Beat Ernst Gerald W. Hart Pierre Sinay

Carbohydrate sIn Chemistryand Biology

Part I

Chemistry of Saccharide s

Vol. 1

Chemical Synthesis ofGlycosides and Glycomimetics

Part I

Chemistry of Saccharides

Vol . 1

Chemical Synthesis of Glycosides and Glycomimetic s

List of Contributors LV

Abbreviations Used in Volumes 1 and 2 LXIII

I

Chemical Synthesis of Glycosides 1

1

Introduction to Volumes 1 and 2 3

2

Trichloroacetimidates 5Richard R, Schmidt and Karl-Heinz Jun g

2 .1

Introduction 52 .2

Methods 62 .3

O-Glycosides 72 .3 .1

Synthesis of Oligosaccharides 7ß-Glycosides, ß-Galactosides, a-Rhamnosides, etc 7Aminosugar Trichloroacetimidates 8ß-Mannosides 1 32-Deoxyglycosides 1 3Miscellaneous Compounds 1 4Complex Oligosaccharides 1 4

2 .3 .2

Inositol Glycosides 3 62 .3 .3

Glycosylation of Sphingosine Derivatives and Mimics 3 82 .3 .4

Glycosylation of Amino Acids 4 02 .3 .5

Polycyclic and Macrocyclic Glycosides 42

2 .3 .6

Glycosides of Phosphoric and Carboxylic Acids 442 .3 .7

Solid-Phase Synthesis 4 52 .4

S-Glycosides 492 .5

N- and P-Glycosides 5 12 .6

C-Glycosides 5 12 .7

Conclusion and Outlook 5 3References 5 3

3

Iterative Assembly of Glycals and Glycal Derivatives: The Synthesisof Glycosylated Natural Products and Complex Oligosaccharides . . . 6 1Lawrence J. Williams, Robert M. Garbaccio, and Samuel J.Danishefsky

3 .1

Introduction 6 13 .2

Ciclamycin 0 643 .3

Allosamidin 6 63 .4

KS-502 and Rebeccamycin 693 .5

Extension to Thioethyl Donors 743 .6

Lewis y 763 .7

Globo H 8 23 .8

KH-1 863 .9

Concluding Remarks 9 0Acknowledgments 9 0References 9 0

4

Thioglycosides 9 3Stefan Oscarson

4 .1

Introduction 9 34 .2

Synthesis of Thioglycosides 944 .2 .1

From Anomeric Acetates 944 .2 .2

From Glycosyl Halides 9 54 .2 .3

Protecting Group Manipulations in Thioglycosides 9 64 .3

Glycosylations with Thioglycoside Donors 974 .3 .1

A Two-Step Procedure : Transformation of Thioglycosides intoOther Types of Glycosyl Donors 97

4 .3 .2

Direct Activation of Thioglycoside Donors 9 9Heavy Metal Salt Promoters 9 9Halonium, sulfonium and carbonium type promoters 10 0Single-Electron Activation 10 6Other Types of Donors With an Anomeric Sulfur 108

4 .4

Applications of Thioglycosides 11 0

4 .4 .1

Block Syntheses, Orthogonal Glycosylations 11 0Thioglycosides as Acceptors 11 0Thioglycosides as Both Donors and Acceptors 11 1

4 .4 .2

Intramolecular Glycosidations 11 2

4 .4 .3

Solid Phase Synthesis 11 3References 113

5

Glycosylation Methods: Use of Phosphites 11 7Zhiyuan Zhang and Chi-Huey Won g

5 .1

Introduction 11 75 .2

Preparation of Glycosyl Phosphites 11 85 .3

Glycosylation using Glycosyl Phosphites 1195 .3 .1

Mechanism 11 95 .3 .2

Low Temperature-Dependent Stereoselectivity 12 15 .3 .3

Glycosylation of Sialyl Phosphites 12 25 .3 .4

Glycosylation of C-2-Acylated Glycosyl Phosphites 12 35 .3 .5

Glycosylation with C-2-O-Benzylated Glycosyl Phosphites 124Glycosylation using Glucosyl Phosphites with a Benzyl Group atC-2 124Glycosylation using Galactosyl and Fucosyl Phosphites with aBenzyl Group at C-2 12 5Glycosylation using other Glycosyl Phosphites with a Benzy lGroup at C-2 126

5 .3 .6

Glycosylation with 2-Deoxy Glycosyl Phosphites 12 75 .4

Other Applications of Glycosyl Phosphites 12 85 .4 .1

Synthesis of CMP-NeuAc 12 95 .4 .2

Synthesis of GDP-Fucose 1295 .4 .3

Formation of Glycosyl Phosphonate 13 15 .4 .4

Transformation to other Types of Glycosyl Donor 13 1Phosphate 13 1Phosphorimidate 13 1References 132

6

Glycosylation Methods : Use of n-Pentenyl Glycosides 13 5Bert Fraser-Reid, G. Anilkumar, Mark R. Gilbert, Subodh Joshi,and Ralf Kraehmer

6 .1

Introduction 13 56 .2

Fundamental Reactions 13 56 .3

Determination of Relative Reactivities 13 86 .4

n-Pentenyl Orthoesters as Glycosyl Donors 14 16 .5

n-Pentenyl Orthoesters as Latent C2 Esters 1446 .6

Protecting Groups 14 66 .7

Solid-Phase Iterative Couple-Deprotect-Couple Strategy 14 6References 15 3

7

Glycosylidene Diazirines 15 5Andrea Vasella, Bruno Bernet, Martin Weber, and WolfgangWenger

7 .1

Introduction 15 57 .2

Synthesis of Glycosylidene Diazirines 15 57 .3

Stability of the Glycosylidene Diazirines 15 87 .4

Glycosidation by Glycosylidene Diazirines 15 87 .4 .1

General Aspects 158

7 .4 .2

Glycosidation of Strongly Acidic Hydroxy Compounds 16 2Glycosidation of Phenols 16 2Glycosidation of Fluorinated Alcohols 16 3

7 .4 .3

Glycosylation of Weakly Acidic Hydroxy Compounds 16 3Glycosidation of Monovalent Alcohols 16 3Glycosidation of Diols and Triols 164

7 .5

Synthesis of Spirocyclopropanes 1687 .6

Addition to Aldehydes and Ketones 1707 .7

Exploratory Use of Diazirines : Formation of Glycosyl Phosphines ,Stannanes, N-Sulfonylamines, Esters, Boranes, and Alanes, and o f1,1-Difluorides 17 1Acknowledgments 174References 17 4

8

Glycosylation Methods: Alkylations of Reducing Sugars 17 7Jun-ichi Tamura

8 .1

Introduction 17 78 .2

Anomeric 0-Alkylation 17 78 .2 .1

Anomeric 0-Alkylation of Ribofuranose with Primary Triflates :Effect of the Protecting Group at 0-5 of Ribofuranose 17 8

8 .2 .2

Anomeric 0-Alkylation of Mannofuranose with Primary Triflates :The Crown Ether Effect 179

8 .2 .3

Anomeric 0-Alkylation of Gluco- and Galactopyranoses withPrimary Triflates : High [3-Selectivity as a Result of the ReactiveAnomeric (3-Anion 180

8 .2 .4

Anomeric 0-Alkylation of Acyl-Protected Nucleophiles wit hPrimary Triflates 18 1

8 .2 .5

Anomeric 0-Alkylation of Mannopyranose with Primary Triflates :Possibility of Intramolecular Complexation of the Nucleophile 184

8 .2 .6

Anomeric 0-Alkylation of KDO with Primary Triflates 18 58 .2 .7

Anomeric 0-Alkylation of Some Protected Aldoses with Primar yTriflate 18 6

8 .2 .8

Anomeric 0-Alkylation of Unprotected Aldoses with Primar yTriflate, Bromides, and Cyclic Sulfates 18 7

8 .2 .9

Anomeric 0-Alkylation with Secondary Triflates and Nonaflate 18 88 .3

Glycosylation via the Locked Anomeric Configuration 18 98 .3 .1

Synthesis of Methyl, Allyl, and Benzyl Glycosides via StannyleneAcetals 18 9

8 .3 .2

Epimerization at C-2 by the Locked Anomeric Configuratio nMethod 18 9

8 .3 .3

The Locked Anomeric Configuration Method for Rhamnosy lStannylene Acetal 190

8 .3 .4

The Locked Anomeric Configuration Method for Mannosy l

Stannylene Acetal : Isomerization of Acetal [25, 26] 190

8 .3 .5

The Locked Anomeric Configuration Method for Stannylen eAcetal with the Glucose Configuration [25, 26] 191

8 .4

Conclusion 192References 19 3

9

Other Methods of Glycosylation 19 5Luigi Panza and Luigi LayIntroduction and Summary 19 5Highlights 19 5

9 .1

Enol Ethers 19 79 .1 .1

Endo-Enol Ethers 19 89 .1 .2

Exo-Enol Ethers 20 19 .1 .3

Endo-Glycals 20 29 .1 .4

Exo-Glycals 2049 .1 .5

Vinyl Glycosides 20 69 .2

1-Hydroxy Sugars 2099 .2 .1

Acidic Activation 210Acidic Activation With Additional Reagents 21 1

9 .2 .2

Dehydrative Glycosylation 21 2In the Presence of the Acceptor From the Beginning 21 3

9 .2 .3

Mitsunobu Glycosylation 2149 .2 .4

1-0-Silyl Glycosides 21 59 .3

Esters and Related Derivatives 21 69 .3 .1

Esters 21 69 .3 .2

Sugar Carbonates and Derivatives 22 19 .3 .3

Orthoesters and Oxazolines 22 39 .3 .4

Phosphorus and Sulfur Derivatives 22 9References 23 3

10

Polymer-Supported Synthesis of Oligosaccharides 23 9Jiri J. Krepinsky and Stephen P. Douglas

10 .1

Introduction 23 910 .2

General Reflections 24 010 .3

Polymer Supports 24 610 .4

One-Phase Systems (Syntheses in Solution) 24 7Polyethyleneglycol.-monomethylether (MPEG) 24 8Linear Polystyrene 249

10 .4 .1

Linkers 250Succinoyl Diester 250Dioxyxylyl Diether (DOX) 25 2

10 .4 .2

Chemistry Investigations 25410 .5

Two-Phase Systems (Syntheses on Solid Supports) 25 5Controlled Pore Glass 256Cross-Linked Polystyrene 256Polyethylene Grafts on Cross-Linked Polystyrene 256

10 .5 .1

Linkers 259Dialkyl- or Diaryl-Silyl 25 9Thioglycoside Linkers 259

Linkers Cleavable by Photolysis 26 0

10 .6

Examples of Syntheses 26 0

10 .7

Combinatorial Libraries 26 1

10 .8

Capping 26 210 .9

Concluding Remarks 26 2

References 262

11

Glycopeptide Synthesis in Solution and on the Solid Phase 267Horst Kunz and Michael Schult z

11 .1

Introduction 26711 .1 .1

Which Protecting Groups are Suitable for Carbohydrate s(Table 2)? 269

11 .1 .2

Which Glycosylation Methods are Useful for the Formation o fGlycopeptides? 27 1Formation of Asparagine N-Glycosides 27 1a-Fucosylation 27 1Formation of the ß-Lactosamine Linkage 27 2a-Sialylation 27 2

11 .1 .3

Glycopeptides Containing Particularly Sensitive Linkages 27 2Acid Sensitivity 27 3Base Sensitivity 27 3

11 .2

Synthesis of Glycopeptides in Solution 27411 .2 .1

0-Glycopeptides 274Glycopeptides Carrying N-Acetylgalactosamine (Tn-Antigen) 274Glycopeptides Carrying the T-Antigen (Gal-GaINAc) 276Glycopeptides Carrying the Sialyl T Antige n(NeuAca2,6[Galß1,3]Ga1NAc) 27 8Glycopeptides Carrying O-G1cNAc 279

11 .2 .2

N-Glycopeptides 280N-Glycopeptides Carrying Natural Saccharide Side-Chains 280N-Glycopeptides with Lewis-Type Saccharide Side-Chains 285

11 .3

Glycopeptide Synthesis on the Solid Phase 28611 .3 .1

0-Glycopeptides 287Glycopeptides Carrying N-Acetylgalactosamine (Tn-Antigen) 28 7O-Glycopeptides Carrying the T Antigen (Gal-Ga1NAc) 29 0O-Glycopeptides Carrying the Sialyl Tn Antigen (NeuNAc-a2,6 -GaINAc) 29 1O-Glycopeptides Carrying the 2,3-Sialyl T Antigen 29 3O-Glycopeptides Carrying O-GIcNAc Side-Chains 29 4O-Glycopeptides Carrying 0-Linked Fucose 29 5O-Glycopeptides Carrying a Sialyl Lewis Antigen Structure 296

11 .3 .2

N-Glycopeptides 297The Construction of N-Glycopeptide Libraries on the Soli dPhase 298Sequential N-Glycopeptide Synthesis on the Solid Phase wit hOligosaccharides from Natural Sources 299

11 .4

Conclusion 300References 30 0

12

Glycolipid Synthesis 30 5Hideharu Ishida

12 .1

Introduction 30 512 .2

Synthesis of Ganglio-Series Gangliosides 30 512 .2 .1

Retrosynthetic Analysis of Ganglioside GDIa 30 512 .2 .2

Preparation of Sialylgalactose Donor as Building Block 30 612 .2 .3

Construction of Oligosaccharide 30 812 .2 .4

Transformation of Oligosaccharide into Glycolipid 31 012 .3

Synthesis of Polysialo Ganglio-Series Gangliosides 31 112 .3 .1

Retrosynthetic Analysis of GQIb 31 312 .3 .2

Preparation of Building Block 31 312 .3 .3

Construction of Oligosaccharide 31412 .4

Conclusion 31 5References 31 6

13

Stereoselective Synthesis of ß-Mannosides 31 9Vince Pozsgay

13 .1

Introduction 31 913 .2

Chemical Methods 32 013 .2 .1

Glycosylation with Mannosyl Donors 32 0Mannosylation using Insoluble Promoters 32 0The Sulfonate Approach 32 2Intramolecular Mannosylation 324Other Mannosyl Donor-Based Methods 32 7

13 .2 .2

Epimerization of ß-Glucopyranosides at C-2 32 9The Oxidation-Reduction Approach 32 9Direct Inversion 32 9

13 .2 .3

The 2-Ulosyl Donor Method 33 113 .2 .4

Anomeric 0-alkylation 33 2Alkylation of 1-0-Metal Complexes 33 2The Stannylene Acetal Method 33 2

13 .2 .5

Miscellaneous Methods 33 3Radical Inversion of the Anomeric Chirality of a-D -M ann opyran osides 33 3Reductive Cleavage of Cyclic Orthoesters 33 4De nova Syntheses 33 4

13 .2 .6

2-Acetamido-2-deoxy-ß-D-mannopyranosides 33 513 .2 .7

Aryl ß-D-mannopyranosides 33 613 .2 .8

1-Thio-ß-D-mannopyranosides 33 613 .2 .9

ß-D-Mannopyranosylamines 33 713 .3

Enzymatic Synthesis 33 713 .4

Conclusions 33 8References 338

14

Special Problems in Glycosylation Reactions : Sialidations 34 5Makoto Kiso, Hideharu Ishida and Hiromi It o

14 .1

Introduction 34 514 .2

Sialidation by the Koenigs-Knorr Method 34 514 .3

Sialidation Using an Auxiliary Group at C-3 34714 .4

Sialidation Using 2-Thioglycosides, Xanthates, or Phosphites o fSialic Acids in Acetonitrile 349

14 .4 .1

Thioglycosides 34914 .4 .2

Xanthates and Phosphites 35 614 .4 .3

Reaction Mechanism 35 914 .5

Further Solutions to the Problem 35 914 .5 .1

Combination of C-3 Auxiliary and Sterically less Hindered Suga rAcceptors 35 9

14 .5 .2

Combination of C-3 Auxiliary and Specific Activation of th eAnomeric Center C-2 36 0

14 .5 .3

Thioglycoside of N,N-Diacetylneuraminic Acid and Combinatio nwith C-3 Auxiliary 36 3References 364

15

Special Problems in Glycosylation Reactions : 2-Deoxy Sugars 36 7Alain Veyrieres

15 .1

Introduction 36715 .2

Electrophilic Additions to Glycals : Mechanistic Aspects andApplications to the Synthesis of 2-Deoxyglycosides 368

15 .2 .1

Protonation of Glycals 36915 .2 .2

Enzyme-Catalyzed Additions to Glycals 37015 .2 .3

Halogenation of Glycals 37015 .2 .4

Bromo- and lodoalkoxylation of Glycals 37 2

15 .2 .5

Epoxidation of Glycals 37 7

15 .2 .6

Addition of Sulfur Based Electrophiles to Glycals 37 915 .2 .7

Addition of Selenium Based Electrophiles to Glycals 38 215 .3

The Cycloaddition Way to Glycosyl Transfer 38 4

15 .4

Fluoroglycosylation of Glycals 38 5

15 .5

Glycosyl Donors with a C-2 Heteroatom 38 6

15 .5 .1

2-Bromo-2-deoxyglycosyl bromides 386

15 .5 .2

2-Deoxy-2-(thiophenyl)-glycosyl fluorides 38 7

15 .5 .3

2,6-Anhydro-2-Thio-Glycosyl Donors 388

15 .5 .4

1,2-Di-O-Acetyl-(3-Hexopyranoses and N-FormylglucosamineDerivatives 392

15 .6

2-Deoxyglycosyl Donors 393

15 .6 .1

2-Deoxy-Hexopyranoses 394

15 .6 .2

Tert-Butyldimethylsilyl 2-Deoxyglycosides 394

15 .6 .3

1-O-Acyl- and Acetimidyl-2-Deoxy-Hexopyranoses 394

15 .6 .4

2-Deoxyglycosyl Bromides and Fluorides 395

15 .6 .5

S-(2-Deoxyglycosyl)phosphorodithioates 396

15 .6 .6

2-Deoxyglycosyl Phosphates, Phosphoramidites and Phosphites 39 715 .6 .7

2-Deoxy Thioglycosides 39 815 .6 .8

2-Deoxyglycosyl Sulfoxides 39915 .7

Other Approaches to 2-Deoxyglycosides 40015 .7 .1

Cyclization of Acyclic Sugars 40 115 .7 .2

Use of Alkoxy-Substituted Anomeric Radicals 402References 40 3

16

Orthogonal Strategy in Oligosaccharide Synthesis 407Osamu Kanie

16 .1

Introduction 40716 .2

Analysis of the Strategic Aspects of Oligosaccharide Synthesis 40 816 .2 .1

General Aspects 40 816 .2 .2

The Pursuit of Efficiency in Oligosaccharide Synthesis 40 816 .3

The Introduction of the Orthogonal Glycosylation Strategy 41016 .3 .1

Limitation of Current Concepts 41016 .3 .2

The Orthogonal Coupling Concept 41 216 .3 .3

What is Orthogonality Anyway? 41 316 .3 .4

Orthogonal Glycosylation and Solid-Phase Oligosaccharid eSynthesis 414

16 .4

The Orthogonal Glycosylation Strategy 41416 .4 .1

Orthogonal Chain Elongation of Homo-Oligosaccharides :Synthesis of Chito-Oligosaccharides [19] 414

16 .4 .2

Orthogonal Coupling for Hetero-Oligomer Synthesis [22] 41 816 .4 .3

Application to Polymer-Supported Synthesis [26] 42016 .5

Conclusions and Prospects 42 1Acknowledgments 424References 424

17

Protecting Groups : Effects on Reactivity, Glycosylatio nStereoselectivity, and Coupling Efficiency 427Luke G. Green and Steven V. Ley

17 .1

Introduction 42717 .2

Glycosidic Mechanism 42817 .3

Electronic and Torsional Effects 43017 .4

Influence of Protecting Group on Donor Reactivity 43 117 .5

Stereoselectivity : 43617 .5 .1

Neighboring-Group Participation 43 617 .5 .2

Reactivity Control 43 717 .6

Influence of the Protecting Group on the Acceptor 44 117 .7

Steric Effects on Glycosylation 44 317 .8

Conclusions 444Acknowledgments 44 5References 446

18

Intramolecular Glycosidation Reactions 449Jacob Madsen and Mikael Bois

18 .1

Introduction 44918 .2

Reactions in which the Tether Participates in the Reaction 45018 .2 .1

Tethering to the Glycosyl Donor 450Carbon Tethers 450Silicon Tethers 454

18 .2 .2

Tethering to the Leaving Group 45918 .3

Reactions in which the Tether does not Participate in the Reaction 45 918 .4

Conclusion 464References 465

19

Classics In Total Synthesis of Oligosaccharides an dGlycoconjugates 467Jean-Maurice Mallet and Pierre Sinay

19 .1

Introduction 46719 .2

Syntheses of Nod factors 46719 .2 .1

Introduction 46719 .2 .2

The K. C. Nicolaou Synthesis (1992) [3] 46819 .2 .3

The J .-M . Beau Synthesis (1994) [12] 47 119 .2 .4

The T . Ogawa Synthesis (1994) [16] 47519 .2 .5

The Y. Z. Hui Synthesis (1992) [18] 47719 .2 .6

Conclusion 48019 .3

Synthesis of the Antithrombin-Binding Pentasaccharide Sequence i nHeparin (1984) [19, 20] 480

19 .3 .1

Introduction 48019 .3 .2

An Overview of the Synthesis of the Protected Pentasaccharid e73 48 1

19.3 .3

Synthesis of the Disaccharidic Bromide Donor 68 48319.3 .4

Synthesis of the Disaccharidic Acceptor 69 48419.3 .5

Synthesis of the Protected Pentasaccharide 73 48419.3 .6

Synthesis of the Active Site of Heparin 48 519 .4

Total Synthesis of VIM-2 Ganglioside [31] 48 519.4 .1

Introduction 48 519 .4 .2

The Total Synthesis of VIM-2 a General Strategy 48619 .4 .3

Preparation of the Key Protected Octasaccharide 87 48719 .5

Epilogue 490References 49 1

II

Synthesis of Oligosaccharide Mimics 493

20

Synthesis of C-Oligosaccharides 495Troels Skrydstrup, Boris Vauzeilles, and Jean-Marie Bea u

20 .1

Introduction 49 520 .2

The Anionic Approach 49620 .2 .1

C5-Alkynyl Anions 496

20 .2 .2

CI-Glycal Carbanions 50 020 .2 .3

Anomeric Samarium Species 50 220 .2 .4

C-Branched Carbanions 50 620 .2 .5

C6-Phosphoranes 50 820 .3

The Radical Approach 51 120 .3 .1

Intermolecular Anomeric Radical Addition 51 120 .3 .3

Intramolecular Anomeric Radical Addition 51 320 .4

The Partial de Novo Approach 51 820 .5

The Cycloaddition and Rearrangement Approach 52 7References 52 8

21

Synthesis of Oligosaccharide Mimics : S-Analogs 53 1Jon K. Fairweather and Hugues Driguez

21 .1

Introduction 53 121 .2

General Synthesis 53 221 .2 .1

Preparation of Thioglycoses 53 21-Thioglycoses 53 22-, 3-, 4-, 5-, or 6-Thioglycoses 53 2Selective S-Deprotection of Thioglycoses 53 3Glycosylation Methods 534

21 .3

Establishment of 1,6-Thio Linkages 53 421 .3 .1

6-Thiodisaccharides 53421 .3 .2

6-Thiooligosaccharides 53 821 .3 .3

Branched Thiocyclodextrins 53 821 .4

Establishment of 1,4-Thio Linkages 54 121 .4 .1

1,4-Thiodisaccharides 54 1General Approaches 54 1SN2-Displacement on Triflates 54 1

21 .4 .2

1,4-Thiooligosaccharides 54 6Conventional Approaches 54 6Chemoenzymatic Approaches 54 8Michael Addition to Unsaturated Acceptors 549Solid-Support Synthesis 550

21 .5

Establishment of 1,3-Thio Linkages 55 121 .5 .1

1,3-Thiodisaccharides 55 1Conventional Methods 55 1Cyclic Sulfamidate and Aziridine 55 1

21 .5 .2

1,3-Thiooligosaccharides 55221 .6

Establishment of 1,2-Thio Linkages 55 321 .6 .1

1,2-Thiodisaccharides 55 3Conventional Methods 554Other Approaches 55 5

21 .7

Establishment of 1,1-Thio Linkages 55 721 .8

Establishment of Mixed Thio linkages 55 821 .9

Thiooligosaccharides and Proteins 55 821 .9 .1

The Conformation of Thiooligosaccharides in Solution 558

21 .9 .2

Enzyme-Substrate Interactions : 560a-Glucan-Active Enzymes 560ß-Glucan-Active Enzymes 56 1

21 .9 .3

Lectin-Ligand Interactions 56221 .10

Conclusion 56 2Acknowledgments 56 2References 56 2

22

Saccharide-Peptide Hybrids 56 5Hans Peter Wesse l

22 .1

Introduction 56 522 .2

Carbohydrate Amino Acids 56 622 .2 .1

Natural Carbohydrate Amino Acids 56 622 .2 .2

Synthetic Carbohydrate Amino Acids 56 722 .3

Amide-Linked Carbohydrate Polymers 57 222 .4

Amide-Linked Carbohydrate Oligomers 57422 .4 .1

Solution Synthesis 57422 .4 .2

Solid-Phase Synthesis 57 822 .4 .3

Biological Activity 57 922 .4 .4

Conformational Properties 58 2References 58 3

Index I 1