9 ) 2 Alais, J. ( 4 ) 48 A l b o r n , H. ( 2 2 ) 2 2 ; ( 2 3 ) 34 A l b o r n , W.E., j u n . ( 1 9 ) 21 A l b r a c h t , .J.H. ( 2 3 ) 61 A l d e r , L . ( 2 2 ) 14 A l d e r w e i r e l d t , F.C. ( 2 0 ) 7 , 8 6 ; ( 2 2 ) 2 1 ; ( 2 3 ) 78 Alemany, A. ( 1 0 ) 2 0 ; ( 2 1 ) 1 9 , 3 4 , 4 6 ; ( 2 2 ) 3 0 , 56 A l h , R . (16) 2 6 , 27 A l e x o f f , D.L. ( 8 ) 22 A l f o l d i , J. ( 2 ) 2 5 ; (10) 6 A l l a u d e e n , H.S. ( 1 9 ) 69 A l l e n , N.E. ( 1 9 ) 21 A l l e r h a n d , A. ( 2 ) 41 A l l e v i , P. ( 3 ) 129, 130, 160 Al-Masoudi, N.A.L. ( 1 1 ) 2 0 , 21 A l o n s o , D. ( 2 4 ) 19 Alonso-Lopez, M. ( 5 ) 1 9 ; ( 1 8 ) 25 h a t , E. ( 2 ) 61 Ambrose, M.G. ( 8 ) 4 5 ; ( 1 3 ) 12 Aminev, I . H . ( 2 2 ) 8 Anand, K.K. ( 3 ) 34 A n a s t a s i a , M. ( 3 ) 1 2 9 , 1 3 0 , 160 Anazawa, K. ( 7 ) 9; ( 1 6 ) 4 8 ; ( 2 2 ) 68 A n d e r l e , D. ( 7 ) 6

Andersen, J. ( 9 ) 26; (20) 8 A n d e r s o n , J . D . ( 2 0 ) 124 A n d e r s o n , M. ( 5 ) 24 A n d e r s o n , P.C. ( 3 ) 116 Ando, T. ( 1 9 ) 41, 7 8 A n d r e a s s e n , E.S. ( 9 ) 2 5 , 27; ( 2 0 ) 8 A n g e l o t t i , T. ( 1 6 ) 4 ; ( 2 1 ) 17 Angermann, A. ( 2 4 ) 63 A n g y a l , S.J. ( 5 ) 45 A n i s u z z a m a n , A.K.M. (9) 21 A n k e r , D. (8) 13; ( 9 ) 5 5 ; ( 2 3 ) 90 A n k e r , G . ( 9 ) 5 5 ; ( 2 3 ) 90 A n k n e r , K. ( 1 3 ) 37; ( 2 4 ) 99 Anraku, Y. ( 2 3 ) 32 A n s a r i , A.A. ( 3 ) 48 A n t o n a k i s , K. ( 3 ) 1 4 6 ; (5) 21 A n t o n o p o u l o s , C.A. ( 2 3 ) 30

A o k i , H. ( 1 9 ) 72 A o k i , Y. ( 1 8 ) 85 Aoyama, H. ( 2 0 ) 4 0 , 41 A p a r i c i o , F.J.L. ( 3 ) 1 1 9 ; (11) 4 A p e l l , H.-J. ( 3 ) 68 A p p a r a o , S. ( 3 ) 123; ( 1 6 ) 29 A q e e l , A. ( 9 ) 33; ( 1 4 ) 9 A q u i l a n o , D. ( 2 2 ) 25 Arai, I. ( 1 8 ) 68 Arai, Y. ( 1 9 ) 61 Araki, Y. ( 3 ) 1 5 5 , 161 Arbuzov, B.A. ( 7 ) 55; ( 1 7 ) 15 Arcamone, F. (19) 32 A r e v a l o A r e v a l o , M. A.

275

Author index (20) 9 1 Argay, G. ( 2 2 ) 41, 42 A r g o u d e l i s , A.D. ( 1 9 ) 4 4 , 76, 77 Ariono, D. ( 2 ) 4 Arita, M. ( 1 9 ) 6 5 Armistead, D.M. ( 3 ) 8 4 ; (24) 5 , 54 A r n e t t , G. (20) 9 3 , 101 Arnold, R. ( 1 6 ) 6 3 ; ( 2 2 ) 98 Arora, K.K. ( 7 ) 56 Asano, H. ( 5 ) 13 A s c h e r l , B. (10) 42 Asenjo, R. ( 1 0 ) 9 Asheervadam, Y. ( 1 4 ) 18 Ashwell, M. (20) 3 2 , 80 A s p i n a l l , G.O. ( 4 ) 24; (8) 43; (13) 36 Atal, C.K. ( 3 ) 34 Atashyan, S.M. ( 2 ) 51; ( 2 2 ) 102 Atopkina, L.N. ( 3 ) 38, 39 A t t a g h r a i , J. ( 9 ) 55; (23) 90 Auchus, R.J. ( 7 ) 6 3 Aug6, C. ( 1 6 ) 4 0 A u r e l l e , H. ( 2 2 ) 11 A u s t i n , G.N. ( 5 ) 4 1 ; ( 1 8 ) 38; ( 2 4 ) 80 Autenrieth-Ansorge, L. ( 1 4 ) 31; ( 1 8 ) 27; (22) 64 Auzannaeu, F.-I. ( 1 6 ) 34 Avalos G o n z a l e z , M. ( 9 ) 5 , 71; (10) 22 Avramenko, V.G. (10) 4 Azerad, R . ( 1 6 ) 31 Azhaev, A.V. (20) 6 6 Azuma, I. ( 7 ) 4 7 ; ( 1 8 ) 24 Baba, M. ( 2 0 ) 53, 6 0 Baba, Y. ( 7 ) 51 Babiano C a b a l l e r o , R. ( 9 ) 6 Babichev, F.S. (3) 30 B a b i r a d , S.A. (3) 159; (21) 4 8 Back, D.M. (22) 4 Backinowsky, L.V. ( 4 ) 3 2 Baczko, K. ( 7 ) 13 Baczynskyj, L. ( 1 9 ) 4 4 , 76, 77 Badone, D. ( 8 ) 11 B a e n z i g e r , J . U . ( 4 ) 15 B a e r , H.H. (10) 5 4 ; (18) 68 B a g g e t t , N. (14) 5; ( 1 8 ) 29 B a i , D.-L. ( 3 ) 113; ( 1 3 ) 15; ( 2 4 ) 50, 53

B a i r d , P.D. ( 1 8 ) 3 8 ; ( 2 2 ) 52; ( 2 4 ) 76, 80 B a j p a i , C.D. ( 2 ) 57 B a j p a i , P.S. ( 2 ) 55 Baker, D.C. (18) 6 4 ; ( 1 9 ) 60 Baker, D . J . (18) 103 Baker, R . ( 1 8 ) 101, 102; ( 2 2 ) 76 B a k i n o v s k i i , L.V. ( 3 ) 105; ( 7 ) 76 Bakd, P. ( 9 ) 8 Bakthavachalarn, V. ( 6 ) 1 2 ; ( 2 0 ) 141, 146 B a l g o b i n , N . (20) 1 2 3 B a l i n o v , Ya. ( 6 ) 5 B a l l a b i o , M. (19) 32 B a l l o u , C.E. ( 2 2 ) 10 Balsa, F. ( 1 8 ) 59; ( 2 3 ) 87 B a l z a r i n i , J. (19) 55; (20) 53, 6 0 Ban, C. ( 9 ) 42 Ban, Y. ( 2 4 ) 3 4 , 4 8 Banaszek, A. ( 4 ) 9 ; ( 2 2 ) 41, 42 Bandouzi, A. ( 3 ) 170; (24) 64 B a n e r j e e , A . (22) 8 2 B a n f i , L. ( 9 ) 37 Bankova, W. (18) 8; ( 2 4 ) 96 Banoub, J. ( 9 ) 52 B a p t i s t a , J. ( 5 ) 1 6 Bar, T. ( 3 ) 6 8 Baranowska, E. ( 1 3 ) 8; (14) 30 Barba, F. ( 1 5 ) 1 2 Barbalat-Rey, F. ( 1 0 ) 47 B a r b a t , J. ( 5 ) 1 9 ; ( 6 ) 7, B a r b i e r i , B. (19) 32 B a r i , S.S. ( 9 ) 35 B a r i l i , P.L. (12) 26 Barrera, J.B. ( 1 4 ) 4 Barrett, A.G.M. (10) 5 ; (16) 17 Barrio, J . R . ( 8 ) 31 Bartra, M. ( 9 ) 72; ( 1 0 ) 35 Barua, A.B. ( 3 ) 49 B a s h y a l , B.P. (18) 3 5 , 3 9 , 4 0 ; ( 2 4 ) 77-79 B a s s e l l , G. (23) 58 B a t e l a a n , J . G . ( 5 ) 37 B a t l e y , M. (5) 44; (16) 33 B a t t a , G. (11) 11; (13) 27 Bauer, T. (12) 18; (13) 20; (18) 5 4 ; ( 2 4 ) 9 8 B a u t e , M.-A. ( 5 ) 30; (22) 58

B a u t e , R. ( 5 ) 30; (22) 58 Bax, A. ( 2 1 ) 5 2 B a z i n , H. (20) 5 4 , 78, 79 R e a t t y , N.B. ( 2 3 ) 4 3 Beau, J.M. ( 3 ) 125; ( 6 ) 15; ( 1 6 ) 19 Beaugage, S.L. (20) 129 Becker, D.P. ( 2 4 ) 10 Begley, M . J . ( 2 2 ) 77 Behrens, G. ( 2 ) 49 Beigel'man, L.N. ( 1 4 ) 10; ( 2 0 ) 74, 75; ( 2 2 ) 83 B e k e l e , T.S. ( 1 7 ) 22 B e l a n g e r , K. (23) 75 B e l l o s t a , V. ( 3 ) 151 Belmans, M. ( 2 0 ) 86; ( 2 2 ) 21; (23) 78 Belter, R.K. ( 1 4 ) 7 ; (16) 6 4 ; ( 2 4 ) 23 B e l z e c k i , C. ( 1 3 ) 7 , 8; (14) 30, 3 2 ; (24) 8 7 , 88 B e M i l l e r , J.N. ( 2 ) 1 9 , 20; ( 2 2 ) 37 Ben Cheikh, A . (19) 6 2 Ben-Hattar, J. (20) 4 5 B e n i g n i , D.A. (20) 5 9 B e n i t e z , F.Z. ( 3 ) 119; (11) 4 Bennek, J . A . ( 3 ) 135 Bentley, R. (2) 9 Benz, G. ( 1 9 ) 4 6 Benzing-Purdie, L.M. (10) 26 Berad, B.N. (10) 1 6 BerAnek, J. ( 2 0 ) 28; ( 2 2 ) 81 Berclaz, T. ( 2 2 ) 101 Beres, J. ( 2 0 ) 9 4 B e r g e r , M. ( 2 0 ) 56 Bergman, A. ( 7 ) 8 2 Bergogne, M.-C. (20) 23, 24; (23) 6 4 , 6 5 Bergstroem, K. (23) 1 Bergstrom, D. (20) 6 3 Berki, R.J. (7) 66 Bernabe, M. (10) 20; (21) 1 9 , 27, 34; ( 2 2 ) 29, 30, 56 B e r n a c k i , R . J . (20) 120 Bernadou, J. (20) 152 B e r n a t o s , R.C. ( 1 8 ) 4 1 , 42 B e r n s t e i n , S. ( 7 ) 81 B e r t h a u l t , P. (21) 39 Berti, G. ( 1 2 ) 26 B e r t u c c i , C. (18) 26; (22) 106 B e t a n e l i , V . I . (6) 1 4 B e t z , R. ( 3 ) 153 Beurskens, P.T. (22) 35 Bhargava, A.K. (20) 39

Carbohydrate Chemistry

276 Bhargava, V.O. (23) 47 Bhatia, S.C. (20) 153, 154

Bida, G.T. (8) 31 Bieber, L.W. (19) 31 Biggadike, K. (20) 95-97; (22) 97

Bigorra, J. (24) 17 Bilik, V. (2) 25 Billiet, H.A.H. (7) 72 Billington, D.C. (18) 101, 102; (22) 76

Binder, H. (23) 26 Bindig, U. (20) 46, 49 Binkley, R.W. (7) 66; (8) 45; (12) 17; (13) 12

Biondi, L. (7) 34 Biondi, P.A. (23) 12 Birberg, W. (4) 47 Bird, P. (3) 31; (8) 19 Birnbaum, G.I. (21) 35; (22) 66, 81, 88

Biswas, G. (22) 82 Bizzozero, N. (10) 47 Blackburn, G.M. (20) 119 Blake, J . D . (23) 48 Blake, T.J. (3) 122 Blattner, R. (3) 157; (16) 68; (18) 72

Blau, P.A. (22) 19; (23) 71

Blazej, A. (16) 1 Blazquez, J.A.S. (16) 11 Bliard, C. (8) 3; (19) 27 Blokh, E.L. (18) 11 Blumberg, K. (11) 7 Bobek, M. (20) 42 Bobleter, 0. (23) 26 Bock, K. (3) 57, 69; (9) 19; (12) 3; (24) 21

Bodenteich, M. (20) 98, 99

Boerner, A. (18) 47, 50 Bognar, R. (1) 2; (13) 27 Bogusiak, J. (11) 8 Boivin, T.L.B. (24) 59 Bolte, J. (2) 31 Bonn, G. (23) 27 Bonnert, R.V. (14) 41; (15) 1

Bontemps-Gracz, M. (19) 38

Booth, H. (21) 7 Borchardt, R.T. (16) 24; (19) 63

Borcherding, D.R. (16) 24; (19) 63

Bordoni, T. (19) 32; (20) 10

Borghi, C. (23) 73 Borisenko, A.A. (7) 49 Bormann, C. (19) 45

Bornhop, D.J. (23) 20 Borodkin, V.S. ( 1 4 ) 25; (24) 42-45

Borowski, E. (19) 38, 39 Borthwick, A.D. (20) 95-97;

(22) 97

Boryski, J. (20) 22 Bosch, F. (23) 11 Boshagen, H. (18) 43 Bossennec, V. (21) 39 Botta, M. (18) 4 Bottka, S. (20) 125 Bouhroum, S. (13) 3 Boulanger, P. (9) 52 Bourgeois, W. (20) 48 Bousfield, G.R. (23) 95 Boyd, J. (21) 38 Boyd, R. (22) 80 Brade, H. (4) 22; (5) 5; (7) 54; (22) 15; (23) 2, 3 Brakta, M. (3) 149 Brandstetter, H.H. (16) 46; (21) 37 Brandt, E.V. (3) 82 Brasch, R.C. (21) 26 Brehm, M. (13) 16; (24) 68 Breitinger, M. (19) 20 Brennan, P.J. (4) 24 Brewster, K. (18) 81; (24) 6 Brieden, M. (19) 46 Brill, W.K.-D. (20) 118 Brimacombe, J.S. (2) 34, 35; (18) 2 Briner, K. (17) 2 Brinkmeier, A. (2) 38 Brisson, J.-R. (21) 35; (22) 66 Brockman, R.W. (20) 7 1 Broder, S. (20) 52, 53 Brodfuehrer, P.R. (20) 59 Brokes, J. (3) 95; (9) 59 Broser, E. (14) 2 Brossmer, R. (3) 13; (11) 27; (16) 47; (22) 49 Brown, D.P. (19) 23 Brown, P.R. (23) 67, 68, 80 Brown, R.G. (5) 24 Brown, R . J . (9) 43 Bruijn, J.M. (2) 66 Bruins Slot, H.J. (22) 35 Bruno, M. (18) 55 Bruns, W. (24) 70 Bryukhanova, O.V. (6) 14 Buchanan, J.G. ( 5 ) 1; (11) 9; (24) 74, 75 Buck, H.M. (20) 78; (21) 16, 32; (22) 90 Buddrus, J. (2) 38

Budesinskf, M. (22) 8 1 Buege, J.A. (19) 76 Bueno Martinez, M. (18) 15

Butfering, L. (22) 20; (23) 35

Bugianesi, R.L. (3) 122 Buko, A. (19) 22, 23 Bundle, D.R. (3) 101, 102; (4) 38; (10) 32

Burger, J.F.W. (3) 82 Burke, B.A. (7) 14 Burke, M.B. (19) 69 Burley, S.K. (22) 94 Burtscher, E. (23) 26 Bush, C.A. (4) 44; (21) 56

Buzby, J . H . (13) 31 Byrd, G.D. (10) 23 Cabrera Escribano, F. (18) 70

Cadenas, R.A. (6) 6; (18) 34

Cadet, J. (20) 56; (22) 87

Cai, M. (3) 128 Cai, S. (22) 31 Calahorro, C.V. (16) 11 Calvo-Mateo, A . (9) 77 Cameron, T.S. (6) 8; (22) 60

Campbell, S.A. (3) 169 Carnpos-Valdes, M.T. (3) 22

Canas-Rodriguez, A. (19) 7, 8

Cangiani, S.E. (6) 6 Cano, F.H. (10) 20; (21) 19, 27, 34; (22) 29, 30, 56 Capek, K. (7) 21; (9) 74 Capkova, J. (9) 74 Capon, R . J . (11) 18 Cardani, S. (9) 37 Cardellach, J. (24) 19 Caris, R.C.H.M. (16) 23 Carmen Cruzado, M. (5) 18; (7) 24 Carpenter, R.C. (8) 43 Carpy, A . (5) 30; (22) 58 Carr, S.A. (19) 69 Carraher, C.E. (17) 22 Carruthers, M.H. (20) 118 Carver, J.P. (4) 30; (5) 16; (21) 41 Cassinelli, G. (19) 32 Castilla, I.M. (34) 21 Castro, A.L. (9) 50; (22) 50 Catelani, G. (12) 26

277

Author Index

Caubet, A. (17) 32 Caude, M. (23) 17 Cech, D. (20) 130; (22) 14

Cekovic, 2. (18) 19 Celalyan-Berthier, A. (22) 101

Cerezo, A.S. (21) 13 Cermak, J. (21) 42 Cerny, I. (3) 36 Cert Ventula, A. (9) 49; (18) 15

Cha, B.C. (19) 5 Chakir, S. (23) 50 Chakraborty, T.K. (3) 24; (9) 15; (10) 30; (19) 28; (24) 46 Chan, T.H. (3) 58 Chandan, B.K. (3) 34 Chan Van Tan, (12) 15 Chapleur, Y. (3) 170; (14) 39; (24) 64 Chapman, J.R. (22) 18; (23) 36 Charbonneau, C.F. (23) 89 Charon, D. (5) 5; (7) 54; (16) 34; (22) 15; (23) 2, 3 Charubala, R. (20) 105, 111-114 Chatterjee, S. (19) 26 Chattopadhyaya, J. (20) 54, 55, 78, 79, 123, 143, 144; (21) 16 Chechegoeva, E.V. (17) 16 Cheetham, P.S.J. (2) 46 Chen, G. (16) 57, 58 Chen, M.S. (20) 59, 67 Chen, Y. (9) 54 Cheng, J.C.-Y. (13) 14 Cheng, K. (2) 60 Cheng, T. (3) 128 Cheng, X.-M. (3) 177 Cherian, X.M. (6) 12; (20) 141, 146 Chernov, V.A. (10) 4 Chheda, G.B. (20) 39 Chiara, J.-L. (10) 52 Chinh, N. (18) 68 Chipman, D.M. (21) 14 Chirva, V.Ya. (3) 100; (7) 35 Chittenden, G.J.F. (7) 10; (16) 14, 23; (24) 15 Chiu, A.K.B. (14) 1 Chizov, O.S. (14) 19; (22) 16 Chladek, S. (20) 137 Chmielewski, M. (9) 80; (10) 24, 25; (13) 6-8, 19; (14) 28-30, 32;

(16) 12; (18) 54; (21) 8; (24) 87, 88, 98 Choay, J. (4) 39 Chou, T.C. (2) 63 Chow, H.-F. (18) 39, 40; (24) 77, 78 Christensen, S.B. (19) 69 Christian, R. (3) 86; (4) 22; (16) 46; (21) 37 Christodoulou, C. (20) 136 Christofides, J.C. (21) 20 Chujo, R. (21) 54 Chum, H.L. (5) 47 Chung, S.K. (19) 69 Chvalovsky, V. (21) 42, 44 Cimino, G. (11) 23; (20) 72 Ciufolini, M. (19) 79 Ciunik, 2. (22) 55, 6 1 Claesson,'A. (3) 127; (9) 17; (16) 21, 35; (17) 4; (21) 36; (22) 62, 67 Clardy, J. (22) 69 Clarke, M.L. (23) 41, 48 Classon, B. (11) 15 Clayton, S.J. (20) 92 Clinch, K. (24) 85 Coad, P. (16) 65; (22) 12 Coad, R.A. (16) 65; (22) 12 Cockman, M. (2) 39; (3) 112 Cody, V. (22) 86 Coenen, H.H. (8) 28 Colbert, J.C. (2) 36 Coleman, M.T.D. (13) 35; (22) 72 Collins, J.M. (23) 75 Colonna, F. (12) 26 Conant, R. (3) 61; (18) 60-6 2 Concin, R. (23) 26 Conde, A. (22) 57, 96 Conde, C.F. (22) 96 Connor, A.H. (23) 7 Cook, P.D. (20) 2 Cooke, A.M. (18) 93-95 Cooke, K.B. (3) 29 Cookson, D. (2) 46 Cooper, M.D. (8) 27 Coronel-Borges, L.A. (19) 7, 8 Cottam, H.B. (20) 20, 21; (22) a4 Cowart, M.D. (3) 171 Coxon, €3. (2) 36; (10) 23; (12) 2; (21) 9 Crain, P.F. (20) 39, 127 Cremata Alvarez, J. (2)

42

Crispino, A. (11) 23; (20) 72

Cristalli, G. (20) 10 Cristescu, C. (20) 4 Crout, D.H.G. (16) 28 Csoregh, I. (21) 36; (22) 67

Csuk, R. (16) 54 Cuberta, A. (20) 25 Cumming, D.A. (21) 41 Curran, D.P. (3) 148; (24) 67

Cusmano, J. (14) 51 Czarnik, A.W. (6) 12; (20) 141, 146

Czernecki, S. (3) 151 Czerwinski, A. (19) 38 Dabrowski, J. (21) 57 D'Accorso, N.B. (10) 45, 46; (21) 10-12

Dachmann, J. (14) 31; (22) 64

Dahlhoff, W.V. (3) 9; (17) 18, 19, 20

Daines, R.A. (3) 24; (9) 15; (10) 30; (19) 28; (24) 46 Dais, P. (2) 4_' Dakenova, N.S. (9) 47, 48 Dalgaard, L. (7) 23 Dalley, N.K. (3) 131; (10) 43; (20) 5, 57; (22) 85 Daniel, J.R. (11) 25; (18) 52 Danilov, L.L. (7) 48, 50 Danishefsky, S.J. (1) 1; (2) 32; (3) 84, 145; (8) 38; (13) 17; (14) 27; (19) 79; (22) 48; (24) 5 , 54, 55 Darlow, S.F. (22) 27 Da Silva Filho, A.A. (19) 31 Date, T. (8) 4 1 Date, V. (3) 166; (18) 5 Datta, S.P. (20) 39 Dauben, W.G. (13) 16; (24) 68 Daves, G.D. (3) 172; (13) 14 David, S. (5) 9 Davidson, R.M. (10) 23 Davies, D.B. (21) 20 Dawe, R.D. (3) 141 Dax, K. (8) 17; (13) 10 Debongnie, P. (17) 31 de Bruijn, J.M. (2) 10; (16) 25

Carbohydrate Chemistry

2 18 d e Bruyn, R.G.M. (16) 23 DeClercq, E. ( 1 9 ) 55; (20) 23, 24, 32, 42, 4 3 , 53, 6 0 , 130 D e c l e r c q , G. ( 2 ) 4 Defaye, J. ( 1 0 ) 6 D e f f i e u x , G. (5) 30; ( 2 2 ) 58 de F i n a , G.M. (13) 15 Defoin, A. ( 9 ) 8 2 de Galan, L. ( 7 ) 72 Dehbi, A. ( 2 ) 13; ( 1 1 ) 2 De Hey, H.T. ( 9 ) 13 D e i s e n r o t h , T.W. ( 9 ) 75 D e j e s u s , O.T. ( 8 ) 27 D e Las Heras, F.G. (5) 39; (9) 77; (10) 44; (18) 18; ( 1 9 ) 50 Delatre, S. ( 3 ) 146 D e l b a e r e , L.T.J. ( 2 2 ) 8 9 d e Lederkremer, R.M. ( 1 2 ) 14; (13) 15 d e L e e r , E.W.B. ( 7 ) 72 De Lima, O.G. ( 1 9 ) 31 Dell, A. ( 2 2 ) 10 D e l r i e u , P. ( 2 3 ) 59 De MCllo, J . F . ( 1 9 ) 31 De Miguel, I. ( 2 3 ) 60 Demuynck, C. ( 2 ) 31 Den D r i j v e r , L. ( 6 ) 4 ; ( 1 5 ) 1 1 ; ( 2 2 ) 65 DeNimo, S. ( 3 ) 145 DeNinno, M.P. ( 2 ) 3 2 ; ( 8 ) 38; ( 2 2 ) 4 8 Denisenko, V.A. ( 3 ) 39 Denmark, S.E. ( 5 ) 20 Depezay, J.-C. ( 1 8 ) 13; ( 2 4 ) 86, 9 5 D e p h i l l i p s , P.A. (19) 6 9 , 70 d e Raadt, A. ( 3 ) 4 D e r e v i t s k a y a , V.A. ( 1 0 ) 2 Derome, A.E. ( 3 ) 9 3 DeRudder, J. (20) 23, 24 D e s c o t e s , G. ( 8 ) 18, 35; ( 9 ) 52; (10) 1 2 ; ( 2 2 ) 44 Deshmukh, S.P. (10) 1 6 DeShong, P. (17) 1 0 deSolms, S . J . (18) 9 6 , 9 8 E e s s i n g e s , A. ( 8 ) 5 DeStefano, S. ( 1 1 ) 23; (20) 72 Deulofeu, V. (10) 10; (21) 15 Dev, S. (18) 6; ( 2 4 ) 89 Devadas, B. (10) 57; (16) 20 De Vries, N.K. ( 2 1 ) 3 2 De W i t , D. ( 9 ) 13 d e W i t , M.S. (23) 61 Dezwaan, J. (19) 77

Dhanak, D. ( 1 6 ) 1 7 Dhar, T.G.M. (24) 9 1 Dho, J . C . ( 2 2 ) 52; ( 2 4 ) 76 DiAnez, M . J . ( 9 ) 50; ( 1 8 ) 51; ( 2 2 ) 50, 51, 7 3 , 74 Diaz, J. (14) 4 d i B e l l o , I . C . (24) 81 D i e t r i c h , W. (9) 8 D i k s i c , M. ( 8 ) 23 D i n g e r d i s s e n , J.J. ( 1 9 ) 6 9 , 70 Dipaolo, M. ( 1 9 ) 6 9 Do, J.S. ( 2 ) 6 3 Doboszewski, B. (3) 52; (8) 14 Dodgson, S.P. ( 7 ) 70 Dolphin, D.H. (3) 3 1 ; ( 8 ) 19 Domalski, E.S. ( 2 ) 36 Dommisse, R. ( 2 0 ) 7 Do Nascimento, M.S. ( 1 9 ) 31 Dondoni, A. ( 1 5 ) 1 6 Doner, L.W. (23) 18 Dong, L. ( 3 ) 128; ( 2 0 ) 18 Dornhagen, J. ( 7 ) 26; (19) 84 Doutheau, A. ( 3 ) 11; ( 1 6 ) 30 Dovichi, N . J . (23) 20 Drasar, P. ( 3 ) 36; (20) 28 Dreux, M. ( 2 3 ) 21 Driller, H. ( 2 0 ) 46, 49 D r i s c o l l , J.S. ( 2 0 ) 5 2 , 100 Du, J. ( 5 ) 23 Dubey, R. ( 3 ) 72, 73; ( 4 ) 20; (15) 9 , 10 Duchaussoy, P. ( 4 ) 39 D u c k s t e i n , V. ( 3 ) 83 Duda, A. (14) 31; (22) 64 Duddeck, H. (10) 1 9 ; (19) 82 Dudycz, L.W. (20) 50 Dufat-Trinh Van, H. ( 1 9 ) 37 Duhamel, P. ( 7 ) 6 9 Dunkerton, L.V. ( 3 ) 150 Dupin, P. (23) 59 Dupuis, J. ( 3 ) 156; ( 2 2 ) 63, 9 9 D u r e a u l t , A. (18) 13; (24) 86, 95 Dwek, R.A. (21) 38, 58 Dyatkina, N.B. ( 2 0 ) 6 6 Dzhorupbekova, D. ( 7 ) 6 1 Dzhumanazarova, A.Z. ( 2 ) 5 D z i e d z i c , S.Z. (14) 1 Dziewiszek, K. (4) 9

E a t o n , M.A.W. ( 2 2 ) 38 E b a t a , M. (9) 1; (19) 74 Eddine, J.J. ( 7 ) 6 9 Edgar, A.R. ( 1 1 ) 9 ; (24) 74 Edrnonds, C.G. (20) 127 Edmonds, J . S . (17) 6 , 7 E f e n b e r g e r , G. ( 3 ) 133, 134 E f f e n b e r g e r , F. ( 7 ) 5 2 E g e r t , E. (10) 4 8 E j c h a r t , A. ( 2 1 ) 5 7 Ekstrom, B. ( 9 ) 1 7 Elango, V. (17) 10 E l Ashry, E.S.H. (3) 40; (6) 1; (10) 49, 51, 56; ( 1 6 ) 69 E l i e , C . J . J . ( 9 ) 76 Eliseeva, G.I. (7) 61 E l Khadem, H.S. ( 2 ) 21 E l K i l a n y , Y. (3) 4 0 ; ( 1 0 ) 51 E l k i n k i , Y.N. (22) 8 E l l e n b e r g e r , S.R. (9) 4 6 ; ( 1 4 ) 15 E l l i o t t , R.D. (20) 3 4 , 71 Endo, T. ( 3 ) 155 E n g b e r t s , J.B.F.N. (2) 48 E n g l i s h , R.B. (13) 35; (22) 72 E n n i f a r , S. ( 2 ) 21 E r i t j a , R . (18) 23 E r k e l e n s , C. ( 7 ) 72 Ermolenko, M.S. ( 1 4 ) 25; ( 2 4 ) 42-45 Ermolinsky, B.S. ( 2 0 ) 75; (22) 83 Ershova, Yu.A. ( 1 0 ) 4 E s a k i , S. ( 3 ) 4 4 , 80, 81 E s c h e n f e l d e r , V. ( 3 ) 13 E s c r i b a n o , F.C. ( 8 ) 3, 5; ( 1 9 ) 27 Esmans, E.L. (20) 7 , 86; (22) 21; ( 2 3 ) 78 E s n a u l t , J. ( 6 ) 15; (16) 19 E s s a d i q , H. (20) 135 E s t r a d a , M.D. ( 2 2 ) 57 Etoh, Y. ( 1 9 ) 4 1 Euske, J . M . ( 3 ) 150 E u v r a r d , M.-N. (14) 39 Evans, D. (20) 95 Evans, R.P. ( 8 ) 6 Evans, W . J . (18) 105 Evtushenko, E.V. (5) 2 E x a l l , A.M. ( 2 0 ) 95-97; (22) 97 E z u r e , Y. (22) 53 F a b e r , K. (20) 98 F a d n i s , A.G. ( 2 ) 5 4

Author Index F a g h i h , R. (14) 43, 47, 51 Falkowski, L. ( 1 9 ) 39 Falshaw, C.P. ( 2 2 ) 77 Fang, Y. ( 5 ) 33 F a n t i n , G. ( 1 5 ) 16 Fanton, E. ( 5 ) 1 9 ; ( 6 ) 7 F a r a z d e l , A. ( 1 1 ) 1 9 F a r k a s , I. ( 1 1 ) 11; ( 1 8 ) 48; (22) 45 F a r k a s , J. ( 3 ) 95; ( 9 ) 5 9 F e d a r , L.R. (3) 120 Fedoronko, M. ( 2 ) 14 F e h l h a b e r , H.-W. ( 7 ) 32; ( 1 3 ) 18; ( 1 9 ) 26, 8 2 F e i , C.P. ( 3 ) 58 F e i b u s h , B. (23) 79 F e l b e r , H. ( 1 0 ) 42 F e l c z u k , K. (20) 1 F e l d b e r g , R.S. ( 2 3 ) 1 6 F e l l o w s , L.E. (18) 37, 39; ( 2 4 ) 77 Femia, R.A. (23) 2 3 F e n i c h e l , L. ( 9 ) 8 Fennessey, P.V. ( 4 ) 44 Fermandjian, S. ( 2 1 ) 33 Fernandes, A.A. ( 1 0 ) 53 Fernandez, J.M.G. ( 9 ) 70 Fernandez-Bolanos, J. (9) 5, 49; ( 1 0 ) 21; ( 1 1 ) 26 Fernandez-Bolanos Guzman, J. ( 1 1 ) 26 Fernandez C i r e l l i , A. (12) 14 Fernandez-Mayoralas, A. ( 5 ) 9 , 19; ( 6 ) 7 ; ( 2 1 ) 46 Fernandez Molina, L. ( 2 ) 42 F e r r e i r a , D. (3) 8 2 F e r r i e r , R . J . ( 3 ) 4 , 157; (16) 68; ( 1 8 ) 72 F e r r i s , J.P. (10) 5 7 ; (16) 20 F e r r o , D.R. (16) 52 F i a n d o r , J. ( 1 9 ) 50 F i e c c h i , A. (3) 129, 130, 160 Figueiredo, J.A. (14) 4 F i l i p p i , J. (5) 21 F i l i r a , F. ( 7 ) 3 4 F i n d e i s , M.A. (12) 24 F i r g a n g , S . I . ( 7 ) 77 F i s c h e r , R. (3) 5, 6 , 42 Fishman, R.M. (23) 5 6 Fitzsimmons, B.J. (9) 21; (13) 5; (24) 60 F l e e t , G.W.J. (3) 167; (5) 41; (8) 1 2 ; ( 9 ) 1 4 ; (10)’ 31; (18) 35-40; (22) 52; (24) 7 6 - 8 0 Flippen-Anderson, J.L.

279 ( 2 2 ) 40 F l o r e n t , J.-C. ( 5 ) 6 ; ( 7 ) 5 ; ( 9 ) 29; (24) 71 Foces-Foces, C. (10) 20; ( 2 1 ) 1 9 , 27, 34; ( 2 2 ) 29, 30, 5 6 Fodor, G. (16) 6 3 ; (22) 98 F o e r t s c h , A. ( 3 ) 132 Fogagnolo, M. ( 1 5 ) 16 Fonseca, B. ( 1 0 ) 21 F o n t , J. ( 2 4 ) 17-19 Ford, K.G. ( 2 2 ) 38 F o r t s c h , A. ( 1 0 ) 39 F o t h , H. (23) 83 Fowler, J.S. ( 8 ) 22 Fox, J.J. ( 2 0 ) 6 1 F r a n c h e t t i , P. ( 2 0 ) 10 Franco, C.M.M. (19) 26 Franke, W. (24) 70 Franken, G.A.M. (16) 1 4 ; ( 2 4 ) 15 F r a n t s i , M. (24) 99 Franzkowiak, M. ( 7 ) 60 Fraser-Reid, B. ( 3 ) 141, 166; ( 1 4 ) 4 0 , 44-48, 51; ( 1 8 ) 5 , 30; ( 2 4 ) 47 Frechou, C. ( 1 8 ) 1 Freeman, F. (3) 168 F r e e s e , S. ( 2 0 ) 50 F r e j d , T. (3) 48; ( 2 4 ) 7 , 65 F r e l e k , J. ( 1 7 ) 23; (22) 108 F r i c k , W. (3) 123; (16) 29 F r i t z , H. ( 9 ) 8 2 F r i t z , J.S. ( 2 3 ) 88 Fronza, G. (12) 25 F r o u s s i o s , C. ( 1 6 ) 31 F r u s h , H.L. ( 3 ) 111 Fuchs, P.L. (3) 126; (17) 12 F u g e d i , P. ( 3 ) 79; ( 4 ) 4 7 F u e n t e s Mota, J. ( 9 ) 49, 7 0 , 71; ( 1 0 ) 21 F u g a n t i , C. (12) 2 5 F u g i t a , K. ( 1 8 ) 9 F u j i i , A. (19) 53 F u j i i , M. (20) 131; (23) 92 Fujirnori, H. (23) 8 2 Fujimoto, H. ( 3 ) 59; (14) 6 F u j i s h i m a , Y. ( 7 ) 38-41, 47; (9) 65, 6 6 , 68, 69; (11) 5; ( 1 8 ) 24 F u j i t a , K. (24) 97 F u j i t a , M. (3) 88; ( 7 ) 38, 40, 41; (9) 65, 66, 69 F u j i t a , S. (3) 20

F u j i w a r a , T. ( 4 ) 24, 25 Fukabori, C. ( 1 8 ) 7 3 , 74 Fukagawa, Y. ( 1 9 ) 24, 25 Fukami, H. ( 2 4 ) 62 Fukarni, N . ( 2 4 ) 8 F u k a t s u , S. ( 1 9 ) 6 Fuke, A . ( 2 3 ) 8 2 Fukuda, H. ( 8 ) 25; (13) 9 Fukukawa, K. ( 2 0 ) 108 Funabashi, M. ( 5 ) 3 2 ; (10) 55 F u r i h a t a , K. ( 1 9 ) 29, 30, 43 Furo, I. ( 2 1 ) 5 5 F u r u h a t a , K. ( 3 ) 20; ( 7 ) 9 ; ( 1 6 ) 48; ( 2 2 ) 6 8 F u r u i c h i , K. (24) 4 Furukawa, H. ( 3 ) 173, 174; (20) 8 9 F u s e t a n i , N. ( 3 ) 109 Fushimi, F. (16) 66 Gabe, E.J. ( 2 2 ) 88 G a d l e r , H. (20) 8 7 G a e t j e n s , E. ( 2 0 ) 58 Gagnet, R . ( 5 ) 6 ; ( 7 ) 5 G a i n o r , J . A . ( 9 ) 4 4 , 45 Gait, M . J . ( 2 0 ) 136 Gajdus, J. ( 1 8 ) 16 Gakhokidze, R.A. ( 2 ) 11; ( 1 2 ) 15; ( 1 6 ) 7 , 8 Galan, E.R. ( 1 6 ) 11 GalAn, J. ( 1 8 ) 51; ( 2 2 ) 73 G a l b i s P e r e z , J . A . (9) 5 , 6 ; (10) 18, 22; (18) 15; ( 2 0 ) 9 1 Galdyan, A.A. ( 3 ) 33 G a l i c i o , M. ( 6 ) 6 Gamian, A. ( 3 ) 1 4 ; ( 1 6 ) 44 Ganem, B. (18) 4 1 , 42; (24) 8 2 G a n g u l i , B.N. (19) 26 Ganguly, A.K. ( 1 9 ) 85; (22) 9 Gao, F. ( 2 2 ) 3 4 Gao, Y.-S. (20) 6 7 Garaeva, L.D. (20) 1 7 Garcia, A.B. (16) 11 Garcia, J. ( 1 0 ) 27 Garcia, P.A. (15) 1 2 Garcia-L6pez, M.-T. ( 5 ) 39; ( 1 0 ) 44; (18) 18; (19) 50 Garcia-Martin, M.G. ( 3 ) 23; ( 9 ) 50, 51; ( 2 2 ) 50 Garcia-Ochoa, S. (13) 22, 24, 32; ( 1 6 ) 13; (17) 13 Garcia-Raso, A . ( 2 ) 4 3 ;

Carbohydrate Chemistry

280

(23) 9 Garcia-Raso, J. (23) 9 Garcia Segura, R. (13) 38 Gardocki, J.F. (7) 70 Garegg, P.J. (4) 47; (11) 15; (20) 126 Gasch, C. (3) 23; (9) 50, 51; (22) 50 Gass, J. (3) 86 Gatley, S.J. (8) 27 Gautheron, C. (16) 40 Gavagnin, M. (11) 23; (20) 72 Gavin, N. (7) 65 Gelas, J. (2) 13; (5) 19; (6) 7; (11) 2 Gelpi, M.E. (6) 6; (18) 34 Genestar, C. (2) 61 Geoffroy, M. (22) 101 George, C. (16) 63; (22) 98 Gerasimov, P.A. (18) 11 Gerber, G. (23) 76 Gering, B. (15) 3 Gerken, M. (3) 101; (4) 26; (10) 32; (14) 3 Geroni, C. (20) 10 Gesson, J.-P. (19) 36; (24) 28, 29 Ghazzouli, I. (20) 59, 67 Gherezhiher, T. (23) 44 Ghosh, M. (9) 35 Giannis, A. (3) 142 Giannousis, P.P. (22) 47 Giese, B. (3) 156; (12) 11; (14) 23, 24; (22) 63, 99 Giese, R. (23) 79 Gigg, J. (3) 61; (18) 60-62 Gigg, R. (3) 61; (18) 60-62, 91-95 Gilardi, R. (22) 40 Gilbert, B.E. (23) 74 Gilron, I. (10) 54 Giovenella, A.J. (19) 69, 70 Girgis, N.S. (20) 20, 21; (22) 84 Giuliano, R.M. (9) 75; (13) 31 Giziewicz, J. (20) 1; (22) 88 Glanzer, B.I. (8) 17; (13) 10; (16) 54 Glaudemans, C.P.J. (3) 6 3 ; (4) 3; (8) 20; (21) 29 Glodek, J. (13) 34 Gluzinski, P. (22) 41, 42 Gnichtel, H. (14) 31;

(22) 64 Gobbo, M. (7) 34 Goda, S.K. (19) 18 Godefroi, E.F. (16) 14, 23; (24) 15 Goekjian, P.G. (3) 158; (21) 28, 47, 48 Goerlach, A. (3) 5 Golankiewicz, B. (20) 22 Goldsby, G. (7) 14 Golebiowski, A. (9) 80, 81 Golic, L. (22) 36 Golubovskaya, L.E. (8) 40 G6mez-SBnchez, A. (3) 23; (9) 50, 51; (10) 52; (18) 51, 70; (22) 50, 73 Gomi, S. (19) 3 Gonzalez, A.G. (14) 4 Gonzalez, F.S. (3) 119; (11) 4 Gonzalez, L. (3) 62 Goodman, M.F. (18) 23 Goren, M.B. (7) 18 Gorshkova, R.P. (14) 17 Gosselin, G. (20) 23, 24; (23) 52, 64, 65 Goto, A. (23) 82 Goto, M. (16) 48; (22) 23, 68; (23) 39 Goto, T. (3) 16, 18, 19, 113, 144; (4) 14; (13) 15; (14) 53; (16) 41-43; (24) 8, 9, 50-53 Gottlieb, H.E. (2) 12; (7) 2 Gough, M.J. (18) 35; (24) 79 GOUX, W.J. (21) 40 Goya, P. (20) 14, 15, 26 Gramatica, P. (3) 140 Grand, A. (22) 87 Grappel, S.F. (19) 70 Grases, F. (2) 61 Grasselli, P. (12) 25 Graves, D.D. (12) 19 Gravier, C. (18) 13 Gray, G.R. (3) 135 Grebner, K.D. (19) 23 Greck, C. (18) 13; (24) 86 Green, M. (20) 148 Grein, A. (19) 32 Gretz, M.R. (23) 25 Griengl, H. (20) 43, 98, 99, 133 Gries, P. (9) 56 Griest, W.H. (23) 91 Grifantini, M. (20) 10 Grim, R. (22) 14 Grindley, T.B. (5) 24;

(6) 3, 8; (22) 60 Grishakov, A.N. (2) 3 Groninger, K.S. (12) 11; (14) 23; (22) 99 Gromadzinska, E. (7) 78; (18) 20 Grotjahn, L. (7) 16 Grouiller, A. (20) 135 Gruber, L. (20) 94 Gubareva, A.I. (18) 11 Guder, H.-J. (3) 5, 6 Guerra, F.I. (20) 109 Guffreda, P. ( 3 ) 129, 130, 160 Guga, P. (20) 115, 116 Guindon, Y. (3) 116 Gupta, R. (20) 127 Gurarii, L.I. (7) 55 Gurjar, M.K. (5) 8, 43; (9) 12, 18; (13) 21; (15) 13; (24) 27, 91, 94 Gurskaya, G.V. (20) 75; (22) 83 Gyorgydeak , Z. (8) 44; (10) 29 Ha, D.-C. (9) 36 Haag-Zeino, B. (3) 123; (16) 29 Haasnoot, C.A.G. (22) 35 Habermas, K.L. (5) 20 Hadfield, J.A. (16) 28 Hadzik, P. (16) 55 Hafele, B. (16) 15; (18) 3; (24) 14, 92, 93 Hagedorn, H.N. (22) 49 Hahn, C.S. (13) 23 Hahn, H. (19) 45 HajdukoviC, G. (16) 55 Hakimelahi, G.H. (20) 138 Hale, K.J. (3) 77, 78; (10) 36; (19) 81 Hall, J.H., jun. ( 2 0 ) 153, 154 Halmos, T. (5) 21 Hamacher, K. (8) 28 Hamada, M. (19) 3, 25 Hamada, T. (14) 49, 50; (24) 35-40 Hamana, H. (24) 82 Hamazaki, H. (23) 31 Hamblin, M.R. (18) 91, 92 Hammer, R.P. (5) 20 Hammond, S.M. (9) 17 Han, 0. (12) 13 Hanaki, A. (18) 46 Hanaya, T. (17) 1 Handa, S. (14) 40 Haneda, T. (3) 124; (20) 102, 103

Author Index Haneishi, T. ( 1 9 ) 68 Hanessian, S . ( 1 8 ) 4 ; ( 2 4 ) 16

Hanfland, P. ( 2 1 ) 57 Hanna, N.B. ( 1 9 ) 5 6 ; ( 2 0 ) 51

Hanna, R. ( 1 8 ) 2 Hansen, A. ( 2 ) 28 Hansen, S.H. ( 7 ) 23 Hansen-Moller, J. ( 7 ) 23 Hansske, F. ( 1 9 ) 55 Hanus, V. ( 1 6 ) 2 Hanvey, J.C. ( 1 9 ) 60 Happ, E. ( 2 0 ) 137 Haque, M.E. ( 6 ) 1 1 ; ( 7 ) 7 4 ; ( 1 1 ) 1 7 ; ( 1 2 ) 9 , 10

Hara, K. ( 1 4 ) 6 Hara, 0. ( 3 ) 173, 174; (20) 89

Hara, S. ( 2 3 ) 8 Harada, K. ( 2 0 ) 61 Haradahira, T. ( 8 ) 21 Harangi, J. ( 4 ) 4 1 ; ( 2 4 ) 66

Haremsa, S. ( 3 ) 8 Haromy, T.P. ( 2 2 ) 37 Harrison, J.M. ( 1 8 ) 8 1 ; (24) 6 Hart, D.J. ( 9 ) 36 Harvey, D.F. ( 1 3 ) 1 7 ; ( 1 4 ) 27

Hasegawa, A. ( 3 ) 1 5 , 8 8 , 9 0 ; ( 7 ) 38-41, 4 7 ; ( 9 ) 65-69; ( 1 1 ) 5 , 1 4 , 2 4 ; ( 1 8 ) 24 Hasegawa, S. ( 1 9 ) 53 Hashimoto, H. ( 3 ) 3 2 ; ( 8 ) 41; (13) 13; (14) 6 , 9 , 35, 36; ( 2 4 ) 4 Hashimoto, K. ( 3 ) 109 Hashimoto, M. ( 1 8 ) 4 6 ; ( 1 9 ) 72 Hashimoto, S. ( 1 4 ) 14 Hashizume, T. ( 2 0 ) 127 Haslam, E. ( 2 2 ) 77 Hassel, T. ( 1 0 ) 17 Hata, T. ( 2 0 ) 128, 131 Hatano, T. ( 7 ) 27-29; ( 1 9 ) 83 Hauser, F.M. ( 9 ) 4 6 ; ( 1 4 ) 15 Havel, M. ( 3 ) 36 Hay, G.W. ( 8 ) 14 Hayakawa, H. ( 2 0 ) 76 Hayakawa, Y. ( 1 9 ) 2 9 , 3 0 , 4 3 , 7 5 ; ( 2 0 ) 107 Hayashi, E. ( 3 ) 88 Hayashi, M. ( 2 0 ) 1 2 Hayashi, S. ( 5 ) 1 1 Hayashi, Y. ( 1 9 ) 61 Hayashida, M. ( 1 9 ) 1 4 Heald, S.L. ( 1 9 ) 6 9 , 71

28 1 Hegde, V.R. ( 9 ) 35 Hehemann, D.G. ( 8 ) 4 5 ; ( 1 3 ) 12

Heidar, A. ( 2 ) 67 Heiker, F.R. ( 1 8 ) 43 Heins, H. ( 1 4 ) 2 Heitsch, H. ( 1 9 ) 45 Helm, R.F. ( 2 3 ) 7 Helpap, B. ( 3 ) 60 Hendry, D. ( 1 0 ) 3 8 ; ( 2 4 ) 5 7 , 8 3 , 84

Hennen, W.J. ( 3 ) 1 3 1 ; ( 1 0 ) 4 3 ; ( 2 0 ) 9 , 120 Hentzschel, A. ( 2 4 ) 63 Her, G.R. ( 2 2 ) 7 , 2 4 ; ( 2 3 ) 29, 38 Herak, J.H. ( 2 ) 49 Herczegh, P. ( 1 3 ) 27 Herderling, W. ( 2 0 ) 49 Herdewijn, P. ( 2 0 ) 5 3 , 60 Hermann, K. ( 7 ) 16 Hermans, J.P.G. ( 9 ) 76 Hernandez, A. ( 1 8 ) 2 5 ; ( 2 4 ) 32 Herradh, B. ( 5 ) 2 2 ; ( 1 3 ) 3 2 ; ( 2 4 ) 3 2 , 33 Herscovici, J. ( 3 ) 146 Herz, W. ( 1 8 ) 55 Herzig, J. ( 2 ) 1 2 ; ( 7 ) 2 Hewitt, B.D. ( 2 4 ) 7 4 Hicks, K.B. ( 2 3 ) 1 8 , 19 Hidai, M. ( 2 ) 2 2 , 2 4 ; ( 2 2 ) 70 Hidalgo, F.-J. ( 1 0 ) 52 Higuchi, H. ( 1 5 ) 1 5 ; ( 2 1 ) 24 Higuchi, T. ( 2 2 ) 53 Hikichi, K. ( 2 1 ) 50 Hikino, H. ( 4 ) 45 Hikota, M. ( 2 4 ) 41 Hildebrand, C. ( 2 0 ) 50 Hiler, G.D., jun. ( 3 ) 56 Hiltmann, A. ( 1 9 ) 82 Himmelsbach, F. ( 2 0 ) 1 0 5 , 112 Hindsgaul, 0. ( 3 ) 6 6 , 7 1 ; ( 4 ) 6 , 7 , 15; ( 7 ) 58, 62 Hindsgaul, V. ( 4 ) 15 Hines, J.W. ( 2 2 ) 1 9 ; ( 2 3 ) 71 Hintsche, R. ( 1 2 ) 1 Hirai, K. ( 2 3 ) 82 Hiram, M. ( 9 ) 38 Hirayama, K. ( 1 9 ) 4 1 , 78 Hirono, S . ( 1 7 ) 22 Hirota, K. ( 2 0 ) 3 0 , 3 3 , 35 Hirota, T. ( 4 ) 45 Hirotsu, K. ( 2 2 ) 53 Hirsch, J. ( 2 1 ) 42-44 Hiyama, T. ( 9 ) 39

Hizukuri, S. ( 2 3 ) 40 Ho, C.-T. ( 9 ) 7 Hoagland, P.D. ( 1 6 ) 67 Hochlowski, J.E. ( 1 9 ) 22 Hofer, 0 . ( 2 4 ) 100 Hoffman, N.E. ( 2 3 ) 7 0 Hoffmann, R.W. ( 1 2 ) 20 Hofmeister, G.E. ( 2 2 ) 47 Hohnjec, M. ( 2 0 ) 88 Holy, A. ( 2 0 ) 122, 130 Holzapfel, C.W. ( 6 ) 4 ; (13) 1 ; (15) 11; (22) 65 Homans, S.W. ( 2 1 ) 3 8 , 58 Honda, S . ( 1 8 ) 3 3 ; ( 2 3 ) 84 Honda, T. ( 3 ) 1 3 8 ; ( 9 ) 42; ( 1 0 ) 8 Honeyman, T.W. ( 2 3 ) 58 Honig, H. ( 1 1 ) 22 Hoogerhout, P. ( 4 ) 33 Hoppe, D. ( 1 4 ) 38 Hori, H. ( 5 ) 4 6 ; ( 9 ) 2 2 ; ( 1 5 ) 15; ( 2 1 ) 24; ( 2 4 ) 26 Horii, H. ( 1 6 ) 56 Horino, I. ( 1 9 ) 41 Horita, K. ( 1 4 ) 4 9 ; ( 2 4 ) 3 5 , 58 Horito, S. ( 8 ) 41

Hormaza Montenegro, J. ( 2 ) 42

Horton, D. ( 5 ) 1 9 ; (6) 7 ; ( 9 ) 21; ( 1 0 ) 50; ( 2 1 ) 8

HorvAth, Cs. ( 2 3 ) 66 Hoshijima, Y. ( 8 ) 3 4 ; (15) 7

Hoshikawa, S. ( 2 ) 24 Hoshino, M. ( 1 8 ) 7 6 , 8 7 , 89

Hoshino, Y. ( 1 9 ) 65 Hosomi, A. ( 3 ) 136 Hosseini, M.W. ( 2 0 ) 150 Hotta, K. ( 2 3 ) 31 Hotta, Y. ( 1 8 ) 7 3 ; ( 2 4 ) 81

Hough, L. ( 1 0 ) 3 6 , 3 8 ; ( 1 4 ) 1 ; ( 2 4 ) 5 7 , 8 3 , 84

Howard, R.R. ( 2 3 ) 51 Howell, H.G. ( 2 0 ) 59 Howie, R.A. ( 2 2 ) 9 1 Hruska, F.E. ( 2 2 ) 87 Hu, L. ( 6 ) 2 Huang, J.-X. ( 2 3 ) 66 Iiuang, Q. ( 2 2 ) 31 Huang, T.C. ( 9 ) 7 Huber, R. ( 1 0 ) 40 Huckerby, T.N. ( 1 6 ) 53 Huff, J.R. ( 1 8 ) 9 6 , 98 Hughes, N.A. ( 1 1 ) 2 0 , 21 Hull, W.E. ( 8 ) 24 Hungate, R. ( 2 4 ) 54

Carbohydrate Chemistry

28 2 Hunter, S.W. ( 4 ) 24 Hutchison, D.K. ( 3 ) 1 2 6 ; ( 1 7 ) 12

Hutchison, R.J. (11) 9 Hutt, J. ( 1 2 ) 2 2 ; ( 1 8 ) 1 Huynh-Dinh, T. ( 2 0 ) 109 Hvidt, T. ( 9 ) 30 Hwang, B.J. ( 2 ) 63 Hwang, C.J. ( 2 3 ) 92 Ichikawa, S. ( 2 ) 2 6 ; ( 1 5 ) 14

Ichikawa, Y. ( 3 ) 1 1 3 , 144, 1 6 3 ; ( 1 3 ) 1 5 ; ( 1 4 ) 53; ( 1 9 ) 5 1 , 52; ( 2 4 ) 50-53 Ichimura, M. ( 1 9 ) 73 Ido, T. ( 2 ) 1 6 ; ( 8 ) 2 5 , 26; ( 1 3 ) 9 Idogaki, Y. ( 1 4 ) 26 Ignatov, L . A . ( 2 0 ) 31 Iguchi, H. ( 1 9 ) 25 Ii, Y. ( 3 ) 107; ( 1 5 ) 4 Iida, H. ( 9 ) 41; ( 1 8 ) 3 1 , 44 Iida, T. ( 1 8 ) 82 Iijima, T. ( 3 ) 174 Iijima, Y. ( 1 9 ) 4 7 , 48 Iimura, Y. ( 1 8 ) 7 6 , 7 7 , 86 Iinuma, H. ( 1 9 ) 58 Iitaka, Y. ( 2 0 ) 76 Ikbal, M. ( 1 8 ) 88 Ikeda, K. ( 3 ) 9 6 ; ( 5 ) 1 5 ; ( 7 ) 43-46; ( 9 ) 60-63 Ikeda, T. ( 1 6 ) 6 6 ; ( 1 9 ) 3 Ikekawa, T. ( 5 ) 10 Ikenaka, T. ( 4 ) 3 7 ; ( 9 ) 34 Ikota, N. ( 1 8 ) 4 6 ; ( 2 4 ) 82 Ikramutdinova, M.T. ( 1 8 ) 10 Ikura, M. ( 2 1 ) 50 Imai, K. ( 2 0 ) 140 Imai, T. ( 4 ) 5 Imamura, K. ( 1 9 ) 43 Imamura, N. ( 1 9 ) 59 Imamura, S . ( 2 0 ) 108 Imanaka, H. ( 1 9 ) 72 Imanari, T. ( 2 3 ) 28 Imbach, J.-L. ( 2 0 ) 2 3 , 2 4 ; ( 2 3 ) 6 4 , 65 Imoto, M. ( 3 ) 1 2 , 9 7 , 9 8 ; ( 1 6 ) 3 2 ; ( 2 2 ) 46 Ina, K. ( 1 8 ) 56 Inaue, Y. ( 5 ) 3 Inazu, T. ( 3 ) 2 Inch, T.D. ( 1 8 ) 8 1 ; ( 2 4 )

6 Inchauspe, G. ( 2 3 ) 59

Inners, R.R. ( 3 ) 169 Inokawa, S . ( 1 7 ) 1 Inomata, K. ( 2 4 ) 12 Inoue, K. ( 1 8 ) 9 ; ( 2 4 ) 97 Inoue, M. ( 1 0 ) 8 Inoue, N. ( 2 3 ) 42 Inoue, Y. ( 2 1 ) 54 Iqbal, J. ( 7 ) 7 Iribarren, A . M . ( 1 6 ) 49 Irie, H. ( 2 4 ) 62 Irinoda, K. ( 5 ) 10 Irvine, R.F. ( 1 8 ) 103 Isaka, H. ( 1 0 ) 3 ; ( 2 2 ) 54 Isakova, V.V. ( 1 4 ) 17 Isbell, H.S. ( 2 ) 2 1 ; ( 3 ) 111

Ishida, H. ( 7 ) 4 0 , 4 7 ; ( 9 ) 6 5 ; ( 1 8 ) 24

Izawa, A . Izquierdo 10 Izumi, K. Izumi, S.

( 2 3 ) 32

Cubero, I. ( 6 ) ( 2 1 ) 25 ( 4 ) 25

Jablonowski, M. ( 2 ) 38 Jacobsen, J.P. ( 9 ) 2 5 , 2 7 ; ( 1 3 ) 8 ; ( 1 4 ) 30

Jacobsson, U. (9) 8 0 , 81 Jacquesy, J.-C. ( 2 4 ) 2 8 , 29

Jacquinet, J. ( 3 ) 8 5 ; ( 4 ) 3 9 ; ( 7 ) 79

Jager, K.F. ( 1 4 ) 23 Jager, V. ( 1 6 ) 1 5 ; ( 1 8 ) 3 ; ( 2 4 ) 1 4 , 8 2 , 93

Ishida, K. ( 2 2 ) 70 Ishida, N . ( 1 4 ) 42 Ishido, Y. ( 3 ) 155, 1 6 1 ;

Jafri, J. ( 1 7 ) 29 Jain, R.K. ( 3 ) 7 2 , 7 3 ;

( 8 ) 3 6 ; ( 9 ) 2 4 ; (11) 12, 13: (12) 5 ; (13) 2 5 , 2 6 ; ( 2 0 ) 1 1 0 , 134 Ishii, D. ( 2 2 ) 2 3 ; ( 2 3 ) 39 Ishii, I. ( 2 3 ) 31 Ishii, M. ( 2 3 ) 82 Ishikura, T. ( 1 9 ) 2 4 , 25 Ishiwata, K. ( 2 ) 1 6 ; ( 8 ) 26 Ismael, I. ( 1 4 ) 4 Isobe, M. ( 3 ) 113, 1 4 4 ; (13) 15; (14) 53; (24) 8 , 9 , 50-53 Isogai, A. ( 1 8 ) 8 4 ; ( 1 9 ) 2 Isshiki, K. ( 1 9 ) 58 Isumi, K. ( 9 ) 73 Ito, H. ( 7 ) 1 1 Ito, S . ( 9 ) 38 Ito, Y. ( 3 ) 1 7 , 7 0 , 7 4 ; ( 4 ) 11, 40; (12) 12; ( 1 9 ) 1; ( 2 2 ) 2 3 ; ( 2 3 ) 39 Itoh, F. ( 9 ) 40 Itoh, H. ( 1 9 ) 5 4 ; ( 2 0 ) 77 Itoh, M. ( 3 ) 2 0 ; (7) 9 ; ( 8 ) 25; ( 1 3 ) 9 Itoh, N. ( 2 0 ) 76 Itoh, S. ( 1 6 ) 6 Itoh, T. ( 3 ) 147 Itoh, Y. (11) 1 4 Ivanov, I. ( 6 ) 5 Ivanova, N.V. ( 2 2 ) 3 Ivin, P.C. ( 2 3 ) 41 Iwai, Y. ( 5 ) 11 Iwakiri, T. ( 1 9 ) 4 3 Iwamori, M. ( 2 3 ) 32 Iwase, H. ( 2 3 ) 31 Iwata, R. ( 8 ) 26 Iyobe, A. ( 5 ) 3 8 ; ( 1 9 ) 57

Jain, S.M. ( 3 ) 34 Jajicek, J. ( 3 ) 9 5 ; ( 9 )

( 7 ) 5 7 ; ( 1 5 ) 9 , 10 59

Janairo, G. ( 1 0 ) 33 Janssen, A.M. ( 1 6 ) 2 1 ; ( 9 ) 17; (17) 4

Jansson, P.-E. ( 2 1 ) 22 Jarosz, S . ( 2 ) 3 3 ; ( 1 3 ) 34

Jarrahpour, A . A . ( 2 0 ) 138 Jarret, R.M. ( 2 1 ) 1 3 Jary, J. ( 9 ) 7 4 Jasinka, J. ( 2 2 ) 61 Jaurand, G. ( 6 ) 1 5 ; ( 1 6 ) 19

Jeanloz, R.W. ( 4 ) 34 Jeffrey, G.A. ( 2 2 ) 3 2 , 7 5 , 95

Jeffs, P.W. ( 1 9 ) 6 9 , 71 Jenkins, I.D. ( 7 ) 18, 59 Jenkins, P.R. ( 1 4 ) 4 1 ; (15) 1

Jenner, M.R.

( 5 ) 25; ( 8 )

3 2 ; ( 9 ) 11

Jennings, H.J. ( 3 ) 1 4 , 6 4 , 118; ( 4 ) 1 3 ; ( 9 ) 2 ; ( 1 6 ) 44; ( 2 1 ) 35; ( 2 2 ) 66 Jerkovics, G. ( 1 5 ) 17 Jeroncic, L.O. ( 1 2 ) 1 4 Jezek, J. ( 3 ) 9 5 ; ( 9 ) 59 Jiang, C. ( 1 8 ) 6 4 Jiang, T. ( 2 ) 18 Jigajinni, V.B. ( 2 4 ) 75 Jimenez, M. ( 2 3 ) 1 1 Jimenez-Barbero, J. ( 1 0 ) 20; ( 2 1 ) 1 9 , 27, 3 4 ; ( 2 2 ) 2 9 , 3 0 , 56

Jimenez Requejo, J.L. (9) 5 .. 7 1 .: (.1 0.) 22 ( 2 0 ) 1 4 , 25,

Jirneno, M.L.

283

Author Index 2 6 ; ( 2 1 ) 46 J i n , T. ( 1 8 ) 21 J i n , W.-Z. ( 1 9 ) 19 J i r i c n y , J. ( 2 0 ) 45 Johnson, C.R. ( 1 9 ) 64 . J o l l y , D. ( 8 ) 23 J o l y , J . P . ( 2 3 ) 53 Jommi, G. ( 8 ) 11 J o n e s , A.S. ( 2 0 ) 32, 80 J o n e s , J.R. ( 2 0 ) 56 J o n e s , P.G. ( 1 4 ) 38 J o r d a n , A.D. ( 2 4 ) 13 J o s e p h , J.P. ( 3 ) 26; ( 7 ) 81 J o s h i , B.V. ( 2 4 ) 27 Jow, J.J. ( 2 ) 63 J o y c e , R.P. ( 9 ) 4 4 , 45 J u e t t e r i , P. ( 1 9 ) 84 J u l i n a , R. ( 1 6 ) 39 Jung, G.L. ( 5 ) 3 5 ; ( 8 ) 4 J u n g , K.S. ( 1 3 ) 23 J u n i o r , P. ( 1 5 ) 3 J u r c z a k , J. ( 9 ) 8 0 , 8 1 ; (10) 24; (12) 18; (13) 6 , 8 , 19, 20, 37; ( 1 4 ) 28, 3 0 ; ( 1 6 ) 1 2 ; ( 1 8 ) 5 4 ; ( 2 1 ) 8 ; ( 2 4 ) 98 J u t t e n , P. ( 7 ) 26

Kabat, M.M. ( 2 0 ) 85 K a b i r , A.K.M.S. ( 2 ) 34, 35; (18) 2 Kadentsev, V . I . ( 1 4 ) 19; ( 2 2 ) 16 Kadoya, S . ( 7 ) 17 Kaeppi, R . ( 2 0 ) 145 Kageyama, S . ( 8 ) 15 Kahl, G.F. ( 2 3 ) 83 Kaike, K. ( 3 ) 46 K a i s e r , K. ( 2 0 ) 49 Kaiser, S.L. ( 7 ) 63 Kakehi, K. ( 1 8 ) 3 3 ; ( 2 3 ) 84 Kakimoto, K. ( 1 1 ) 16 Kakusawa, N. ( 1 4 ) 4 9 ; ( 2 4 ) 35 Kaliannan, P. ( 2 ) 6 K a l l i n , E. ( 1 8 ) 32 Kalman, A . (11) 1 1 ; ( 2 2 ) 41, 4 2 , 45 Kalman, M. ( 1 6 ) 9 Kaluza, Z. ( 1 0 ) 25; ( 1 3 ) 7 , 8 ; (14) 29, 30; (24) 88 Kalycheva, I.S. ( 3 ) 33 Kamaike, K. ( 2 0 ) 110, 134 Kameda, Y. ( 1 8 ) 77 Kamerling, J.P. ( 7 ) 8 Kametani, T. ( 3 ) 138; ( 9 ) 42 Kameyama, K. ( 2 0 ) 3 0 , 33

Kamiya, S. ( 3 ) 44, 8 0 , 81 Karniyama, K. ( 9 ) 7 9 ; ( 1 8 ) 65 Kanada, K. ( 9 ) 42 Kanai, K . ( 9 ) 7 8 ; ( 1 9 ) 9-13 K a n a t z i d i s , M.G. ( 2 0 ) 149 Kanazawa, Y. ( 8 ) 21 K a n d l i k a r , S . ( 2 ) 56 Kaneda, T. ( 7 ) 27 Kaneko, C. ( 3 ) 124; ( 2 0 ) 102, 103 Kaneko, M. ( 1 9 ) 4 7 , 48 Kanemitsu, K. ( 6 ) 1 1 ; ( 7 ) 74; (11) 16, 17; (12) 9 , 10 Rang, H.-Y. ( 2 1 ) 47 Kanie, 0. ( 1 1 ) 1 4 , 24 Kanou, K. ( 3 ) 41 K a n t e r s , J . A . ( 2 2 ) 90 Kantoci, D. ( 3 ) 9 3 ; ( 9 ) 58 Kanzaki, T. ( 2 3 ) 31 Kaplan, B.E. ( 1 8 ) 23 Karamanos, N.K. ( 2 3 ) 30 Kargacin, M.E. ( 2 3 ) 58 Karger, B. ( 2 3 ) 79 Kariko, K. ( 2 0 ) 114 Karimov, S.T. ( 1 8 ) 10 Karle, I. ( 1 6 ) 6 3 ; ( 2 2 ) 98 Karpeisky, M.Ya. ( 1 4 ) 10; (17) 3 ; (20) 74, 75; ( 2 2 ) 83 Kasai, M. ( 2 3 ) 57 Kasai, R . ( 2 3 ) 33 K a s h u t i n a , E.A. ( 2 0 ) 17 Kasper, D.L. ( 4 ) 1 3 ; ( 9 ) 2 Kastl, R.R. ( 2 3 ) 51 K a t a g i r i , N. ( 3 ) 124; ( 2 0 ) 102, 103 Kato, K. ( 1 9 ) 5 1 , 52 Kato, M. ( 1 0 ) 8 Kato, Y. ( 2 3 ) 31 Katoh, T. ( 2 ) 68 K a t o r i , T. ( 5 ) 10 Katrukha, G.S. ( 1 9 ) 67 Katz, L. ( 1 9 ) 23 Kavai, I. ( 2 0 ) 42 Kawa, M. ( 8 ) 41 Kawaguchi, S . ( 2 ) 68 Kawai, H. ( 1 9 ) 30, 40 Kawai, T. ( 1 4 ) 5 3 ; ( 2 4 ) 52 Kawamoto, H. ( 1 7 ) 1 Kawamura, K. ( 3 ) 138 Kawana, M. ( 2 0 ) 6 9 , 82 Kawasaki, T. ( 7 ) 36 Kawauchi, N. ( 1 3 ) 1 3 ; ( 1 4 ) 35, 36 K a y a k i r i , H. ( 1 8 ) 46

Kazimierczuk, Z. ( 2 0 ) 50 Kazmi, N.U.H. ( 9 ) 9 , 16 K e g l e v i c , D. ( 3 ) 9 3 ; ( 9 ) 58 Kehne, A. ( 2 0 ) 49 Keinan, E. ( 2 ) 1 2 ; ( 7 ) 2 Kemps, L. ( 2 0 ) 7 Kenne, L. ( 2 ) 1; ( 2 1 ) 2 2 , 36; ( 2 2 ) 67 Kerber, A. ( 1 1 ) 6 ; ( 1 8 ) 48 Kerekgyarto, J. ( 4 ) 41 Kessler, H. ( 3 ) 45 Khan, A.Q. ( 9 ) 9 , 16 Khan, M.M.T. ( 1 6 ) 60 Khan, M.Y. ( 5 ) 28; ( 2 1 ) 18 Khan, R. ( 5 ) 25, 4 2 ; ( 8 ) 32; ( 9 ) 11; ( 1 3 ) 2 8 ; ( 1 4 ) 37 Khandekar, G. ( 2 4 ) 56 Khare, A . ( 2 2 ) 13 Khare, M.P. ( 2 2 ) 13 Khedhair, K.A. ( 2 1 ) 7 K h i l y a , V.P. ( 3 ) 30 Khondo, L. ( 8 ) 4 3 ; ( 1 3 ) 36 K h o r l i n , A.Ya. ( 3 ) 100; ( 7 ) 35 Khripach, N.B. ( 2 0 ) 111 K i b a y a s h i , C. ( 9 ) 41; ( 1 8 ) 31, 44 Kida, T. ( 1 9 ) 78 Kieboom, A.P.G. ( 2 ) 10, 6 6 ; ( 7 ) 7 3 ; ( 1 6 ) 3 , 10, 25; ( 1 7 ) 1 7 , 30 K i e n l e , M.G. ( 2 3 ) 73 Kigawa, K. ( 7 ) 47; ( 1 8 ) 24 K i h l b e r g , J. ( 1 2 ) 18 Kikuchi, J. ( 2 3 ) 24 Kikuchi, T. ( 6 ) 1 1 ; ( 7 ) 74; (11) 16, 17; (12) 9 , 10 K i k u i r i , H. ( 2 4 ) 34 K i l a n y , Y.E. ( 6 ) 1 ; ( 1 0 ) 49 Killmer, L.B. ( 1 9 ) 69 K i m , C.-H. ( 2 0 ) 6 , 52 K i m , G.R. ( 2 2 ) 14 K i m , H.Y. ( 2 2 ) 1 7 ; ( 2 3 ) 37 K i m , K.S. ( 1 3 ) 23 K i m , Y.-N. ( 2 3 ) 80 K i m , Y.H. ( 2 0 ) 13 Kimura, H. ( 1 8 ) 7 4 , 87 Kimura, M. ( 1 9 ) 4 7 , 48 King-Morris, M . J . (2) 15 K i n i , G.D. ( 3 ) 131; ( 1 0 ) 4 3 ; ( 2 0 ) 9 , 90 K i n o s h i t a , T. ( 1 9 ) 68 Kinzy, W. ( 3 ) 9 4 , 9 9 ; ( 4 )

284 35; (13) 4 K i r i h a r a , M. ( 3 ) 25 K i r k , B.E. ( 2 0 ) 95-97; ( 2 2 ) 97 Kirst, H.A. ( 1 9 ) 21 K i r s t e i n , H. ( 1 8 ) 27 K i s h i , N. ( 7 ) 2 8 ; ( 1 9 ) 83 K i s h i , Y. ( 3 ) 158, 159; ( 2 1 ) 2 8 , 47, 4 8 ; ( 2 4 ) 69 Kiso, M. ( 3 ) 1 5 , 8 8 , 9 0 ; ( 7 ) 38-41, 4 7 ; ( 9 ) 65-69; ( 1 1 ) 5 , 1 4 , 24; ( 1 8 ) 24 Kistay y a, T. ( 2 ) 56 Kita, Y. ( 3 ) 2 5 ; ( 9 ) 40 K i t a d e , Y. ( 2 0 ) 35 Kitagawa, I. ( 1 9 ) 5 Kitagawa, T. ( 2 4 ) 62 K i t a h a t a , S . ( 4 ) 50 Kitayama, I. ( 2 0 ) 40 Kiyoshima, K. ( 1 9 ) 24, 25 Kiyoto, S. ( 1 9 ) 72 Kjaer, A . ( 1 1 ) 28 K l a f f k e , W. ( 1 3 ) 2 9 ; ( 1 4 ) 8 Kleck er, R.W., ju n . ( 2 3 ) 75 K l e i n , U. ( 1 6 ) 1 8 ; ( 1 8 ) 49 Klemer, A. ( 9 ) 23; ( 1 3 ) 2 9 ; ( 1 4 ) 8 , 1 6 ; ( 1 8 ) 83 Klibanov, A.M. ( 7 ) 4 Klimov, E.M. ( 3 ) 5 3 , 5 4 , 75 Klin g , A. ( 3 ) 45 K l i n g l e r , F.D. ( 1 2 ) 2 1 Kloosterman, M. ( 7 ) 3 ; ( 9 ) 13 Knaus, E.E. ( 2 0 ) 62 K n i r e l , Y.A. ( 9 ) 7 4 ; ( 2 2 ) 8 Knodler, U. ( 7 ) 32 Knust, E.J. ( 8 ) 29, 30 Kobata, A. ( 2 3 ) 42 Kobayashi, E. ( 1 9 ) 75 Kobayashi, K. ( 9 ) 3 9 ; ( 2 2 ) 70 Kobayashi, N. ( 3 ) 161 Kobayashi, S . ( 3 ) 162; ( 9 ) 79; (18) 9 , 65; ( 2 1 ) 5 4 ; ( 2 4 ) 97 Kobayashi, Y. ( 1 8 ) 9 ; ( 1 9 ) 6 ; ( 2 4 ) 97 Kobe, J. ( 2 0 ) 88 Koch, M. ( 1 9 ) 37 Kochetkov, N.K. ( 3 ) 50, 5 3 , 5 4 , 7 5 , 105; ( 4 ) 3 2 ; - ( 5 ) 29; ( 6 ) 1 4 ; ( 7 ) 49, 61; (10) 2; (14) 25; ( 2 1 ) 4 5 ; ( 2 4 ) 42-45 Kodama, H. ( 1 9 ) 2

Carbohydrate Chernistry Kodama, T. ( 2 0 ) 40 Kohl er, P. ( 1 3 ) 1 6 ; ( 2 4 ) 68 Kohn, A. ( 1 8 ) 6 6 , 71 Koekemoer, J . M . ( 1 3 ) 1 K o l l , P. ( 3 ) 132; ( 5 ) 4 0 ; (10) 39; (18) 14, 17; ( 2 2 ) 4 3 , 5 9 , 71 Konig, J. ( 2 0 ) 130; ( 2 2 ) 1 Konig, W.A. ( 1 9 ) 38, 45 Kopper, S . ( 5 ) 7 ; ( 1 2 ) 6 ; (13) 2 R o s t e r , R. ( 1 7 ) 18 Kogelberg, H. ( 1 0 ) 39 Kogler, H. ( 1 9 ) 26 Kohata, K. ( 4 ) 28 Kohla, M. ( 1 8 ) 83 Kohne, B. ( 1 8 ) 69 Kohol i c, D . J . ( 7 ) 66 Kohsaka, M. ( 1 9 ) 72 Koike, K. ( 3 ) 9 2 ; ( 4 ) 11 Koizumi, K. ( 2 3 ) 40 Koizumi, T. ( 5 ) 38; ( 1 9 ) 57, 61 Kojic-Prodic, B. ( 2 2 ) 36 Kojima, M. ( 8 ) 21 Kokx, A.J.P.M. ( 1 6 ) 23 Kol ar, C. ( 3 ) 4 5 ; ( 7 ) 32 Kol ar, P. ( 2 ) 58 Kolobushkina, L . I . ( 1 7 ) 3 Kol opzi ej czyk, P. ( 1 9 ) 38 Kolosova, T.E. ( 2 2 ) 3 Komeshima, N. ( 1 9 ) 40 Kondo, H. ( 3 ) 9 6 ; ( 7 ) 4 6 ; ( 9 ) 60 Kondo, S. ( 3 ) 4 3 ; ( 1 9 ) 1 , 3 ; ( 2 4 ) 90 Kondo, T. ( 3 ) 1 6 , 1 8 , 1 9 ; ( 4 ) 1 4 ; ( 1 6 ) 41-43 Kondo, Y. ( 7 ) 6 4 ; ( 1 8 ) 99 Kong, F. ( 5 ) 23, 3 3 , 3 4 ; (7) 25 Konigs, J . J . H . G . ( 1 6 ) 23 Koni shi , I. ( 7 ) 3 9 ; ( 9 ) 68; (11) 5 Konno, M. ( 2 4 ) 3 , 26 Konobe, M. ( 3 ) 144 Konoike, T. ( 3 ) 137 Kooda, S. ( 3 ) 107; ( 1 5 ) 4 Koole, L.H. ( 2 0 ) 7 8 ; ( 2 1 ) 1 6 ; ( 2 2 ) 90 Koomen, G.-J. ( 2 4 ) 73 Kopf, J. ( 1 8 ) 1 4 ; ( 2 2 ) 43, 59, 71 Koppenhoefer, B. ( 1 8 ) 3; ( 2 4 ) 93 Korbukh, I . A . ( 2 0 ) 1.7 Kordowicz, M. ( 2 1 ) 57 Korol i k, E.V. ( 2 2 ) 3 Koroteev, M.P. ( 7 ) 49 Korth, H.-G. ( 1 2 ) 1 1 ;

( 2 2 ) 9 9 , 100 Korytnyk, W. ( 5 ) 3 6 ; ( 8 ) 9 Kosarych, Z. (9) 35 Koseki, K. ( 1 9 ) 2 Koshiura, R. ( 7 ) 28; ( 1 9 ) 83 Kosik, M. ( 5 ) 1 0 ; ( 1 6 ) 1 Kosma, P. ( 3 ) 8 6 ; ( 2 2 ) 15; (23) 2 KOSS, M.C. ( 2 3 ) 44 Koto, S. ( 5 ) 11 Kottenhahn, M. ( 3 ) 45 K O V ~ C , P. ( 4 ) 10; ( 5 ) 3 5 ; ( 8 ) 4 , 20; ( 2 1 ) 29 Kovacs, J. (10) 19 Kowollick, W. ( 1 0 ) 33 Kozaki, S . ( 1 9 ) 49 Kozar, T. ( 2 ) 7 , 8 ; ( 3 ) 117 Kozikowski, A.P. ( 3 ) 137, 175, 177 K oz iolkie w ic z , M. ( 2 0 ) 115 Krach, T. ( 3 ) 5 K r a e v s k i i , A.A. ( 2 0 ) 66 K ra je w s ki, J.W. ( 2 2 ) 4 1 , 42 Krajickovti, J. ( 2 3 ) 45 Kralovec, J. ( 5 ) 24 Kramer, J.B. ( 9 ) 32; ( 1 6 ) 36, 3 7 ; ( 1 7 ) 5 ; ( 2 0 ) 121 Krauze, S . ( 7 ) 7 8 ; ( 1 8 ) 20 Krepinsky, J.J. ( 3 ) 115; ( 4 ) 3 0 ; ( 5 ) 1 6 ; ( 8 ) 42 Kresse, G. ( 1 0 ) 42 Krishnan, L. ( 9 ) 35 Kris ko, M. ( 1 6 ) 4 ; ( 2 1 ) 17 K r i s t e n , H. ( 9 ) 5 6 ; ( 1 8 ) 47, 50 Krohn, K. ( 1 4 ) 2 Kruger, G . J . ( 6 ) 4 ; ( 1 5 ) 1 1 ; ( 2 2 ) 65 Kruggel, F. ( 1 9 ) 82 Krupe ns kii, V.I. ( 2 ) 53 Kubler, D.G. ( 2 ) 3 9 ; ( 3 ) 112 Kubo, K. ( 1 9 ) 24 Kubota, H. ( 3 ) 163 Kubota, Y. ( 2 3 ) 40 Kucar, S . ( 7 ) 6 Kudo, I. ( 1 8 ) 9 ; ( 2 4 ) 97 Kudoh, N . ( 2 3 ) 15 Kufner, U. ( 1 2 ) 23 Kulagowski, J.J. ( 1 8 ) 1 0 2 ; ( 2 2 ) 76 Kulak, T.A. ( 2 0 ) 111 Kulikowski, T. ( 2 0 ) 1 Kumar, A. ( 2 0 ) 32

285

Author Index Kumar, V. (18) 6; (24) 89 Kumari, A. (6) 8; (22) 60 Kumazawa, S. (8) 34; (15) 7 Kunesch, N. (7) 1 Kunisch, F. (19) 82 Kunnen, K.B. (19) 64 Kunz, H. (3) 1, 152; (7) 19; (10) 1, 11 Kuo, L.Y. (20) 149 Kuo, M.T. (19) 44 Kupchevskaya, I.P. (20) 3, 27 Kuroda, R. (22) 93 K u r o t a k i , A. (24) 11, 12 Kur'yanov, V.O. ( 7 ) 35 Kurz, K.G. (3) 114; (5) 14 Kusakabe, I. (2) 17 Kusama, S. (2) 17 Kusayanagi, Y. (20) 40 Kuse, M. (2) 22 Kusuma, S. (6) 8; (22) 60 Kusumoto, S. (3) 12, 97, 98; (7) 37; (16) 32; (22) 46 Kusunose, N. (3) 12; (22) 46 Kuszmann, J. (15) 17 Kuwano, H. (19) 68 Kuzuhara, H. (19) 14; (20) 69, 82 Kvasyuk, E.I. (20) 83, 111 Kvicalova, M. (21) 44

L a b a r t a , A. (17) 32 Laborde, A.L. (19) 44 Labory, P. (23) 50 La Creta, F.P. (23) 72 L a d e s i c , B. ( 7 ) 12 L a f e r r i c k e , C.A. (3) 14; (16) 44 L a f o n t , D. (8) 35; (10) 12 L a f o s s e , M. (23) 21 Lallemand, J.Y. (18) 12 Lam, H.Y.P. (19) 35 Lam, B. (24) 99 Lampilas, M. (18) 12 Lanz, L.W. (12) 20 L a r k i n g , P.W. (23) 4 L a r o c h e l l e , D. (3) 29 L a r s o n , S.B. (20)'20, 21, 51; (22) 84 L a r t e y , P.A. (3) 145; (16) 36; (17) 5; (20) 121 L a s k o l s k i , M. (22) 79 L a t i f , F. (8) 8; (10) 34 L a u r e n t , M. (23) 59

Lavigne, C. (23) 52 Lawrence, J.F. (23) 89 Leblanc, Y. (9) 21; (13) 5; (24) 60 Le Borgne, F. (3) 149 Lebouc, A. (2) 13; (11) 2 Lederman, I. (4) 39 Ledvina, M. (3) 95; (9) 59 Lee, C.K. (5) 26; (7) 68; (8) 33 Lee, E. (7) 65 Lee, Y.C. (8) 10; (9) 53 Lefeuvre, M. (7) 31 L e f r a n c i e r , P. (21) 33 Le Gal-lic, J. (3) 21 Le G o f f , M.Th. (23) 85 Le G o f f i c , F. (18) 88 Lehikoinen, P. (20) 145 Lehmann, J. (3) 7 Lehn, J.-M. (20) 150 L e h r f e l d , J. (23) 5 L e i s i n g , M. (3) 156; (22) 63 Le Marechal, P. (16) 31 Le Merrer, Y. (18) 13 Lemieux, R.U. (21) 5 Lendering, U. (5) 40 L e n h e r r , A. (23) 25 L e p o i v r e , J . A . (20) 7, 86 L e r n e r , L. (20) 58; (21) 52 Leroy, P. (23) 50 Lesimple, P. (3) 125 Lesnikowski, Z.J. (20) 117 L e s s a r d , J. (21) 6 L e v e l , M. (21) 33 Ley, S.V. (18) 57 L i , H. (9) 54 L i , H.-P. (23) 13 L i , R. (7) 15 L i , S.C. (4) 44 L i , S.W. (20) 114 L i , T. (2) 18; (23) 6 L i , W.S. (24) 46 L i , Y.T. (4) 44 Liang, D. (14) 48; (18) 30; (24) 47 L i c h t e n t h a l e r , F.W. (9) 20; (10) 37; (13) 16; (14) 13; (15) 6; (24) 1, 30, 31, 68 L i d a k s , M.J. (20) 83 L i k h o s h e r s t o v , L.M. (10) 2 L i l l e y , T.H. (22) 77 Lim, L.-G. (6) 12 L i n , G.Q. (3) 175 L i n , L.-G. (20) 141, 146 L i n , T.-S. (20) 67; (22) 88

L i n d n e r , H.J. (3) 156; (9) 20; (10) 37; (14) 13; (22) 63 Lindon, J.C. (18) 103 L i n d r o o s , R. (2) 52 L i n d s e t h , H. (5) 25; (8) 32; (9) 11 L i n e k , K. (10) 6 L i o t t a , D. (3) 169 L i p k i n d , G.M. (21) 45 Lippmaa, E. (21) 42, 55 L i p t a k , A. (2) 2; (4) 41; (17) 23; (22) 108 L i s , T. (22) 28 Liskamp, R.M.J. (4) 46 L i t v i n o v , I . A . (7) 55 L i u , B. (2) 44 L i u , C.C. (2) 62 L i u , G. (6) 2 L i u , H.-W. (12) 13 L i u , J. (2) 59 L i u , P.S. (3) 143 L i u , Z. (11) 15 Lloyd-Williams, P. (7) 20 Lonn, H. (18) 32 Lonnberg, H. (16) 9; (20) 143-145 Loganathan, D. (3) 27; (7) 22 London, R.E. (2) 23 Longhi, G. (22) 2 Lonn, H. (3) 51 Lonso-Lopez, M. (6) 7 Lopez-Aparicio, F.J. (3) 176 L6pez-Castr0, A. (18) 51; (22) 51, 73, 74 Lopez Herrera, F.J. (13) 38 Lopez S a s t r e , J . A . (6) 10 Lorentzen, J.P. (3) 60; (4) 21 Lorenz, K. (24) 30, 31 Low, J . N . (22) 80, 9 1 Lubineau, A. (3) 10, 21 Luger, P. (14) 31; (22) 39, 49, 64 Lukacs, G. (8) 3, 5; (19) 27 Lukszo, J. (21) 26 Lundt, I. (9) 19; (13) 2; (24) 21 Luo, S. (3) 106 Luthman, K. (3) 127; (16) 21, 35; (17) 4 ; (21) 36; (22) 62, 67 Luxen, A. (8) 31 Luyten, Y. (22) 21; (23) 78 Ma, W. (15) 6

286 Ma, W.Y. ( 2 4 ) 31 Mabry, T.J. ( 2 2 ) 3 4 ; ( 2 3 ) 25

McAdam, D.P. ( 1 7 ) 8 McAlpine, J.B. ( 1 9 ) 2 2 , 23

McCloskey, J.A. ( 2 0 ) 3 9 , 127

McDonald, G.G. ( 1 6 ) 67 McDowell, C.A. ( 2 1 ) 21 Macek, J. ( 2 3 ) 45 MacGregor, R.R. ( 8 ) 22 Macher, I. ( 7 ) 42 Machulla, H.J. ( 8 ) 2 9 , 30 Maciejewski, S. ( 1 3 ) 1 9 ; ( 1 6 ) 12

McIntire, F.C. ( 4 ) 44 McIntyre, M.K. ( 2 1 ) 1 Mack, H. ( 1 1 ) 2 7 ; ( 1 6 ) 47 McKenna, R. ( 2 2 ) 93 McKernan, P.A. ( 2 0 ) 57 McLaren, C. ( 2 0 ) 67 McLaren, K.L. ( 2 2 ) 47 McLennan, A. ( 2 0 ) 119 MacLeod, J.K. ( 7 ) 5 6 ; ( 1 1 ) 18

McNamara, D.J. ( 2 0 ) 2 McNeil, M. ( 4 ) 44 McNicholas, P.A. ( 5 ) 4 4 ; ( 1 6 ) 33

McPhail, A.T. ( 1 4 ) 40 McPherson, J.D. ( 9 ) 30 Madej, D. ( 1 9 ) 55 Maeba, I. ( 3 ) 173, 1 7 4 ; ( 2 0 ) 89

Maeda, H. ( 1 8 ) 76 Maeda, M. ( 8 ) 21 Maestre Alvarez, A. ( 1 7 ) 25

Magdzinski, L. ( 1 4 ) 4 4 , 45

Maggio, J.E. ( 1 9 ) 82 Magnolato, D. ( 2 2 ) 77 Magnus, P. ( 2 4 ) 1 0 Magnusson, G. ( 3 ) 4 8 ; ( 2 4 ) 7 , 65

Mahato, S.B. ( 2 2 ) 39 Maier-Borst, W. ( 8 ) 24 Majerus, P.W. ( 7 ) 63 Makarova, Z.G. ( 3 ) 5 3 , 5 4 , 75

Maki, Y. ( 2 0 ) 3 0 , 3 3 , 35 Makita, T. ( 1 9 ) 2 Malik, A. ( 8 ) 2 , 8 ; ( 9 ) 3 , 9 , 1 6 ; ( 1 0 ) 34 Malina, H. ( 1 9 ) 66 Malleron, A . ( 3 ) 21 Mal'tsev, S.D. ( 7 ) 50 Maluszynska, H. ( 2 2 ) 95 Malgsheva, N.M. ( 3 ) 5 3 , 5 4 , 75 Mamyan, S.S. ( 2 1 ) 45

Carbohydrate Chemistry Manca, F. ( 2 3 ) 12 Manhas, M.S. ( 9 ) 35 Mani, N.S. ( 1 0 ) 5 Manitto, P. ( 3 ) 140 Mann, B. ( 2 3 ) 1 4 Mann, J. ( 2 2 ) 38 Mansuri, M.N. ( 2 0 ) 59 Mantovani, G. ( 2 2 ) 25 Mao, S. ( 1 8 ) 7 Maple, S.R. ( 2 ) 41 Marat, C. ( 2 1 ) 2 Marchenko, G.N. ( 7 ) 77 Marchettini, N. ( 2 1 ) 49 Mardon, M. ( 2 3 ) 85 Margolis, A. (10) 23 Marino-Albernas, J.R. ( 3 ) 2 2 , 62

Marko-Varga, G. ( 2 3 ) 22 Marks, T.J. ( 2 0 ) 149 Marquardt, P. ( 1 8 ) 69 Mhrquez, R. ( 2 2 ) 5 1 , 5 7 , 7 4 , 96

Marquez, V.A. ( 2 2 ) 86 Marquez, V.E. ( 2 0 ) 6 , 5 2 , 100

Marshall, V.P. ( 1 9 ) 76 Martelli, S. ( 1 9 ) 3 8 , 39 Martin, A . ( 9 ) 1 0 ; ( 1 9 ) 34

Martin, C.J. Martin, J.A. Martin, J.C. Martin, O.R.

( 1 8 ) 105 ( 8 ) 27 ( 2 0 ) 59 ( 3 ) 114,

1 6 4 ; ( 5 ) 14

Martin, R. ( 2 2 ) 77 Martinez, A. ( 2 0 ) 1 4 , 1 5 , 26

Martinez-Castro, I. ( 2 ) 43; (23) 9

Martin-Lomas, M. ( 5 ) 1 8 , 1 9 , 22; ( 6 ) 7 ; ( 7 ) 24; ( 1 0 ) 20; ( 1 3 ) 22, 24, 32; (16) 13; (17) 13; ( 1 8 ) 25; ( 2 1 ) 1 9 , 27, 3 4 , 4 6 ; ( 2 2 ) 29, 3 0 , 5 6 ; ( 2 4 ) 3 2 , 33 Maruoka, K. ( 3 ) 147 Maryanoff, B.E. ( 3 ) 1 6 9 ; ( 7 ) 7 0 ; ( 2 4 ) 13 Masaki, H. ( 1 4 ) 5 3 ; ( 2 4 ) 5 2 , 53 Mash, E . A . ( 6 ) 13 Maskarinec, M.P. ( 2 3 ) 91 Masnovi, J. ( 7 ) 66 Massoud, M.A.M. ( 1 3 ) 33 Mastrorilli, E. ( 1 2 ) 26 Masuzawa, T. ( 3 ) 87 Mateo, 'R. ( 2 3 ) 1 1 Mathlouthi, M. ( 2 2 ) 1 Matsuda, A. ( 1 9 ) 5 4 ; ( 2 0 ) 3 6 3 8 , 7 7 , 108 Matsuda, H. ( 5 ) 10

Matsuda, K. ( 1 9 ) 17 Matsuda, M. ( 7 ) 29 Matsui, T. ( 1 3 ) 1 1 ; ( 1 4 ) 34

Matsumoto, H. ( 2 0 ) 1 3 2 , 142

Matsumoto, K. ( 2 4 ) 62 Matsumoto, S . (19) 2 Matsurnura, G. ( 2 3 ) 15 Matsunaga, S. ( 3 ) 109 Matsuoka, T. (18) 27 Matsuura, T. ( 2 0 ) 147 Matsuura, Y. ( 3 ) 1 2 ; ( 2 2 ) 46

Matsuzawa, S . ( 2 ) 6 8 Matsuzawa, T. ( 8 ) 2 5 ; (13) 9

Matta, K.L.

( 3 ) 67, 72, 7 3 ; ( 4 ) 20, 28; ( 7 ) 57; ( 8 ) 7 ; ( 1 5 ) 9 , 10 Matteson, D.S. ( 2 ) 2 7 ; ( 8 ) 39 Matulewicz, M.C. ( 2 1 ) 1 3 Matulic-Adamic, J. ( 2 0 ) 61 Matulova, M. ( 2 ) 25 Matzke, M. ( 3 ) 83 Maurer, H.W. ( 2 ) 1 9 , 20 Maurer, W. ( 3 ) 8 Maurins, J.A. ( 2 0 ) 8 3 Mawer, I.M. ( 1 8 ) 1 0 2 ; ( 2 2 ) 76 Maya Castilla, I. ( 1 1 ) 26 Mayer, K.K. ( 1 9 ) 20 Mazur, A.W. ( 3 ) 56 M'Boungou, R. ( 2 0 ) 151 Meagher, M.M. ( 2 3 ) 86 Medani, C . ( 5 ) 12 Medich, J.R. ( 1 9 ) 6 4 Medici, A. ( 1 5 ) 16 Meerwald, I. ( 1 8 ) 50 Megges, R. ( 1 2 ) 1 Meguro, H. ( 5 ) 4 6 ; ( 9 ) 22; ( 1 5 ) 1 5 ; ( 2 1 ) 24; ( 2 4 ) 3 , 26 Meier, B. ( 2 3 ) 54 Meijer, E.M. ( 7 ) 3 Melgarejo, M. ( 1 0 ) 9 Mellema, J.R. ( 2 1 ) 31 Mellet, M.C.O. ( 9 ) 70 Mello, R.J. ( 2 3 ) 43 Mellon, F.A. ( 2 2 ) 1 8 ; ( 2 3 ) 36

Mendez-Castrillon, P.P. ( 1 9 ) 50

Merce, R. ( 2 4 ) 18 Mercer, J.R. ( 2 0 ) 62 Mereyala, H.B. ( 3 ) 121 Merienne, C. ( 1 6 ) 34 Merli, S . ( 1 9 ) 32 Merrath, P. ( 1 8 ) 22 Messmer, A . (10) 19

Author index

Mestdagh, M. (17) 31 Metha, R.J. (19) 70 Metternich, R. (12) 20 Metzger, J.O. (18) 14; (22) 71 Meunier, A. (23) 17 Meunier, B. (20) 152 Meyer, B. (21) 53 Micas-Languin, D. (18) 13 Michaelis, H.C. (23) 83 Michalik, M. (18) 47 Michalska, M. ( 7 ) 53; (17) 9 ; (22) 107 Mico, B.A. (19) 69 Mielke, B. (18) 67 Miet, C. ( 7 ) 1 Mihashi, K. (23) 8 Mikami, T. (5) 13 Mikhailopulo, I. A. (20) 83, 111 Mikhailov, S.N. (14) 10; (17) 3; (20) 74, 75; (22) 83; (23) 94 Mikhnovskaya, N.D. (20) 27 Miki, K. (16) 66 Milde, R. (3) 28; ( 7 ) 80 MiljkoviC, D. (16) 55; (24) 66 Millan, M. (22) 96 Miller, D.W. ( 3 ) 37 Miller, J.M. (20) 148 Miller, R. (2) 70 Millican, T.A. (22) 38 MiniC, D. (16) 55 Mirza, M.L. ( 2 ) 65 Misawa, T. ( 5 ) 46 Miskiel, F.J. (2) 44 Mitake, Y. (19) 74 Mitane, M. (18) 58 Mitsunobu, 0. ( 5 ) 1 3 Mitsuya, H. (20) 52 Miwa, T. (24) 4 Miyahara, K. (7) 36 Miyajima, K. (10) 3 ; (22) 54 Miyake, R. (2) 68 Miyaki, Y. (9) 1 Miyamoto, K. ( 7 ) 28; (19) 83 Miyamoto, Y. (19) 15 Miyasaka, T. (20) 76, 81 Miyashiro, S. (19) 78 Miyazaki, M. (18) 74 Miyazawa, K. (18) 82 Miyazawa, T. (20) 128 Mizsak, S.A. (19) 76, 77 Mizuno, T. (22) 23; (23) 39 Mohringer, C. (19) 38 Mohrs, K. (16) 18; (18) 49

287 Mok, D.W.S. ( 3 ) 47 Mok, M.C. ( 3 ) 47 Moliere, P. (20) 135 Molina Molina, J. ( 6 ) 10 Molino, B.F. (14) 44, 45, 51 Molins, E. (17) 32 Moll, H. ( 5 ) 5 ; ( 7 ) 54; (23) 3 Moll, N. (23) 53 Momozono, Y. ( 8 ) 21 Moncelon, F. (23) 85 Mondon, M. (19) 36; (24) 28, 29 Monma, M. ( 2 ) 16 Monneret, C. (5) 6 ; ( 7 ) 5 ; ( 9 ) 10, 29; (19) 34; (24) 71 Monnier, V.M. ( 2 ) 69; (10) 53 Montana, M. (23) 12 Monterrey, I.M.G. (9) 70, 71 Montgomery, J.A. (20) 34, 71, 92 Monti, D. ( 3 ) 140 Montserret, R. (5) 21 Moore, G.L. (23) 56 Mootoo, D.R. (3) 166; (14) 44-46, 51; (18) 5 Moraes de Abreu, C. ( 2 ) 4 Morel, J.-P. (17) 25 Morel-Desrosiers, M. (17) 25 Moreno, V. (17) 32 Morgenlie, S. ( 2 ) 29, 30 Mori, Y. (5) 11 Morii, T. (20) 147 Morikawa, Y. (23) 24 Morin-Allory, L. (23) 21 Morioka, H. (19) 41 Morishima, N. (5) 11 Morissette, D.G. ( 4 ) 38 Morita, M. (17) 6 , 7; (24) 81 Morooka, T. (13) 11; (14) 34 Morris, C.E. (23) 81 Mosmuller, E.W.J. ( 7 ) 3 Mostowicz, D. (13) 8; (14) 30 Motawia, M.S. (9) 25, 27 Mousaad, A . (3) 40; ( 6 ) 1; (10) 51, 56; (16) 69 Moyer, J.D. (18) 64 Mudd, J.B. (7) 14 Muller, B. ( 3 ) 152 Miiller, D . (19) 82 Miiller, E. (22) 39 Miiller, H.P. (10) 17 Mueller, H.W. (16) 60 Mueller, L. (19) 69, 71

Munch, W. (18) 27; (24) 63 Mufti, K.S. (5) 25; ( 8 ) 32; ( 9 ) 11 Mukaiyama, T. ( 3 ) 162 Mukmenev, E.T. ( 7 ) 55; (17) 15 Muller, B. ( 7 ) 19 Muller, I. (16) 39 Mulzer, J. (18) 27; (24) 63 Murai, A. (19) 41, 78 Murai, H. (19) 72 Murakami, K. ( 2 ) 17 Murali Dhar, T.G. (13) 21 Murata, K. (23) 46 Murata, S. (20) 104 Murata, T. ( 2 ) 24 Mure, M. (16) 6 Murofushi, Y. (19) 47 Murray, P.J. (24) 16 Murray, R.D.H. (14) 18 Murufushi, Y. (19) 48 Muyamoto, Y. (19) 9 Myers, R.W. (22) 37 Mykytiuk, P.D. (17) 22 Myles, D.C. (13) 17; (14) 27 Mzengeza, S . (10) 41 Nabiullin, V.N. (17) 15 Nagai, H. (20) 131 Nagai, Y. (23) 32 Naganawa, H. (19) 24, 25, 58 Nagarajan, M. ( 5 ) 31 Nagasawa, J. ( 3 ) 161 Nagasawa, K. ( 5 ) 3 Nagasawa, T. ( 3 ) 155 Nagashima, H. ( 5 ) 32 Nagato, S. (24) 58 Naidoo, N.T. (7) 67; (10) 28 Nair, V. ( 3 ) 26; ( 7 ) 81 Najib, B. (20) 135 Nakabayashi, S. ( 4 ) 34 Nakae, T. (19) 5 Nakagawa, M. (14) 33; (19) 29, 30, 75 Nakagawa, T. (8) 34; (10) 55; (15) 8 Nakahara, H. (10) 3; (22) 54 Nakahara, Y. ( 3 ) 46; ( 4 ) 8, 11, 40, 51 Nakahira, H. (18) 99 Nakajima, M. (19) 68; (20) 76 Nakajima, N. (14) 49; (24) 35, 37, 40 Nakajima, S. (19) 40

Carbohydrate Chemistry

288 Nakamoto, S. ( 3 ) 8 7 , 8 9 ; ( 5 ) 1 5 ; ( 7 ) 43-45; ( 9 ) 61-64 Nakamura, A . ( 3 ) 15 Nakamura, H. ( 2 4 ) 34, 48 Nakamura, J. ( 1 1 ) 1 4 , 24 Nakamura, T. ( 1 9 ) 68 Nakamuwa, K. ( 2 3 ) 24 Nakanishi, H. ( 8 ) 26 Nakanishi, K . ( 5 ) 1 7 ; ( 2 2 ) 109 Nakashima, T. ( 2 4 ) 62 Nakato, 0. ( 2 3 ) 24 Nakayama, J. ( 1 8 ) 84 Nakayama, K. ( 2 0 ) 140 Nakayama, M. ( 3 ) 107; (13) 11; (14) 34; (15) 4 Nambara, T. ( 2 3 ) 49 Naoshima, Y. ( 1 7 ) 22 Narasaka, K. ( 3 ) 163 Narendra, N. ( 2 2 ) 33 Nashed, E.M. ( 3 ) 6 3 ; ( 4 ) 3 Nashimoto, H. ( 9 ) 33 Nasim, F.ul H. ( 2 ) 65 Nasser, M.A. (10) 51 Nawrot, B. ( 2 0 ) 87 Nawwar, G . A . M . ( 9 ) 27 Nedgyes, G. ( 1 5 ) 17 Negri, A . ( 2 3 ) 12 Neidle, S . ( 2 2 ) 3 8 , 93 Nelson, C.R. ( 1 6 ) 5; ( 2 1 ) 30 Nelson, K . A . ( 6 ) 13 Nemal'tsev, V.V. ( 1 4 ) 1 9 ; ( 2 2 ) 16 Nepogod'ev, S . A . ( 3 ) 105; ( 7 ) 76 Neumann, J . M . ( 2 0 ) 109 Neumann, M. ( 3 ) 5 , 6 Neumann, W.P. ( 1 2 ) 8 ; ( 1 4 ) 21 Nickol, R.G. ( 1 0 ) 50 Nicolaou, K.C. ( 3 ) 24; ( 9 ) 1 5 ; ( 1 0 ) 30; ( 1 9 ) 28; ( 2 4 ) 46 Nicolas, A . ( 2 3 ) 50 Nicotra, F. ( 3 ) 3 , 139, 165 Nieduszynski, I.A. ( 1 6 ) 53 Nieger, M. ( 1 0 ) 48 Niemela, K. ( 1 6 ) 6 1 ; ( 2 3 ) 10 Nifant'ev, E.E. ( 7 ) 4 9 ; ( 1 7 ) 16 Nifant'ev, N.E. ( 4 ) 32; ( 2 1 ) 45 Nifontov, V . I . ( 2 ) 3 Niitsuma, S. ( 1 9 ) 51, 52 Nijhof, J. ( 2 3 ) 69

Nikolaev, A . V . ( 3 ) 50 Nilsson, K . G . I . ( 3 ) 65 Nisbet, L . J . ( 1 9 ) 6 9 , 70 Nishi, T. ( 2 4 ) 41 Nishida, H. ( 3 ) 59 Nishida, Y. ( 5 ) 4 6 ; ( 9 ) 22; ( 1 5 ) 1 5 ; ( 2 1 ) 24; ( 2 2 ) 105; ( 2 4 ) 26 Nishide, K . ( 9 ) 39 Nishigaki, J. ( 1 9 ) 1 0 , 11 Nishikawa, T. ( 2 4 ) 8 , 9 Nishikimi, Y. ( 2 4 ) 34 Nishikiori, T. ( 1 9 ) 53 Nishimura, Y. ( 3 ) 4 3 ; ( 2 4 ) 90 Nishino, S. ( 2 0 ) 134 Nishizawa, M. ( 3 ) 103 Niwa, H. ( 3 ) 104 Niwa, T. ( 2 3 ) 49 Nix, M. ( 3 ) 156; ( 2 2 ) 63 Njoroge, F.G. ( 2 ) 6 9 ; ( 1 0 ) 53 Nobori, T. ( 2 0 ) 107 Noda, I. ( 1 4 ) 4 9 ; ( 2 4 ) 35 Noda, N. ( 7 ) 36 Nohle, U. ( 1 6 ) 38 Noguchi, K. ( 2 3 ) 55 Nogueras, M. ( 1 0 ) 9 Nojima, S. ( 1 8 ) 9 ; ( 2 4 ) 97 Nolan, M.C. ( 2 2 ) 47 Nolan, T.G. ( 2 3 ) 20 Nomoto, Y . ( 2 2 ) 104 Nonashita, K. ( 3 ) 147 Norbeck, D.W. ( 9 ) 3 2 ; (16) 36, 37; (17) 5 ; ( 2 0 ) 121 Norberg, T. ( 1 8 ) 32 Nord, L.D. ( 2 0 ) 57 Nordquist, R.E. ( 2 3 ) 44 Nortey, S.O. ( 3 ) 169; ( 7 ) 70 Notermans, S. ( 4 ) 3 3 , 46 Nougier, R. ( 5 ) 12 Novik, E.R. ( 3 ) 110 Novikov, V . L . ( 3 ) 39 Novikova, O.S. ( 1 0 ) 2 Noyori, R. ( 2 0 ) 1 2 , 107 Nozaki, H. ( 3 ) 107; ( 1 5 ) 4 Nudelman, A . ( 2 ) 1 2 ; ( 7 ) 2 Nukada, T. ( 4 ) 40 Numata, M. ( 3 ) 92 Nusselder, J.J.H. ( 2 ) 48 Nyilas, A. ( 2 0 ) 123; ( 2 1 ) 16

Obata, T. ( 1 9 ) 3 Oberdorfer, F. ( 8 ) 24 O'Callaghan, J. ( 7 ) 65

Ochiai, H. ( 2 3 ) 28 Ochoa, C. ( 2 0 ) 15, 25 O'Connor, T. ( 1 6 ) 4 ; ( 2 1 ) 17

Odagawa, A . ( 1 9 ) 40 Odagiri, M. ( 1 8 ) 9 ; ( 2 4 ) 97

O'Dell, C . A . ( 2 0 ) 92, 101 Odier, L. ( 5 ) 45 Oelting, M. ( 1 8 ) 1 4 , 1 7 ; ( 2 2 ) 71

otvos, L. ( 2 0 ) 94 Ogasawara, K. ( 2 4 ) 11, 12 Ogasawara, T. ( 1 8 ) 100 Ogawa, S . ( 9 ) 7 8 ; ( 1 8 ) 80, 8 2 , 85, 8 7 , 89; ( 1 9 ) 9-13, 1 5 , 16 Ogawa, T. ( 3 ) 1 7 , 4 6 , 7 0 , 7 4 , 9 2 ; ( 4 ) 8 , 1 1 , 40, 42, 43, 49, 51; (12) 1 2 Ogawa, Y. ( 3 ) 24; ( 7 ) 38-41, 4 7 ; ( 9 ) 1 5 , 6 5 , 66, 68, 69; (10) 30; (11) 5 ; (18) 24; (19) 28 Ogura, H. ( 3 ) 20; ( 7 ) 9 ; ( 1 6 ) 4 8 ; ( 2 2 ) 68 Oh, A . Y . ( 3 ) 54 Oh, Y.K. ( 1 9 ) 70 Ohashi, S . ( 7 ) 51 Ohba, T. ( 2 0 ) 82 Ohkawa, M. ( 5 ) 10 Ohkawa, T. ( 2 4 ) 12 Ohmori, T. (19) 49 Ohno, M. ( 9 ) 7 9 ; ( 1 8 ) 9 , 6 5 ; ( 1 9 ) 6 5 ; ( 2 4 ) 97 Ohrui, H. ( 5 ) 4 6 ; ( 9 ) 22; ( 1 5 ) 1 5 ; ( 2 1 ) 24; ( 2 4 ) 3 , 26 Ohshiro, Y. ( 1 6 ) 6 Oikarinen, E. (2) 52 Oikawa, Y . ( 1 4 ) 4 9 , 5 0 ; ( 2 4 ) 35-41, 58 Oivanen, M . ( 2 0 ) 143-145 Ojika, M. ( 3 ) 104 Ojima, N. ( 2 2 ) 53 Ojrzanowski, J. ( 1 8 ) 20 Ok, K. ( 8 ) 1 6 ; ( 1 9 ) 33 Okabe, H. ( 2 3 ) 8 Okabe, M. ( 7 ) 36 Okada, S. ( 4 ) 5 0 ; ( 1 0 ) 3 ; ( 1 6 ) 5 6 ; ( 2 2 ) 54 Okada, T. ( 7 ) 71 Okamoto, K. ( 3 ) 1 6 , 1 8 , 1 9 ; ( 4 ) 1 4 ; ( 1 6 ) 41-43 Okamoto, R. ( 1 9 ) 24 Okkuda, J. ( 2 ) 40 Okruszek, A . ( 2 0 ) 115, 116 Okuda, S. ( 2 0 ) 104 Okuda, T. ( 7 ) 27-29; ( 1 9 ) 83

289

Author Index Okumoto, T. ( 1 9 ) 65 Okunaka, R. ( 3 ) 25 Olano, A. ( 2 ) 43 O l a v i , P. ( 2 ) 52 O l e s k e r , A. ( 8 ) 3 , 5 ; ( 1 9 ) 27 Olson, J . A . ( 3 ) 49 Omichi, K. ( 4 ) 3 7 ; ( 9 ) 34 Onan, K. ( 2 3 ) 79 Ono, M. ( 7 ) 36 Onoda, T. ( 8 ) 15 Onoe, M. ( 7 ) 51 O p l e t a l , L. ( 1 6 ) 2 Orbe, M. ( 3 ) 127; ( 1 6 ) 3 5 ; ( 2 2 ) 62 Oremek, G. ( 1 5 ) 8 Ortuno, R.M. ( 2 4 ) 17-19 Oshikawa, T. ( 2 2 ) 69 Oshima, Y. ( 4 ) 45 Osmanaliev, M.K. ( 2 ) 5 Oswald, A.S. ( 2 ) 3 9 ; ( 3 ) 112 Otake, N. ( 1 9 ) 2 9 , 30, 4 0 , 43 Otani, S. ( 1 4 ) 14 O t a t a n i , N. ( 1 3 ) 3 0 ; ( 1 6 ) 51 O t s u k i , N . ( 1 9 ) 40 O t t , A.Ya. ( 6 ) 14 Ouedraogo, A. ( 2 1 ) 6 O u t c a l t , R.J. ( 3 ) 29 O u t t e n , R.A. ( 3 ) 172 Ovodov, Yu.S. ( 5 ) 2 ; ( 1 4 ) 17 Ozaki, S. ( 1 8 ) 5 8 , 9 9 , 100

.

Paddison, J. R. , j u n ( 2 2 ) 37 Padyukova, N.S. ( 1 7 ) 3 P a e g l e , R.A. ( 2 0 ) 83 Paez, M. ( 2 ) 4 3 ; ( 2 3 ) 9 P a g l i a r i n , R. ( 8 ) 11 P a i s , M. ( 9 ) 1 0 ; ( 1 4 ) 4 P a l a c i o s A l b a r r a n , J.C. ( 9 ) 5 , 7 1 ; ( 1 0 ) 22 P a l c i c , M.M. ( 3 ) 66 PaPecek, J. ( 7 ) 21 P a l l a r e s , I . ( 1 8 ) 34 Pan, C.H. (19) 6 9 , 7 0 Pandey, J . D . ( 2 ) 37 P a n d i t , U.K. ( 2 4 ) 73 P a n f i l , I. ( 1 4 ) 3 2 ; ( 2 4 ) 87 Pang, Y. ( 2 ) 6 0 ; ( 1 6 ) 5 7 , 58 Pankiewicz, K.W. ( 2 0 ) 2 9 , 6 4 , 8 5 , 87 Panossian, C.A. ( 4 ) 1 6 , 1 7 , 29 Panza, L. ( 3 ) 3 , 1 3 9 ,

1 6 5 ; ( 4 ) 23 Papageorgiou, C. ( 2 0 ) 44 P a p a h a t j i s , D.P. ( 2 4 ) 46 Paramonov, N.A. ( 2 2 ) 8 P a r a n j p e , M.G. ( 1 0 ) 16 P a r k , M.H. ( 5 ) 1 7 ; ( 2 2 ) 109 P a r k a n y i , L. ( 1 1 ) 1 1 ; ( 2 2 ) 45 Parmar, A. ( 2 ) 55 P a r o l i s , H. ( 7 ) 6 7 ; ( 1 0 ) 28 P a r o n i , R. ( 2 3 ) 73 P a r r i s h , F.W. ( 2 3 ) 8 6 P a r s o n s , R . ( 2 ) 50 Parvez, H. ( 2 3 ) 82 P a s c u a l , C. ( 1 8 ) 25 P a s h a l i d i s , A. ( 9 ) 2 0 ; ( 1 0 ) 3 7 ; ( 1 4 ) 13 P a s t o r , A. ( 2 3 ) 1 1 Paszkiewicz, E. ( 9 ) 31 P a t e l , A. ( 1 7 ) 21 P a t e l , G. ( 5 ) 2 5 , 4 2 ; ( 8 ) 32; ( 9 ) 11; (13) 28; ( 1 4 ) 37 P a t e r l i n i , G. ( 2 2 ) 2 P a t e r s o n , A.R.P. ( 2 2 ) 89 Pathak, T. ( 2 0 ) 55 P a t i l , V.J. ( 5 ) 43; ( 9 ) 1 8 ; ( 1 5 ) 13 P a t r o n i , J.J. ( 7 ) 7 5 ; ( 8 ) 37 P a t r z y c , H.B. ( 2 0 ) 39 P a t t , H. ( 7 ) 30 P a u l s e n , H. ( 3 ) 6 0 ; ( 4 ) 1 , 1 8 , 1 9 , 21, 31, 36; ( 7 ) 32; (18) 67, 75, 78, 79; (19) 46; (21) 3 1 , 53 Pauwels, R. ( 2 0 ) 5 3 , 60 P a v i a , A.A. ( 7 ) 33 Pawar, S.M. ( 5 ) 8 , 4 3 ; ( 9 ) 1 2 ; ( 2 4 ) 94 Payne, S . ( 3 ) 6 1 ; ( 1 8 ) 60-62 Payne, T.L. ( 2 4 ) 7 0 Pazur, J . H . ( 2 ) 44 Peach, J.M. ( 5 ) 4 1 ; ( 1 8 ) 38; (22) 52; (24) 76, 80 P e a r o v i c , J. ( 1 6 ) 1 P e a t , R. ( 2 ) 50 Pedersen, C . ( 9 ) 1 9 ; ( 1 3 ) 2 ; ( 2 4 ) 21 Pedersen, E.B. ( 9 ) 25-27, 28 Pedersen, H. ( 3 ) 5 7 ; ( 1 2 ) 3 P e i , Y. ( 7 ) 15 P e i n , C.D. ( 2 2 ) 14 Pekarovicova, A. ( 1 6 ) 1 P e l c z e r , I. ( 2 0 ) 125

P e l y v a s , I. (1) 2 Penades, S. ( 5 ) 1 9 ; ( 6 ) 7 ; ( 1 8 ) 25 Peng, Q.J. ( 5 ) 2 7 ; ( 2 1 ) 23 Penn, G. ( 2 0 ) 98 Perdomo, G.R. ( 3 ) 1 1 5 ; ( 5 ) 1 6 ; ( 8 ) 42 P e r e r a , A.M.A. (17) 8 P e r e z , C.S. ( 3 ) 62 P e r e z Rey, R. ( 2 ) 42 P e r e z Rojas, A.M. ( 3 ) 176 P e r i c h e t , G. ( 2 0 ) 151 P e r l i n , A.S. ( 2 ) 4 5 ; ( 5 ) 2 7 ; ( 2 1 ) 23 Perlman, M.E. ( 2 0 ) 68 P e r l y , B. ( 2 1 ) 3 3 , 39 Peseke, K. ( 1 1 ) 6 ; ( 1 8 ) 4 7 , 48 Peshakova, L.S. ( 2 0 ) 128 Pessen, H. ( 1 6 ) 67 Peters, J.A. ( 7 ) 73; (16) 3 , 10; ( 1 7 ) 1 7 , 30 P e t e r s , T. ( 3 ) 1 0 2 ; ( 4 ) 3 6 ; ( 2 1 ) 3 1 , 53 P e t e r s , U. ( 1 8 ) 8 ; ( 2 4 ) 96 P e t e r s e n , E.B. ( 2 0 ) 8 P e t e r s o n , M.L. ( 2 ) 2 7 ; ( 8 ) 39 P e t e r s o n , T. ( 2 3 ) 51 P e t i t o u , M. ( 4 ) 3 9 ; ( 2 1 ) 39 Petit-Ramel, M. ( 2 0 ) 151 P e t r a k o v a , E. ( 2 1 ) 4 2 , 4 3 , 44 P e t r i e , C.R. ( 3 ) 1 3 1 ; ( 1 0 ) 43 P e t r o v , B. ( 2 3 ) 69 P e t r u s , L. ( 2 ) 14 P e t r u s o v a , M. ( 2 ) 14 P e t t e r s s o n , L. ( 2 4 ) 7 Pezzone, M.A. ( 1 8 ) 41 P f l e i d e r e r , W. ( 2 0 ) 1 4 , 2 6 , 105, 111-114 P h a d t a r e , S. ( 1 6 ) 45 P h i l l i p s , G. ( 1 9 ) 79 P i a s , M. ( 1 9 ) 34 P i c q , D. ( 8 ) 1 3 ; ( 9 ) 5 5 ; ( 2 3 ) 90 P i k u l , S. ( 1 3 ) 3 7 ; ( 2 4 ) 9 P i l o t t i , A. ( 4 ) 47 Pimenov, A.M. ( 2 3 ) 76 P i n i , D. ( 1 8 ) 2 6 ; ( 2 2 ) 106 P i n t e r , I. ( 1 0 ) 19 P i n t o , B.M. ( 4 ) 3 8 ; ( 2 1 ) 4 Pishchugin, F.V. ( 9 ) 4 7 , 48 P i s k o r z , C.F. ( 3 ) 67 P i v n i t s k i i , K.K. (8) 4 0

2 90 Pivovarenko, V.G. (3) 30 Pjrzanowski, J. ( 7 ) 78 P l a z a Lopez-Espinosa, M.T. (3) 176 P l i s o v a , E.Yu. ( 5 ) 2 P l u s q u e l l e c , D. ( 7 ) 13, 31 Pocsik, I . ( 2 1 ) 55 Poehland, B.L. (19) 69 P o g l i a n i , L. (21) 49 P o i s s o n , J. ( 7 ) 1 Polavarapu, P.L. ( 2 2 ) 4 P o l e t t o , J . F . ( 7 ) 81 P o l i s s i o u , M. (22) 5 P o l l e r , R.C. (17) 21 P o l l e x , A. (21) 31 Polo C o r r a l e s , F. ( 2 0 ) 9 1 Polonsky, J. ( 1 6 ) 1 Pomilio, A.B. (16) 49 Pompon, A. ( 2 3 ) 6 4 , 6 5 Pongracic, M. ( 9 ) 58 Ponpipom, M.M. ( 3 ) 122 Popp, J.L. ( 2 ) 9 Popsavin, V. ( 2 4 ) 66 Poss, A . J . (14) 7 ; ( 1 6 ) 64; (24) 23, 24 P o t e n z a , D. ( 9 ) 37 P o t t e r , B.V.L. ( 1 8 ) 91-95 P o t t i , G.G. ( 5 ) 36; ( 8 ) 9 Pougny, J . R . ( 2 4 ) 6 1 Pouyet, B. ( 2 0 ) 151 Pouzar, V. ( 3 ) 36 Pozsgay, V. ( 3 ) 6 4 , 118; (4) 13; (9) 2 P r a c e j u s , H. (17) 1 4 P r a d e r a Adrian, M.A. ( 9 ) 70 P r a e f c k e , K. (18) 63, 69 P r a h s t , A. ( 3 ) 83 Prajer-Janczewska, L. (15) 8 P r a l y , J . P . (8) 1 8 ; ( 2 1 ) 5 ; ( 2 2 ) 44 Pramanik, B.N. ( 1 9 ) 8 5 ; (22) 9 P r a t t , J.A.E. (22) 18; (23) 36 Preobrazhenskaya, M.N. (20) 17 P r e u s s , R. (3) 153 Prhavc, M. (20) 88 P r i c e , R.W. (20) 6 1 , 8 7 P r i e b e , W. (21) 8 P r i n g , B.G. ( 9 ) 1 7 P r i n g , B.P. (16) 21; (17) 4 Prome, D. (22) 11 Prome, J.C. (22) 11 P r o u t , K. (5) 41; (22) 52; (24) 76 P r o v a s o l i , A . (16) 52 P r u e t t , P.S. (20) 71

Carbohydrate Chemistry P r u s o f f , W.H. (20) 67; (22) 88 Puech-Costes, E. ( 2 3 ) 6 0 Pugashova, N.M. ( 7 ) 49 Q u a i l , J.W. ( 2 2 ) 8 9 Queneau, Y. ( 3 ) 10 Raap, J. (22) 35 Rabanal, R.M. (24) 32, 33 Raczko, J. (13) 37 Radatus, B. (18) 68 Radernacher, T.W. (21) 38, 58 Ragazzi, M. ( 1 6 ) 52 Rahman, A.U. ( 5 ) 28; ( 1 1 ) 25; (18) 52; ( 2 1 ) 18 Rahman, M.A.A. (10) 49 Rahman, M.D. (23) 93 RajanBabu, T.V. (18) 90 R a j a n i k a n t h , B. ( 1 1 ) 3 Rakahashi, T. ( 5 ) 1 5 Rake, J . B . (19) 69 Rakumatullaev, I. (10) 1 4 Ramaiah, M. ( 3 ) 154; (12) 7 ; (14) 20 Rarnasamy, K. (19) 59; ( 2 0 ) 16, 1 9 , 90 Ramos Montero, M.D. ( 1 0 ) 22 Rampal, J . B . ( 2 0 ) 129 R a n d a l l , S.K. (18) 2 3 Kanfranz, 5.M. ( 1 9 ) 22 Rao, A.V.R. (24) 9 1 Rao, B.N..N. (21) 56 Rao, E.V. ( 5 ) 1 Rao, M.V. ( 5 ) 31 Rao, N.U.M. (21) 26 Rao, P.N. ( 3 ) 37 Rao, P.S. (14) 1 8 Rao, S.P. ( 3 ) 114; ( 5 ) 1 4 Rao, V.S.R. ( 2 ) 6 Rapasova, L. (16) 1 Rapoport, I. ( 2 3 ) 76 Rashed, N. ( 1 0 ) 49, 56; (16) 69 Rashid, A . (14) 52 Rathbone, E.B. ( 2 ) 46 Rathmann, R. (19) 4 5 R a u t e r , A.P. (14) 4 Readshaw, S.A. (21) 7 Reddy, G.C.S. ( 1 9 ) 26 Reddy, M.P. (20) 129 Reddy, M.S. ( 2 ) 56 R e d l i c h , H. (24) 70 Redmond, J . W . ( 5 ) 44; (16) 33 Reese, C.B. (18) 97; (20) 139 Refn, S. ( 3 ) 69

Regberg, T. ( 2 0 ) 126 Regeling, H. ( 7 ) 10 Rehnberg, N . (24) 65 R e i l l y , P.J. ( 2 3 ) 86 Reimer, G . J . ( 5 ) 24 Reinhold, V.N. (22) 6 , 7 , 24; ( 2 3 ) 2 9 , 38 Reiochenbach, N.L. ( 2 0 ) 114 R e i t z , A.B. ( 3 ) 169; (24) 13 Remaud, G. (20) 123, 144 Rernberg, G. ( 3 ) 42 Renner, R. (3) 157; (16) 68 Reppucci, L.M. (23) 1 6 Revankar, G.R. ( 1 9 ) 5 6 , 59; (20) 5 , 1 6 , 19, 51, 90, 124; ( 2 2 ) 8 5 Rhee, R.P. ( 9 ) 46; (14) 15 R i c a r d , L. (22) 2 R i c h a r d s , G.N. (23) 48, 93 Richardson, A.C. (10) 36, 38; ( 1 4 ) 1 ; ( 2 4 ) 5 7 , 83, 8 4 Rico, M. ( 1 8 ) 51; (22) 7 3 Rinaudo, M. (17) 31 R i n e h a r t , K.L., j u n . ( 1 9 ) 19 Riordan, J . M . ( 2 0 ) 34 Ripmeester, J . A . ( 1 0 ) 26 Risch, B. ( 7 ) 1 6 Ritter, A. (3) 137; (10) 42 Rivero, R.A. ( 3 ) 76 R i v e t t , D.E.A. (13) 35; (22) 72 R i v o l a , G. ( 1 9 ) 32 Robarge, K.D. ( 3 ) 168 Robert-Gero, M. (19) 66 R o b e r t s , G.D. (19) 6 9 , 70 R o b e r t s , S.M. (20) 95-97; ( 2 2 ) 97; (23) 6 3 Robina Ramirez, I. (10) 21 Robins, M . J . (19) 55; (20) 11 Robins, R.K. (3) 131; (10) 43; (19) 56, 59; (20) 5 , 9, 16, 19-21, 51, 57, 9 0 , 120, 124; (22) 8 4 , 85 Robinson, G.C. (24) 56 Robles Diaz, R. (3) 176 Rocchi, R. ( 7 ) 3 4 R o c h e t t i , F. (3) 139 Roden, W. ( 8 ) 29 Rodriguez, A.M. (3) 3 7 Rodriguez, C. (10) 9 Rodriguez, M. (10) 9

291

Author Index Rodriguez, R. ( 1 7 ) 32 Rodriguez Amo, J.F. ( 6 ) 10 Rodwell, J . ( 1 8 ) 68 R o l l g e n , F.W. ( 2 2 ) 20; ( 2 3 ) 35 Roesyadi, A . ( 2 ) 4 Rohr, J. ( 1 9 ) 42 Rokach, J . ( 9 ) 21; ( 1 3 ) 5 ; ( 2 4 ) 60 R o l l i n , P. ( 2 4 ) 25, 61 Roman Galan, E . ( 1 8 ) 1 5 ; ( 2 0 ) 91 Romo, E. ( 2 0 ) 63 R o n c h e t t i , F. ( 3 ) 3 ; ( 4 ) 23 Rosemeyer, H. ( 2 0 ) 4 7 , 49 Rosen, R.T. ( 9 ) 7 Rosenwirth, B. ( 2 0 ) 43, 133 R o s s e l l , J.L.A. ( 3 ) 119; (11) 4 R o s s e t , R. ( 2 3 ) 17 R o s s i , C. ( 2 1 ) 49 Roush, W.R. ( 9 ) 43 Row, K.H. ( 2 3 ) 91 Roy, N . ( 4 ) 12 Roy, R. ( 3 ) 1 4 ; ( 1 6 ) 4 4 ; ( 2 1 ) 35; ( 2 2 ) 66 Rubbo, M. ( 2 2 ) 25 Ruecker, G . ( 3 ) 106 Ruiz-Poveda, S.G. ( 1 9 ) 8 Rumble, R.H. ( 2 3 ) 63 Rupp, R.H. ( 1 9 ) 26 R u s s e l l , J.A.G. ( 8 ) 22 RUSSO, G. ( 3 ) 3 , 139, 165; ( 4 ) 23 Rustum, A.M. ( 2 3 ) 70 Ruzicka, C . J . ( 4 ) 30 Ruzic-Toros, Z. ( 2 2 ) 36 Ryan, P . J . ( 2 3 ) 58 S a e n g e r , W. ( 2 2 ) 8 2 , 92 S a g e r , W. (10) 11 S a g i , G. ( 2 0 ) 94 Saha, M. ( 2 3 ) 79 Sahoo, S.P. ( 1 8 ) 4 Sahu, N . P . ( 2 2 ) 39 S a i t o , H. ( 3 ) 43 S a i t o , I. ( 2 0 ) 147 S a i t o , S . ( 1 9 ) 53 S a i t o , T. ( 7 ) 1 7 ; ( 1 9 ) 6 5 ; ( 2 0 ) 3 0 , 33 S a i t o , Y. ( 3 ) 3 2 ; ( 8 ) 41 Sakaguchi, N . ( 3 ) 98 S a k a i r i , N. (19) 14 S a k a k i b a r a , H. ( 1 9 ) 65 S a k a k i b a r a , T. ( 8 ) 34, 36; ( 9 ) 24; (10) 55; (11) 12, 13; (12) 5 ; ( 1 3 ) 25, 26; ( 1 4 ) 3 3 ;

(15) 7 Sakamoto, I. ( 9 ) 7 8 ; ( 1 9 ) 9 Sakamoto, M. ( 1 9 ) 25 Sakanaka, 0 . ( 1 9 ) 49 S a k a t a , K. ( 1 8 ) 56 S a k a t a , Y. ( 3 ) 136 Sako, M. ( 2 0 ) 30, 33 Sakuda, S . ( 1 8 ) 84 Sakuma, T. ( 2 0 ) 32 S a k u r a i , H. ( 3 ) 136 S a k u r a i , T. ( 2 2 ) 70 S a l a n s k i , P. ( 1 3 ) 8 ; ( 1 4 ) 30 Salem, N . , jun. ( 2 2 ) 1 7 ; ( 2 3 ) 37 S a l i n a s , A . E . (10) 10; ( 2 1 ) 15 S a l v a d o r i , P. ( 1 8 ) 26; ( 2 2 ) 106 S a l v e r d e , S . ( 1 6 ) 13 Sam, V. ( 1 0 ) 23 Samain, D. ( 2 3 ) 59, 60 Samaki, H. ( 2 ) 31 Samuelsson, B. ( 1 1 ) 15 Sanchez, A . ( 1 0 ) 9 Sanderson, P . N . ( 1 6 ) 53 S a n d h o f f , K . ( 3 ) 142 San F e l i x , A. ( 5 ) 3 9 ; (10) 4 4 ; ( 1 8 ) 18 Sanghvi, Y.S. ( 2 0 ) 5, 5 1 ; ( 2 2 ) 85 Sankaro Rao, K. ( 2 2 ) 33 Sano, H. ( 1 9 ) 73 Sano, T. ( 2 0 ) 38 S a n t i k a r n , S. (22) 7 , 24; ( 2 3 ) 29, 38 Sanz, J. ( 2 ) 4 3 ; ( 2 3 ) 9 Sanz T e j e d o r , A . ( 6 ) 10 S a r d a , P. ( 8 ) 3 ; ( 1 9 ) 27 S a r f a t i , S.R. ( 5 ) 5 ; ( 7 ) ’ 54; (23) 3 S a r k a r , A.K. ( 4 ) 12 S a r o l i , A. ( 3 ) 11; (16) 30 S a s a k i , K. ( 1 8 ) 5 9 ; ( 2 3 ) 87 S a s a k i , N. ( 1 8 ) 80 S a s a k i , T. ( 1 9 ) 5 4 ; ( 2 0 ) 77 Sasho, M. ( 3 ) 25 S a s t r y , D.L. ( 2 1 ) 21 S a s t r y , K.V. (5) 1 Sathyanarayana, B.K. ( 1 8 ) 106; ( 2 2 ) 103 S a t o , K. ( 9 ) 33; ( 1 4 ) 6 , 9 , 35 S a t o , S. ( 3 ) 2 0 ; ( 4 ) 11, 40; ( 7 ) 9 ; ( 1 6 ) 4 8 ; ( 2 2 ) 68 S a t o , T. ( 2 ) 26; ( 1 5 ) 14 S a t o , Y. ( 2 2 ) 70

Satsuma Bayashi, K. ( 2 2 ) 104, 105 Satyamurthy, N . ( 8 ) 31 Saunders, J.K. ( 2 1 ) 3 , 6 Savagnac, A . ( 2 2 ) 11 Savra-Calixto, F. ( 2 ) 4 3 ; (23) 9 Sawa, T. ( 1 9 ) 24, 25 Sawada, S. ( 2 3 ) 57 Saxena, M. ( 2 ) 5 5 , 64 S a y e r s , J . R . ( 2 0 ) 32 S a y r e , L.M. ( 2 ) 69 S a z e , K. ( 5 ) 10 S c a l a , A. ( 3 ) 129, 130, 160 Scalfi-Happ, C. ( 2 0 ) 137 Schanzenbach, D. ( 7 ) 19 S c h a r f , H.-D. ( 7 ) 26; ( 1 9 ) 84 S c h a t z , F. ( 2 0 ) 133 Schauble, J.H. ( 8 ) 6 Schauer, R. ( 7 ) 8 ; ( 1 6 ) 38, 4 6 ; ( 2 4 ) 85 Scherkenbeck, J . ( 1 9 ) 82 S c h i l d k n e c h t , H. ( 3 ) 28; ( 7 ) 80 S c h i n a z i , R.F. ( 2 0 ) 61 S c h l e g e l , H.B. ( 2 1 ) 4 S c h l e s s i n g e r , R.H. ( 1 2 ) 19 S c h l i c h t h o e r l , G. ( 2 4 ) 63 S c h l o e g l , K. ( 2 4 ) 100 S c h l u t e r , G. ( 1 8 ) 2 2 Schmelzeisen-Redeker, G. ( 2 2 ) 20; ( 2 3 ) 35 Schmid, W. ( 1 6 ) 45 Schmidlin, C. ( 9 ) 82 Schmidt, D. ( 1 4 ) 38 Schmidt, H. ( 2 3 ) 76 Schmidt, R.R. ( 3 ) 5 5 , 6 8 , 9 4 , 9 9 , 123, 133, 134, 153; ( 4 ) 35; ( 1 2 ) 23; ( 1 3 ) 4 ; ( 1 6 ) 29; ( 1 8 ) 6 6 , 71 S c h o e l l k o p f , U. (10) 48 Schottmer, B. ( 4 ) 26, 2 7 ; (14) 3 S c h o l t z , S . A . (16) 24; ( 1 9 ) 63 Schouten, A . ( 2 2 ) 90 Schraml, J. ( 2 1 ) 4 2 , 43, 44 S c h r o d e r , C. ( 1 6 ) 38 S c h r o t e r , D. ( 1 8 ) 3 ; ( 2 4 ) 93 Schuda, A.D. ( 1 4 ) 4 8 ; ( 1 8 ) 30; ( 2 4 ) 47 S c h u l l e r , A.M. ( 1 8 ) 43 S c h u l l e r , M. ( 4 ) 18 S c h u l t e , G. ( 8 ) 3 8 ; ( 2 2 ) 48; ( 2 4 ) 55 S c h u l t z , G. (21) 37

Carbohydrate Chemistry

292 S c h u l t z , M. (7) 32 Sch u lz, G. (3) 86; (8) 17; (13) 10 S c h u r i g , V. (24) 70 Schwald, W. (23) 26 Schwarting, W. (18) 14; (22) 71 Schwarz, W. (20) 43, 133 Schweda, E. (21) 22 S c o l a s t i c o , C. (9) 37 S e b a s t i a n , R . (22) 87 Sebek, O.K. (19) 44 Secch i, C. (23) 12 S e c r i s t , J . A . , I11 (20) 70, 92 S e e l a , F. (20) 46-49; (22) 92 Seguin, E. (19) 37 S e i b e r t , G. (19) 82 S e i f f e r t , U.B. (15) 8 S e i l e r , F.R. (7) 32 S e i t z , S.P. (24) 49 S e k i , T. (23) 55 S e k i h a c h i , J. (3) 25 S ek in e, M. (20) 128, 131 S e l k e , R. (17) 14 S e l n i c k , H.G. (3) 84; (24) 54 Senda, M. (16) 66 S erafin o wsk i, P. (20) 73; (22) 93 S e r i a n n i , A.S. (2) 15; (5) 4; (12) 16; (14) 12; (16) 4; (21) 14, 17 S e r i n o , A.J. (3) 150 S e r v i , S. (12) 25 S e s a r t i c , L. (7) 12 S e s h a d r i , R. (11) 3 S e t h i , S.K. (20) 39 S e t o , H. (19) 29, 30, 43 S e t o i , H. (18) 46 Seymour, L.C. (3) 167 Shah, R.N. (5) 16 Shang, H. (5) 23 Shank, R.P. (7) 70 Shannon, W.M. (20) 93 Shao, M.J. (2) 62 S h a r g h i , H. (20) 138 S h arifk an ov , A.Sh. (10) 7 Sharma, M. (5) 36; (8) 9 S h a r s h e n a l i e v a , Z.Sh. (9) 47, 48 Shashkov, A.S. (7) 77; (9) 74; (21) 45 Shaw, A. (20) 56 Shaw, G. (3) 47 Sh ealy , Y.F. (20) 92,. 101 S h e a r e r , M.C. (19) 69, 70 S h eid , B. (20) 58 S h e l d r i c k , G.M. (22) 43 Shen, J. (7) 15 S h en g eliy a , M.S. (10) 4

S hi ba, N. (3) 44, 80, 8 1 Shi ba, T. (3) 12, 41, 97, 98; (7) 37; (16) 32; (22) 46 Shi baev, V.N. (4) 16, 17, 29; (7) 48, 50, 61 S h i b a i , H. (19) 41, 78 S h i b a t a , Y. (17) 6, 7; (18) 82; (19) 16 Shigemoto, T. (9) 38 Shi get oh, N. (17) 1 S h i l l i d a y , F.B. (19) 44, 77 Shima, K. (10) 8 Shimada, E. (23) 15 Shimada, K. (23) 49 Shimada, N . (19) 53 Shimamoto, T. (3) 97, 98; (10) 8 Shimauchi, Y. (19) 25 Shimizu, C. (3) 91; (7) 43; ( 9 ) 61 Shimizu, F. (2) 22 Shimizu, T. (3) 87 Shimosake, A. (19) 29 Shing, T.K.M. (7) 20; (18) 45 Shingu, T. (7) 27, 29 Shinomiya, K. (23) 28 S h i o t a n i , N. (18) 100 S h i o z a k i , M. (14) 42 S h i r a h a t a , K. (19) 73 S h i t o r i , Y. (3) 20; (7) 9 Shi ve, C.Y. (8) 22 Shoemaker, H.E. (7) 3 S h r i v a s t a v a , S.K. (2) 54 Shugar, D. (20) 1 Shukl a, A.K. (2) 37; (7) 8; (16) 38 Shukl a, R.S. (16) 59, 60 Shukl a, S.N. (2) 57 Shun, P. (20) 63 S h u t a l e v , A.D. (20) 31 Shut o, S. (20) 108 S h v e t s , V.I. (18) 104 S i b r i k o v , Yu.1. (18) 104 S i c s i c , S. (18) 88 Sidamonidze, N.N. (16) 7, 8 S i d d i q u i , I.H. (17) 29 Sierns, W. (23) 76 S i l a e v , A.B. (19) 67 Sirnard, R.E. (23) 52 Simmonds, R . J . (14) 5; (18) 29 Simmons, O.D. (5) 36; (8) 9 Simonet, J. (2) 13; (11) 2 Simpson, R.C. (23) 67, 68 S i nay, P. (3) 85, 125; (4) 39; (7) 79; (16)

19; (17) 11 S i n c l a i r , H.B. (18) 53 Singh, A.K. (2) 55, 64 Singh, G. (24) 75 Singh, J. (3) 35, 35 Singh, M.P. (2) 64 Singh, R.B. (9) 33; (14) 9 Singh, R.K. (2) 64 Sinha y, P. (6) 15 Sinnw e ll, V. (7) 32; (21) 31, 53 Sinou, D. (3) 149 S i r t o r i , C.R. (23) 73 S i s o d i a , A.K. (2) 55, 64 S i t r i n , R.D. (19) 69, 70 S k r o b a l , M. (20) 133 S k r y d s t r u p , T. (11) 28 Sla w in, A.M.Z. (20) 95, 96; (22) 97 Slough, G.A. (17) 10 Smal, E. (19) 60 Small, G.W. (21) 1 Smiatacz, Z. (9) 31; (22) 55 Smith, A.B., I11 (3) 76-78; (19) 8 1 Smith, C.Z. (5) 47 Smith, G.V. (2) 19, 20 Smith, P.W. (9) 14; (18) 35-38; (24) 79, 80 Smith, R.H.A. (23) 74 Smith, T.H. (14) 22; (24) 72 Smith, V.H. (11) 19 S n i t s , J.M.M. (22) 35 Smuda, H. (24) 2 Smyth, M.S. (24) 24 Snada, S. (23) 32 Sna tz ke , G. (13) 18; (17) 9, 23; (22) 107, 108 Snyder, J . R . (5) 4; (12) 16; (14) 12 Sobol, R.W., j u n . (20) 114 Sodano, G. (11) 23; (20) 72 S o f f e , N. (21) 38 Sokolov, V.M. (3) 110 Sokolowski, J. (16) 9; (18) 16; (22) 55 Soliman, A.A. (9) 7 S o l l , R.M. (24) 49 S o l l a d i e , G. (12) 22; (18) 1 Somogyi, A. (11) 11 Somogyi, L. (11) 10 Somsak, L. (11) 11; (22) 45 Son, J . C . (5) 41; (8) 12; (10) 3 1 Sondey, S.M. (23) 18, 19

Author Index Song, J. ( 1 8 ) 21 Sopin, V.F. ( 7 ) 77 Sosnovsky, G. ( 2 1 ) 26 Soulie, J. ( 1 8 ) 12 Sovova, M. ( 1 6 ) 2 Sowinski, P. ( 1 9 ) 38 Speranza, G. ( 3 ) 140 Spinelli, P.A. ( 1 9 ) 77 Spraviero, J.F. ( 2 1 ) 15 Springer, J.P. ( 3 ) 175 Sproviero, J.F. ( 1 0 ) 10 Squaldino, G. ( 2 2 ) 25 Srivastava, O.P. ( 3 ) 66, 71; ( 4 ) 6 , 7 ; ( 7 ) 58, 62 Stacey, N.A. ( 2 4 ) 56 Stawinski, J. ( 2 0 ) 106, 126 Stec, W.J. ( 2 0 ) 115-117 Steel, P.G. ( 2 4 ) 56 Steglich, W. ( 1 6 ) 1 8 ; ( 1 8 ) 49 Steiger, K.-M. ( 4 ) 31 Stein, H. ( 1 9 ) 82 Steker, H. ( 2 0 ) 46, 49 Stenhagen, G. ( 2 2 ) 22; ( 2 3 ) 34 Stepanov, A.E. ( 1 8 ) 104 Stepanska, B. ( 1 9 ) 39 Stephan, W. ( 1 8 ) 63, 69 Stephenson, L. ( 2 0 ) 95 Sterling, J. ( 2 ) 1 2 ; ( 7 ) 2 Sternfeld, F. ( 1 8 ) 57 Stetsenko, A.V. ( 2 0 ) 3 , 27 Stetter, K.O. ( 2 0 ) 127 Stevens, E.S. ( 1 8 ) 106; ( 2 2 ) 103 Stevens, J.D. ( 5 ) 45; (21) 3 Steyn, P.S. ( 3 ) 108; ( 1 5 ) 5 Stezowski, J.J. ( 1 4 ) 38 Sticher, 0. ( 2 3 ) 54 Stick, R.V. ( 7 ) 7 5 ; ( 8 ) 37; ( 1 7 ) 8 Stiem, M. ( 4 ) 19 Stocklin, G. ( 8 ) 28 Stoll, S . ( 7 ) 8 Stortz, C.A. ( 2 1 ) 13 Stoss, P. ( 1 8 ) 22 Straub, A. ( 7 ) 52 Straub, J.A. ( 9 ) 43 Street, I.P. ( 3 ) 31; ( 8 ) 19 Streicher, W. ( 2 0 ) 43 Streith, J. ( 9 ) 82 Strel'tsova, I.F. ( 6 ) 9 ; ( 9 ) 57 Stribblehill, P. ( 1 4 ) 5 ; ( 1 8 ) 29

2 93 Stromberg, R. ( 2 0 ) 106, 126

Struchkov, Yu.T. ( 7 ) 55 Studentsov, E.P. ( 3 ) 110 Sturgeon, R.J. ( 5 ) 1 Su, B. ( 5 ) 34 Suami, T. ( 9 ) 7 8 ; ( 1 4 ) 26; ( 1 8 ) 7 3 , 74, 7 6 , 77, 80, 82, 86, 87, 89; ( 1 9 ) 9-13, 49; ( 2 4 ) 81 Sudoh, R. ( 8 ) 34; ( 9 ) 24; ( 1 1 ) 12, 1 3 ; ( 1 2 ) 5 ; ( 1 3 ) 25, 26; ( 1 5 ) 7 Sugimoto, M. ( 3 ) 46, 92; ( 4 ) 11 Sugimoto, T. ( 2 3 ) 82 Sugiura, M. ( 2 2 ) 69 Sugiyama, H. ( 8 ) 25; ( 1 3 ) 9 Sugiyama, M. ( 2 2 ) 53 Suh, Y.-G. ( 3 ) 148; ( 2 4 ) 67 Suhadolnik, L. ( 2 0 ) 114 Suhadolnik, R.J. ( 1 9 ) 60; ( 2 0 ) 114 Sulton, P.A. ( 2 2 ) 86 Sumiyama, T. ( 7 ) 51 Sun, K.M. ( 3 ) 141 Sundaralingam, M. ( 2 2 ) 37 Sustmann, R. ( 1 2 ) 1 1 ; ( 2 2 ) 99, 100 Suvorov, N.N. ( 1 0 ) 4 Suyama, K. ( 2 3 ) 92 Suzuki, A. ( 1 8 ) 8 4 ; ( 1 9 ) 2 Suzuki, M. ( 3 ) 173, 174; ( 2 0 ) 81, 89 Suzuki, N. ( 2 0 ) 104 Suzuki, S. ( 1 8 ) 33; ( 2 3 ) 84 Suzuki, Y. ( 4 ) 4 ; ( 9 ) 42; ( 2 0 ) 36, 37 Sviridov, A.F. ( 1 4 ) 25; ( 2 4 ) 42-45 Svoboda, J. ( 7 ) 21 Svoboda, V. ( 2 3 ) 77 Swanson, S.J. ( 1 9 ) 22 Szab6, L. ( 1 6 ) 34 Szafranek, J. ( 1 6 ) 9 ; ( 1 8 ) 16 Szarek, W.A. ( 8 ) 14; ( 9 ) 30; ( 1 1 ) 19 Szeja, W. ( 1 1 ) 8 Szilagyi, L. ( 8 ) 44; ( 1 0 ) 29; ( 2 1 ) 51 Sztaricskai, F. ( 1 ) 2 Szurmai, Z. ( 2 ) 2 ; ( 4 ) 41

Taba, K.M. ( 1 7 ) 18, 19 Tabushi, I. ( 4 ) 2 Tachimori, Y. ( 9 ) 24;

( 1 1 ) 12, 13; ( 1 2 ) 5 ; ( 1 3 ) 25, 26 Tacken, A. ( 4 ) 22; ( 2 2 ) 15; (23) 2 Tada, M. (5) 25; ( 1 3 ) 9 Tada, T. ( 3 ) 107; ( 1 5 ) 4 Tadano, K. ( 1 4 ) 26; ( 1 8 ) 73, 74, 7 6 , 77, 86, 8 7 , 89; ( 2 4 ) 81 Taga, T. ( 1 0 ) 3 ; ( 2 2 ) 54 Tagagaki, T. ( 1 8 ) 85 Taguchi, T. ( 2 ) 40; ( 1 8 ) 9 ; ( 2 4 ) 97 Tajima, K. ( 1 6 ) 50 Tajrnir, R. ( 2 ) 67 Tajmir-Riahi, H.A. ( 1 6 ) 62; ( 1 7 ) 24, 26-28 Takagi, Y. ( 8 ) 16; ( 1 9 ) 33 Takahashi, S. ( 1 9 ) 68 Takahashi, T. ( 3 ) 96; ( 7 ) 43-46; ( 8 ) 25; ( 9 ) 60-63; ( 1 3 ) 9 ; ( 2 2 ) 7 0 ; ( 2 3 ) 57 Takahashi, Y. ( 4 ) 42, 43, 49 Takai, I. ( 9 ) 24; ( 1 1 ) 12, 13; ( 1 2 ) 5 ; ( 1 3 ) 25, 26 Takaku, H. (20) 140 Takano, S. ( 2 4 ) 1 1 , 12 Takaoka, D. ( 3 ) 107; ( 1 5 )

4 Takasaki, S. ( 2 3 ) 42 Takase, S. ( 1 9 ) 72 Takatsu, T. ( 1 9 ) 68 Takayama, H. ( 5 ) 38; ( 1 9 ) 57, 61

Takayanagi, H. ( 1 6 ) 48; ( 2 2 ) 68

Takeda, R. ( 5 ) 1 7 ; ( 2 2 ) 109

Takeda, S . ( 2 0 ) 132, 142 Takegoshi, K. ( 2 1 ) 21 Takehjashi, Y. ( 1 9 ) 58 Takenaka, K. ( 2 0 ) 65 Takeno, H. ( 1 8 ) 46 Takenuki, K. ( 1 9 ) 54; ( 2 0 ) 77

Takeo, K. Takeuchi, Takeuchi, Takeuchi,

(4) 4, 5

K. ( 2 0 ) 82 M. ( 2 3 ) 42

T. ( 3 ) 174; ( 1 9 ) 24, 25, 40, 58; ( 2 2 ) 23; ( 2 3 ) 39; ( 2 4 ) 90 Taki, T. ( 1 9 ) 11 Takita, T. ( 1 9 ) 51-53 Tamada, Y. ( 2 2 ) 69 Tam Ha, T.B. ( 2 0 ) 152 Tamm, C. ( 2 0 ) 44 Tampa, K. ( 2 1 ) 55

Carbohydrate Chemistry

294 Tamura, 0. ( 9 ) 40 Tamura, Y. ( 3 ) 2 5 ; ( 9 ) 40 Tanada, K. ( 1 9 ) 24 Tanahashi, M. ( 3 ) 9 0 ; ( 9 ) 67

Tanaka, A . ( 2 4 ) 20 Tanaka, H. ( 5 ) 1 1 ; ( 2 0 ) 7 6 , 81

Tanaka, K. ( 2 3 ) 88 Tanaka, 0. ( 2 3 ) 33 Tanaka, S . ( 7 ) 38, 4 0 , 4 1 ; ( 9 ) 6 5 , 6 6 , 69 Tanaka, T. ( 1 4 ) 49, 5 0 ; ( 2 4 ) 35-40 Tanase, T. ( 2 ) 22, 24; ( 2 2 ) 70 Taniguchi, S . ( 1 6 ) 56 Tanji, M. ( 3 ) 155 Tan Phan Viet, M. ( 2 1 ) 6 Taqui Khan, M.M. ( 1 6 ) 59 Tarara, G . ( 1 4 ) 38 Taravel, F . R . ( 2 1 ) 2 Tashpulatov, O . A . ( 1 0 ) 14 Tatsuta, K. ( 1 9 ) 40 Tattershall, R.H. ( 2 0 ) 119 Tavanaiepour, I. ( 2 2 ) 34 Tavecchia, P. ( 8 ) 11 Taylor, G.E. ( 2 0 ) 119 Taylor, I.E.P. ( 1 8 ) 5 9 ; ( 2 3 ) 87 Taylor, R.B. ( 4 ) 10 Taylor, S . ( 1 8 ) 57 Teeaar, R. ( 2 1 ) 4 2 , 55 Tejada, J . ( 1 7 ) 32 Tempete, C . ( 1 9 ) 66 Terada, T. ( 2 0 ) 132 Terano, H. ( 1 9 ) 72 Thang, T.T. ( 8 ) 5 Thatcher, G . R . J . ( 2 0 ) 119 Theis, D.L. ( 2 3 ) 62 Theophanides, T. ( 2 2 ) 5 Therisod, M. ( 7 ) 4 Thiel, I.M.E. ( 1 0 ) 4 5 , 4 6 ; ( 2 1 ) 10-12 Thiem, J. ( 3 ) 8 3 ; ( 4 ) 2 6 , 27; ( 5 ) 7 ; ( 7 ) 6 0 ; ( 1 2 ) 6 ; (13) 2; (14) 3 Thomas, E.J. ( 2 4 ) 56 Thomas, R.L. ( 4 ) 20; ( 8 ) 7 Thomas-David, G. ( 2 0 ) 151 Tian, 2. ( 1 8 ) 21 Tietze, L.F. ( 3 ) 5 , 6 , 42 Tikhonov, Y.V. ( 2 3 ) 76 Tillequin, F. ( 1 9 ) 37 Tjoa, S.S. ( 4 ) 44 Tleukeeva, 2h.A. ( 1 0 ) 7 Toke, L. ( 9 ) 8 Toelle, R. (10) 48 Tomoskosi, I. ( 2 0 ) 94 Toguzov, R.T. ( 2 3 ) 76

Tollin, P. ( 2 2 ) 2 6 , 8 0 , 91

Toma, L. ( 3 ) 3 , 139; ( 4 ) 23

Tomasic, J. ( 7 ) 12 Tomasz, J. (20) 125 Tomic, S . ( 7 ) 1 2 ; ( 2 2 ) 36 Tomimura, A. ( 2 ) 40 Tomioka, M. ( 2 3 ) 15 Tomishi, T. ( 2 0 ) 35 Tomita, K. ( 2 2 ) 78 Tomizawa, S . ( 2 0 ) 102 Tomura, M. ( 2 0 ) 103 Tone, H. ( 1 9 ) 25; ( 2 4 ) 41 Torgov, V.I. ( 4 ) 1 6 , 1 7 , 29

Torihara, M. ( 1 9 ) 5 Torri, G. ( 4 ) 39 Tosch, W. ( 1 9 ) 80 Toth, G. ( 9 ) 8 ; ( 1 0 ) 19 Toth, J.E . ( 1 9 ) 21 Toufeili, I.A. ( 1 4 ) 1 Touwslager, F. ( 1 6 ) 25 Townsend, C . A . ( 1 8 ) 7 Townsend, L.R. ( 2 0 ) 8 6 , 8 8 ; ( 2 2 ) 21; ( 2 3 ) 78

Townsend, R.R. ( 8 ) 1 0 ; (9) 53 Toyoda, H. ( 2 3 ) 28 Toyokuni, T. ( 1 8 ) 8 2 ; ( 1 9 ) 19

Tranchepain, I. ( 2 4 ) 8 6 , 95

Traving, B.C. ( 8 ) 24 Traxler, P. ( 1 9 ) 80 Treanor, S.P. ( 2 0 ) 100 Trinh, M.-C. ( 2 4 ) 71 Trivedi, G. ( 3 ) 2 7 ; ( 7 ) 22

Tronchet, J . M . J .

(10) 47;

( 1 3 ) 33

Troshkov, M.L. ( 2 2 ) 8 Truesdell, S.E. ( 1 9 ) 44 Trujillo Perez-Lanzac , M. ( 9 ) 49

Trushkina, I . A . ( 1 4 ) 1 9 ; ( 2 2 ) 16

Tsai, P.K. ( 2 2 ) 10 Tsang, R . ( 1 4 ) 40 Tsapkina, E.M. ( 2 0 ) 7 5 ; ( 2 2 ) 83

Tsegenidis, T. ( 2 3 ) 30 Tseng, C.K.H. ( 2 0 ) 100 Tsubono, K. ( 6 ) 1 1 ; ( 7 ) 7 4 ; ( 1 1 ) 1 7 ; ( 1 2 ) 10 Tsuchida, T. ( 8 ) 15 Tsuchiya, T. ( 8 ) 1 6 ; ( 1 9 ) 6 , 33 Tsuda, T. ( 7 ) 74 Tsuda, Y. ( 6 ) 1 1 ; ( 1 1 ) 1 6 , 1 7 ; ( 1 2 ) 9 , 10 Tsuhako, M. ( 7 ) 51

Tsuji, T. ( 2 0 ) 65 Tsurumi, Y. ( 1 9 ) 72 Tu, C . ( 2 2 ) 31 Tuan, J.S. ( 1 9 ) 23 Turakhia, R.H. ( 2 0 ) 93 Turchin, K.F. ( 1 0 ) 4 Turecek, F. ( 1 6 ) 2 Turmo Fernandez, P. ( 1 0 ) 18

Tvaroska, I. ( 2 ) 7 , 8 ; ( 3 ) 117

Uchida, I . ( 1 9 ) 72 Uchida, Y. ( 2 3 ) 32 Udaka, S. ( 1 9 ) 78 Ueda, N. ( 2 4 ) 60 Ueda, S . ( 2 0 ) 108 Ueda, T. ( 1 9 ) 5 4 ; ( 2 0 ) 36-38,

7 7 , 108

Uematsu, Y. ( 1 8 ) 80 Uemura, F. ( 2 0 ) 134 Uenishi, J. ( 2 4 ) 46 Ueno, T. ( 2 4 ) 62 Ueno, Y. ( 1 8 ) 7 3 , 86 Uhlmann, E. ( 2 0 ) 111, 112 Ulgiati, S. ( 2 1 ) 49 Umezawa, A . ( 2 3 ) 31 Umezawa, H. ( 3 ) 4 3 ; ( 8 ) 15, 16; (19) 3 , 6 , 24, 25, 33, 40, 5 8 ; ( 2 4 ) 90 Umezawa, S . ( 8 ) 1 5 , 1 6 ; ( 1 9 ) 1 , 4 , 6 , 33 Umezawa, Y. ( 1 9 ) 58 Unemi, N. ( 2 0 ) 132, 142 Unger, F.M. ( 3 ) 8 6 , 8 8 , 9 0 ; ( 4 ) 1 9 ; ( 9 ) 67 Unkefer, C . J . ( 2 1 ) 40 Unkovskii, B.V. ( 2 0 ) 31 Upadhya, K.G. ( 2 0 ) 5 ; ( 2 2 ) 85 Urano, Y. ( 9 ) 79 Urata, T. ( 1 9 ) 40 Urpi, F. ( 9 ) 7 2 ; (LO) 35 Usov, A . I . ( 7 ) 77 Usui, T. ( 1 9 ) 4 Utarnura, T. ( 2 3 ) 40 Utkina, N.S. ( 7 ) 48 Utley, J.H.P. ( 5 ) 47 Uvarova, N.I. ( 3 ) 38, 39 Uznanski, B. ( 2 0 ) 115

Vacas, I . ( 1 8 ) 34 Vacca, J . P. ( 1 8 ) 9 6 , 98 Vaccari, G. ( 2 2 ) 25 Vaccaro, H.A. ( 3 ) 7 7 , 7 8 ; ( 1 9 ) 81

Vaeslla, A. ( 1 6 ) 39 Vaghefi, M.M. ( 2 0 ) 120 Vaidyanathan, C.S. ( 2 2 ) 33

295

Author Index Valnot, J.-Y. (7) 69 Valpuesta Fernandez, M. (13) 38 Valverde, S. (5) 22; (13) 22, 24, 32; - ( i 7 ) (24) 32, 33 van Aelst, S.F. ( 2 Van Bekkum, H. ( 2 ) 66; ( 7 ) 73; (16) 25; (17) 1 7 , 30 van Belle, H. (23) van Boeckel, C.A.A 31 Van Boom, J . H . (4) 46; (9) 13, 76; (22) 35 Vanderhaege, H. (20) 53 van d e r Marel, G.A. ( 4 ) 46; (9) 76 Van Der Veen, J.M. ( 9 ) 35 Van Duin, M. ( 7 ) 73; (16) 3, 10; (17) 17, 30 Van Dyk, M.S. ( 6 ) 4 ; (15) 1 1 ; (22) 65 Vanes, T. (11) 7 Van Halbeek, H. ( 7 ) 8 Van Heerden, F.R. ( 3 ) 108; (15) 5 van H e i j e n o o r t , J. (19) 82 van H e i j e n o o r t , Y. (19) 82 Van Wietmarschen, J.A.C. (22) 35 Varela, 0. (10) 50; (13) 15 Vasella, A. (10) 40, 42; (17) 2 ; (24) 8 5 Vashakmadze, N.S. ( 2 ) 11 Vaskuri, J. (2) 52 Vather, S. (24) 56 Vazquez, J.T. (22) 109 Veetneman, G.H. ( 4 ) 33, 46 Vega, R. (22) 74 V e i t h , H . J . (19) 31 Vekemans, J . A . J . M . (16) 1 4 , 23; (24) 1 5 Velasco, R. (15) 12 Velez C a s t r o , H. ( 2 ) 42 Venkateswara, M.A. (22) 33 Verdoorn, G.H. (13) 1 Verez-Bencomo, V. ( 3 ) 22, 62 Vesely, J. (20) 130 V e y r i e r e s , A . ( 4 ) 48 Vial, J.-M. (20) 123 Vigdorchik, M.M. (10) 4 Vignon, M.R. (21) 2 Vilarrasa, J. (9) 72; (10) 27, 35 Villanueva, V.R. (23) 8 5

Vilpo, J.A. (20) 1 Vince, R. (20) 93 Vinogradov, E.V. (22) 8 V i r t a n e n , I. (2) 52 Vishveshwara, S. (2) 6 Viswamitra, M.A. (22) 33 V i t k , J.P. (24) 70 V i t t o r i , S. (20) 10 Vlahov, I. (13) 1 8 ; (17) 23; (22) 108 Vleggaar, R. (3) 108; (15) 5 V l i e g e n t h a r t , J.F.G. ( 7 ) 8 VockovB, J. (23) 77 V o e l t e r , W. ( 8 ) 2, 8; ( 9 ) 3 ; (10) 33, 34 Vogel, C. ( 9 ) 56 Vogt, M. ( 8 ) 30 V o i t u r i e z , L. (22) 8 7 Von Der S a a l , W. (19) 31 von Deyn, W. (18) 67, 75, 78, 79 von I t z s t e i n , M. (7) 59 Votruba, I. (20) 130 V o t t e r o , P.J.A. (13) 3 Voyksner, R.D. (22) 19; (23) 71 Voznyi, Ya.V. ( 3 ) 33 V r i j e n s , I. (20) 86; (22) 21; (23) 78 Vukojevie, N . (16) 55 Vyplel, H. ( 8 ) 17; (13) 10

Wagenaars, G . N . (21) 31 Wagle, D.R. (9) 35 Waglund, T. (3) 127; (16) 35; (22) 62 Wakabayashi, S. (20) 107 Wakamatsu, K. ( 3 ) 104 Wakamatsu, T. (24) 34, 48 Wakasawa, T. (23) 49 Wakimiya, T. ( 3 ) 41 Walker, G.A. (20) 153, 154 Walker, P.A. (18) 23 Walker, R.T. (20) 32, 80 Walkinshaw, M.D. (2) 47 Walser, M. (18) 3 ; (24) 93 Walton, D . J . (9) 30 Wan, A.S.C. (15) 2 Wanek, E. (20) 4 3 Wang, A.H.-J. (22) 94 Wang, Q. (5) 33; ( 7 ) 1 5 Wang, S. (3) 128 Wang, X. (20) 18 Wang, Y. (3) 159; (21) 48 Wanner, M . J . (24) 7 3 Ward, D.N. (23) 95

Ward, J . G . (18) 97 Warren, C.D. ( 4 ) 34 Watanabe, K.A. (20) 29, 61, 64, 68, 8 4 , 85, 87 Watanabe, S. (18) 8 4 Watanabe, T. (3) 32 Watanabe, Y. (18) 58, 99, 100 Watkin, D.J. (18) 38; (24) 8 0 Watson, G.M. (16) 22; (24) 22 Watson, W.H. (22) 34 ( 5 ) 37 Weber, A.J.M. Weber, E.J. (5) 20 Wegmann, B. (3) 55 Weichsel, A. (22) 28 Weigand, J. (4) 26; (14) 3 Weigrebe, W. (19) 20 Weinberger, R. (23) 23 Weinges, K. ( 3 ) 8 Weinreb, S.M. ( 9 ) 44, 45 Weinreich, R. (8) 30 Weissmiiller, J. ( 3 ) 152 Welch, J.T. (8) 1 Welzel, P. (18) 8 ; (19) 8 2 ; (24) 96 Wen, T. (23) 95 Werner, A . (23) 76 Werner, G. (20) 133 Westerduin, P. ( 4 ) 33 W h i s t l e r , R.L. (11) 25; (14) 1 1 ; (18) 28, 52 White, E. (10) 23 Whitesides, G.M. (12) 24 W h i t f i e l d , D.M. (4) 30 Whitney, R.A. (10) 41 Whittern, D.N. (19) 22, 23 Wichelhaus, J. ( 7 ) 30 Wichtl, M. (15) 3 Wickramage, C. ( 6 ) 3 Wiebe, L.I. (20) 62 Wiersum, U.E. (5) 37 Wiesler, W.T. (22) 109 Wiewi6rowski, M. (22) 79 Wightman, R.H. (24) 75 Wilbers, H. (9) 23; (14) 16 Wilckens, M. (14) 38 Wilcox, C.S. (3) 171 Wild, H. (16) 18; (18) 49 W i l e y , P.F. (19) 76 Wilkins, C.L. (16) 6 5 ; (22) 12 Wilkinson, C.P. (23) 44 Willard, N.P. (24) 7 3 W i l l i a m s , B.A. (13) 36 W i l l i a m s , D.J. (20) 95, 9 6 ; (22) 97 Williams, D.R. (12) 21

Carbohydrate Chemistry

296 William s, J.C. ( 2 2 ) 7 ; ( 2 3 ) 29 Williams, J.F. ( 7 ) 56 Williams, J.M. ( 1 8 ) 103 W i l l i a m s , N. (18) 81; (24) 6 Williams, W.M. ( 2 3 ) 72 Wilson, B.E. ( 3 ) 1 3 1 ; ( 1 0 ) 43 Wilson, C.C. ( 2 2 ) 26 Wilson, L. ( 2 ) 3 9 ; ( 3 ) 112 Winchester, B. ( 2 4 ) 81 Wincott, F.E. ( 3 ) 8 4 ; ( 2 4 ) 5 4 , 55 Wisniewski, A. ( 1 8 ) 16 Witczak, Z.B. ( 1 4 ) 1 1 ; ( 1 8 ) 28 Witczak, Z.J. ( 9 ) 4 ; ( 1 0 ) 1 3 ; (11) 1 W ith ers, S.G. ( 3 ) 3 1 ; ( 8 ) 19 W itzel, T. ( 1 2 ) 1 1 ; ( 1 4 ) 24; ( 2 2 ) 99 Wojtowicz, M. ( 1 0 ) 15 Wolf, A.P. ( 8 ) 22 Wolfe, S. ( 2 1 ) 4 Wolkanin, P.J. ( 2 0 ) 117 Wong, C.M. ( 1 9 ) 35 Wong, T.C. ( 8 ) 1 0 ; ( 9 ) 53 Wood, W.W. ( 1 4 ) 5 2 ; ( 1 6 ) 2 2 ; ( 2 4 ) 22 Woods, R . J . ( 1 1 ) 19 Wotring, L.L. ( 2 0 ) 8 6 ; ( 2 2 ) 2 1 ; ( 2 3 ) 78 Wray, V. ( 7 ) 16 Wright, G.E. ( 2 0 ) 50 Wu, C. ( 2 ) 1 8 ; ( 2 3 ) 6 Wu, E. ( 5 ) 34 Wu, H.Y. ( 1 4 ) 2 2 ; ( 2 4 ) 72 WU, J . 4 . ( 2 0 ) 54 wu, S.S. ( 4 ) 44 WU, T . 4 . ( 3 ) 158; ( 2 1 ) 2 8 , 47 Wu, T.T. ( 3 ) 29 Wu, X. ( 7 ) 25 Wulff, G . ( 2 ) 2 8 ; ( 7 ) 30 W y l e r , R. ( 1 6 ) 39 Wynants, J. ( 2 3 ) 6 9

Xie, F. ( 2 3 ) 49 Xing, X.K. ( 2 ) 62 Xu, C. ( 2 0 ) 1 8 Yadav, J.S. ( 2 4 ) 2 7 , 9 1 Yagi, A. ( 1 8 ) 56 Yakovlev, G.I. ( 2 3 ) 9 4 Yakunina, N.G. ( 2 0 ) 17 Yamabe, S . ( 1 6 ) 56 Yamada, H. ( 3 ) 1 0 3 ; ( 1 4 )

26 Yamada, K. ( 3 ) 1 0 4 ; ( 2 3 ) 82 Yamada, S. ( 2 4 ) 48 Yamada, T. ( 2 3 ) 57 Yamagata, Y. ( 2 2 ) 7 8 Yamagishi, Y. ( 1 9 ) 3 Yamaguchi, H. ( 2 3 ) 33 Yamaguchi, K. ( 8 ) 2 5 ; ( 1 3 ) 9 ; ( 2 0 ) 76 Yamaguchi, T. ( 2 0 ) 40 Yamaguchi, Y. ( 2 3 ) 55 Yamakage, S. ( 2 0 ) 1 1 0 , 134 Yamamoto, A. ( 9 ) 2 4 ; (11) 12, 13; (12) 5 ; (13) 25, 26 Yamamoto, H. ( 3 ) 1 4 7 ; (17) 1 Yamamoto, I. (19 ) 75 Yamamoto, M. ( 3 ) 9 7 ; ( 1 9 ) 2 4 , 61 Yamamoto, S. ( 2 4 ) 60 Yamamoto, Y. ( 2 1 ) 54 Yamane, H. ( 8 ) 21 Yamanoi, K. ( 3 ) 41 Yamaoka, S . ( 1 8 ) 99 Yamashita, J. ( 2 0 ) 132, 142 Yamashita, K. ( 2 4 ) 20 Yamashita, M. ( 2 2 ) 6 9 Yamauchi, H. ( 1 8 ) 56 Yamauchi, T. ( 1 5 ) 2 Yamaura, K. ( 2 ) 68 Yamazaki, M. ( 1 9 ) 4 7 , 48 Yamazaki, N. ( 9 ) 4 1 ; ( 1 8 ) 3 1 , 44 Yan, Y. ( 1 9 ) 35 Yan, Z.-Y. ( 2 1 ) 56 Yanagihara, Y. ( 3 ) 8 7 ; ( 2 3 ) 55 Yanamoto, K. ( 2 ) 68 Yang, C.L.C. ( 1 6 ) 6 5 ; ( 2 2 ) 12 Yang, C.M. ( 1 0 ) 41 Yanishevskaya, T.V. ( 2 0 ) 27 Yano, S . ( 2 ) 2 2 , 2 4 ; ( 2 2 ) 70 Yashunsky, D.V. ( 1 4 ) 2 5 ; ( 2 4 ) 42-45 Y a s i l l o , N.J. ( 8 ) 27 Yasuda, N. ( 1 9 ) 17 Yasukawa, K. ( 3 ) 109 Yasumoto, M. ( 2 0 ) 1 3 2 , 142 Yasuzawa, T. ( 1 9 ) 7 3 Yatabe, T. ( 8 ) 36 Yeh, H.J.C. ( 5 ) 3 5 ; ( 8 ) 4 , 2 0 ; ( 2 1 ) 29 Yeon, Y. ( 2 2 ) 3 2 , 75 Yergey, J . A . ( 2 2 ) 1 7 ;

( 2 3 ) 37 Yokoi, S. (19) 1 3 Yokoyama, S. ( 2 0 ) 128 Yokoyama, Y. ( 2 3 ) 46 Yonemitsu, 0. ( 1 4 ) 4 9 , 5 0 ; ( 2 4 ) 35-41, 58 Yoneta, T. ( 1 9 ) 6 Yoshida, M. ( 1 9 ) 7 3 Yoshida, S. ( 1 8 ) 8 0 Yoshida, T. ( 7 ) 1 7 , 2 8 , 29; ( 1 9 ) 83 Yoshikawa, M. ( 1 9 ) 5 Yoshikawa, S . ( 2 ) 22 Yoshikuni, Y. ( 2 2 ) 53 Yoshimoto, H. ( 1 9 ) 40 Yoshimura, H. ( 3 ) 9 7 , 98 Yoshimura, J. ( 3 ) 3 2 ; ( 8 ) 41; ( 9 ) 33; (14) 6 , 9 , 35 Yoshimura, S. ( 3 ) 20 Yoshimura, Y. ( 4 ) 5 0 ; ( 2 0 ) 35 Yoshino, K. ( 8 ) 36 Yoshioka, M. ( 2 3 ) 82 Yoshioka, T. ( 1 9 ) 25 Y os hiz a ki, M. ( 7 ) 27 Yosizawa, Z. (13) 30; ( 1 6 ) 51 Y o t s o j i , M. ( 2 0 ) 40 YOUdS, P. ( 2 0 ) 95-97; ( 2 2 ) 97 Young, R . A . ( 2 3 ) 7 Yoza, N. ( 7 ) 51 Yuan Ke, Y. ( 9 ) 40 Yurkevich, A.M. ( 2 ) 3

Za be l, V. ( 2 2 ) 92 Zahner, H. ( 1 9 ) 45 Z a i d i , S.A.H. ( 1 7 ) 29 Zak, 0 . ( 1 9 ) 80 Zakharov, V.I. ( 3 ) 110 Za ki, C. ( 2 2 ) 49 Zaman, N . ( 2 2 ) 27 Zamojski, A. ( 3 ) 5 2 ; ( 4 ) 9 ; ( 1 3 ) 34 Zamora Mata, F. (10) 1 8 , 21 Z a o r a l , M. ( 3 ) 9 5 ; ( 9 ) 59 Za rrine hz a d, M. ( 2 0 ) 138 Z b i r a l , E. ( 1 2 ) 4 ; ( 1 6 ) 4 5 , 4 6 ; ( 2 1 ) 37 Zee, J . A . ( 2 3 ) 52 Zeeck, A. ( 1 9 ) 42 Zeleny, J. ( 2 1 ) 44 Zemek, J. ( 7 ) 6 Zemlicka, .J. ( 1 9 ) 62 Zemlyakov, A.E. ( 3 ) 1 0 0 ; ( 7 ) 35 Zen, S. ( 5 ) 11 Zenk, R. ( 1 1 ) 22 Z e r b i , G. ( 2 2 ) 2

Author Index

Zercher, C.R. ( 3 ) 120 Zhang, F. ( 2 ) 59 Zhang, N. (18) 21 Zhang, Y. ( 2 ) 5 9 ; (24) 62 Zhao, S. (20) 18 Zhao, X. ( 2 ) 59 Zhbankov, R.G. (22) 3 Zhelyaev, V.M. (17) 16

297 Zhong, K. ( 9 ) 54 Zhou, X . (20) 143, 144 Z h u l i n , V.M. ( 3 ) 53, 54, 75 Z i e g l e r , J.-M. (23) 50 Z i e g l e r , S . J . (23) 54 Zimmerrnann, G . ( 1 9 ) 45 Zisser, L. (3) 7

Zou, R . (20) 11 Z o u l a l i a n , A. ( 2 ) 4 Z s e l y , M. (13) 27 Zsoldos-Mady, V. (12) 4 Zubkov, V.A. (14) 17 Z u l l i n o , G. (18) 26; (22) 106