Table of Contents

Volume 1

1 General Principles 1

1.1 Structure and Conformation of 3 T. Bruce Grindley

1.2 General Properties, Occurrence, and Preparation of Carbohydrates 57 John F. Robyt

2 General Synthetic Methods 101

2.1 Reactions at Oxygen Atoms 103 Ana M. Gomez

2.2 Oxidation, Reduction, and Deoxygenation 179 Robert Madsen

2.3 Heteroatom Exchange 227 Yuhang Wang, Xin-Shan Ye

2.4 Anhydrosugars 271 Slawomir Jarosz, Marcin Nowogmdzki

2.5 C-C Bond Formation 305 Yuguo Du, Qi Chen, Jim Liu

2.6 C=C Bond Formation 343 Slawomir Jarosz, Marcin Nowogrodzki

2.7 Degradations and Rearrangement Reactions 375 Jianbo Zhang

Bibliografische Informationen digitalisiert durch http://d-nb.info/980124565 gescannt durch Table of Contents

3 Reactions 427

3.1 Glycosyl Halides 429 Kazunobu Toshima

3.2 Glycosyl Trichloroacetimidates 451 Richard R. Schmidt, Xiangming Zhu

3.3 Further Anomeric Esters 525 Kwan Soo Kim, Heung Bae Jeon

3.4 O-Glycosyl Donors 565 J. Cristobal Lopez

3.5 S-Glycosylation 661 Stefan Oscarson

3.6 Glycal Derivatives 699 Waldemar Priebe, Izabela Fokt, Grzegorz Grynkiewicz

3.7 Anomeric Anhydro Sugars 737 Nathan W. McGill, Spencer J. Williams

3.8 C-Glycosylation 755 Toshio Nishikawa, Masaatsu Adachi, Minoru Isobe

Volume 2

4 Monosaccharides 813

4.1 Monosaccharides: Occurrence, Significance, and Properties . . 815 Zbigniew J. Witczak

4.2 Monosaccharides and Polyols in Foods 841 Robert B. Friedman

4.3 De novo Synthesis of Monosaccharides 857 Pierre Vogel, Inmaculada Robina

4.4 Monosaccharides as Chiral Pools for the Synthesis of Complex Natural Compounds 957 Masaya Nakata Table of Contents XI

4.5 Monosaccharides as Scaffolds for the Synthesis of Novel Compounds 995 Paul V. Murphy, Trinidad Velasco-Torrijos

4.6 Monosaccharides as Chiral Auxiliaries and Ligands for Asymmetric Synthesis 1029 Kiichiro Totani, Kin-ichi Tadano

4.7 -Metal Complexes: Structural Chemistry of Stable Solution Species 1077 Thorsten Allscher, Peter Klufers, Peter Mayer

5 Oligosaccharides 1141

5.1 Oligosaccharides: Occurrence, Significance, and Properties .. 1143 Zbigniew J. Witczak

5.2 Sucrose and Related Oligosaccharides 1163 Gillian Eggleston

5.3 Oligosaccharides in Food and Agriculture 1185 Michelle E. Collins, Robert A. Rastall

5.4 Combinatorial Methods in Oligosaccharide Synthesis 1205 Katsunori Tanaka, Yukari Fujimoto, Shin-ichi Tanaka, Yasutaka Mori, Koichi Fukase

5.5 Polymer-Supported and Tag-Assisted Methods in Oligosaccharide Synthesis 1241 Katsunori Tanaka, Koichi Fukase

5.6 Stereoselective Synthesis of /?-manno-Glycosides 1279 Akihiro Ishiwata, Yukishige Ito

5.7 Selective a-Sialylation 1313 Hiromune Ando, Makoto Kiso

5.8 Enzymatic Glycosylation by Transferases 1361 Ola Blixt, Nahid Razi

5.9 Enzymatic Glycosylation by Glycohydrolases and Glycosynthases 1387 Julian Thimm, Joachim Thiem XII Table of Contents

6 Complex Polysaccharides 1411

6.1 Polysaccharides: Occurrence, Significance, and Properties ... 1413 James N. BeMiller

6.2 Starch: Structure, Properties, Chemistry, and Enzymology .... 1437 John F. Robyt

6.3 Cellulose and Associated Heteropolysaccharides 1473 Wolfgang G. Glasser

6.4 Gums and Related Polysaccharides 1513 James N. BeMiller

6.5 Bacterial Cell Wall Components 1535 Cynthia Ginsberg, Stephanie Brown, Suzanne Walker

7 Glycolipids 1601

7.1 Glycolipids: Occurrence, Significance, and Properties 1603 Otto Hoist

7.2 Synthesis of Glycolipids 1629 Masahiro Wakao, Yasuo Suda

7.3 Gangliosides in the Nervous System: Biosynthesis and Degradation 1671 Robert K. Yu, Toshio Ariga, Makoto Yanagisawa, Guichao Zeng

7.4 Chemical Synthesis of Glycosylphosphatidylinositol (GPI) Anchors and GPI-Linked Structures 1697 Zhongwu Guo, Lee Bishop

8 Glycoproteins 1733

8.1 Glycoproteins: Occurrence and Significance 1735 Valentin Wittmann

8.2 Glycoproteins: Properties 1771 Valentin Wittmann Table of Contents XIII

8.3 Biologically Relevant Glycopeptides: Synthesis and Applications 1795 Clay S. Bennett, Richard J. Payne, Kathryn M. Koeller, Chi-Huey Wong

8.4 Glycosylation Engineering of Glycoproteins 1859 Reiko Sadamoto, Shin-Ichiro Nishimura

8.5 Glycoprotein Analysis 1873 Daryl Fernandes, Daniel Spencer

Volume 3.

9 Glycomimetics 1885

9.1 Azaglycomimetics: Natural Occurrence, Biological Activity, and Application 1887 Naoki Asano

9.2 Carbasugars: Synthesis and Functions 1913 Yoshiyuki Kobayashi

9.3 Sulfur-Containing Glycomimetics 1999 Andreas Steiner, Arnold Stiitz, Tanja Wrodnigg

9.4 C-Glycosyl Analogs of Oligosaccharides 2021 Boris Vauzeilles, Dominique Urban, Gilles Doisneau, Jean-Marie Beau

9.5 Oligosaccharide Mimetics 2079 Hans Peter Wessel, Susana Dias Lucas

10 Key Technologies and Tools for Functional Glycobiology . .2113

10.1 Key Technologies and Tools for Functional Glycobiology: Introduction 2115 Shin-Ichiro Nishimura

10.2 Microarrays - A Key Technology for Glycobiology 2121 Yan Liu, Ten Feizi

10.3 Non-Natural Sugar Analogues: Chemical Probes for Metabolic Oligosaccharide Engineering . . 2133 Udavanath Aich, Kevin J. Yarema XIV Table of Contents

10.4 Glycomics and Mass Spectrometry 2191 Anne Dell, Jihye Jang-Lee, Poh-Choo Pang, Simon Parry, Mark Sutton-Smith, Berangere Tissot, Howard R. Morris, Maria Panico, Stuart M. Haslam

10.5 Informatics Tools for Glycomics: Assisted Interpretation and Annotation of Mass Spectra 2219 Alessio Ceroni, Hiren J. Joshi, Kai Maafi, Rene Ranzinger, Claus-W. von der Lieth?

11 Biosynthesis and Degradation 2241

11.1 Biosynthesis and Degradation of Mono-, Oligo-, and Polysaccharides: Introduction 2243 Iain B. H. Wilson

11.2 Molecular Basis for the Biosynthesis of Oligo- and Polysaccharides 2265 Iain B. H. Wilson, Christelle Breton, Anne Imberty, Igor Tvaroska

11.3 Polysaccharide Degradation 2325 Bruce A. Stone, Birte Svensson, Michelle E. Collins, Robert A. Rastall

12 Glycomedicine 2377

12.1 Novel Approaches for Glycodrug Discovery 2379 Hirosato Kondo

12.2 Biomedicine of Monosaccharides 2399 Helen M. I. Osborn, Philip G. Evans, Karel Bezouska

12.3 Structure and Function of Mammalian Carbohydrate-Lectin Interactions 2445 Kevin Anderson, David Evers, Kevin G. Rice

12.4 Multivalency in Protein-Carbohydrate Recognition 2483 Laura L. Kiessling, Travis Young, Todd D. Gruber, Kathleen H. Mortell

12.5 Biomedicine of Enkephalin-Derived Glycopeptide Analgesics . . 2525 Robin Poll

12.6 Antitumor and Antimicrobial Glycoconjugates 2545 Thisbe K. Lindhorst

12.7 Glycoside vs. Aglycon: The Role of Glycosidic Residue in Biological Activity 2589 Vladimir Kfen Table of Contents XV

12.8 Mucin-Based Vaccines 2645 Jonathan P. Richardson, Derek Macmillan

12.9 Polysaccharide-Based Vaccines 2699 Violeta Fernandez Santana, Yury Valdes Balbin, Janoi Chang Calderon, Luis Pena Icart, Vicente Verez-Bencomo

Appendix: Nomenclature of Carbohydrates 2725

Index 2839 1.1 Structure and Conformation of Carbohydrates

T. Bruce Grindley Department of Chemistry, Dalhousie University, Halifax, NS B3H 4J3, Canada [email protected]

1 Conformational Analysis 4 1.1 Introduction 4 1.2 Conformations of Cycloalkanes and Heterocycles 5 1.2.1 Conformations of Cyclohexanes 5 1.2.2 Conformations of Tetrahydropyran Derivatives 7 1.2.3 Conformations of Cyclopentanes and Tetrahydrofurans 11 1.3 Conformations of Monosaccharides 13 1.3.1 Conformations of Acyclic Carbohydrates 13 1.3.2 Conformations of Pyranoses 15 1.3.3 Conformations of Furanoses 28 1.3.4 Conformations of Septanoses 30 1.4 Conformations of Disaccharides, Trisaccharides, and Oligosaccharides 32 1.4.1 Conformations of Disaccharides 32 1.4.2 Conformations of Trisaccharides and Oligosaccharides 36 2 Physical Methods 37 2.1 Introduction 37 2.2 X-Ray Crystallography 37 2.3 NMR Spectroscopy 37 2.3.1 Chemical Shifts 38 2.3.2 Scalar Coupling 38 2.3.3 Dipolar Coupling 40 2.3.4 Nuclear Overhauser Effect 40 2.4 Circular Dichroism and Optical Rotatory Dispersion 42 2.5 Molecular Modeling 42 1.2 General Properties, Occurrence, and Preparation of Carbohydrates

John F. Robyt Laboratory of and Enzymology, Department of Biochemistry, Biophysics, and Molecular Biology, 4252 Molecular Biology Building, Iowa State University, Ames, IA 50011, USA jrobyt @ iastate.edu

1 General Properties and Occurrence of Carbohydrates 60 2 Carbohydrate Property of Optical Rotation of Plane Polarized Light 60 3 The Structures of Carbohydrates 61 3.1 The Simplest Carbohydrates 61 3.2 Analogues of D-Glyceraldehyde 62 3.3 The Formation of Carbohydrates Containing More than Three Carbons 62 3.4 Special Properties of Pentoses and Hexoses 63 3.5 D-Glucose: the Most Prominent Carbohydrate on the Earth 64 3.6 Occurrence of D-Erythrose, D-Ribose, and D-Xylose 66 3.7 Occurrence of Hexoses 68 4 Properties and Occurrence of D-Glucose 68 4.1 D-Glucose in the Free State 68 4.2 D-Glucose in the Combined State 68 4.2.1 Occurrence of D-Glucose Combined with D-Fructose, D-Galactose, and D-Glucose, and High-Energy D-Glucose Donors 69 4.2.2 Properties and Occurrence of Sucrose and Sucrose Oligosaccharides Containing D-Galactose 69 4.2.3 Properties and Occurrence of D-Glucose Combined with D-Galactose to Give Lactose and Higher Oligosaccharides 71 4.2.4 Properties and Occurrence of a-D-Glucose Combined with a-D-Glucose to Give a,a-Trehalose 72 5 Properties and Occurrence of D-Glucose in Polysaccharides and Cyclodextrins 72 5.1 Properties and Occurrence of Starch 72 5.2 Properties and Occurrence of Glycogen 74 5.3 Properties and Occurrence of Dextrans, Alternan, Mutan, and Pullulan 74 5.4 Properties and Occurrence of D-Glucose in Cyclic Dextrins 75 5.5 Properties and Occurrence of Cellulose 76 58 General Principles

6 Properties and Occurrence of Hemicelluloses 78 6.1 Properties and Occurrence of Pectin 79 7 Cellulose-like Polysaccharides Containing iV-Acetyl-D-Glucosamine and D-Glucosamine 79 7.1 Properties and Occurrence of Chitin 79 7.2 Properties and Occurrence of Chitosan 80 7.3 Properties and Occurrence of Af-Acetyl-D-Glucosamine andJV-Acetyl-D-Muramic Acid in Murein - The Bacterial Cell Wall 80 7.4 Properties and Occurrence of Glycosaminoglycans Composed of Amino Sugars and Uronic Acids 81 7.4.1 Hyaluronic Acid 81 7.4.2 Chondroitin Sulfate 81 7.4.3 Dermatan Sulfate 81 7.4.4 Keratan Sulfate 82 7.4.5 Heparan Sulfate 82 8 Polysaccharides Containing Uronic Acids That Have Some of Their Carboxyl Groups Inverted by a C-5 Epimerase to Give New Polysaccharides with New Properties 82 8.1 Heparin Sulfate 82 8.2 Alginates 82 9 Occurrence and Properties of Plant Exudate Polysaccharides 83 10 Occurrence of Carbohydrates in Bacterial Polysaccharides 84 10.1 Xanthan, a Water-Soluble Bacterial Polysaccharide 84 10.2 Pathogenic Bacterial Capsular Polysaccharides 85 11 Properties and Occurrence of D-Fructose in Polysaccharides 86 12 Properties and Occurrence of Sugar Alcohols 86 12.1 Glycerol 86 12.2 Properties and Occurrence of Free Sugar Alcohols, D-Glucitol, D-Mannitol, Ribitol, Xylitol, and D-Arabinitol 86 12.3 Sugar Alcohols in Teichoic Acids 87 13 Properties and Occurrence of Deoxy Sugars 87 14 Properties and Occurrence of Carbohydrates in Glycoproteins 88 15 Separation and Purification of Carbohydrates 90 15.1 Isolation and Purification of a-D-Xylopyranose from Corn Cobs 90 15.2 Isolation and Purification of Lactose from Milk 91 15.3 Analysis, Isolation, and Purification of Monosaccharides and Oligosaccharides... 91 15.4 Separation and Purification of Water-Soluble Polysaccharides 93 15.5 Separation and Purification of Water-Insoluble Polysaccharides, Starch and Cellulose 94 15.6 Separation and Purification of Cyclomaltodextrins 95 15.7 Release of Oligosaccharides from Glycoproteins 95 2.1 Reactions at Oxygen Atoms

Ana M. Gomez Instituto de Quimica Organica General, (CSIC), 28006 Madrid, Spain iqog 106 @ iqog.csic.es

1 Introduction 106 2 Reactions at Non-Anomeric Hydroxyl Groups 107 2.1 Alkylation Reactions: Ether-Type Protecting Groups 107 2.1.1 Methyl Ethers 107 2.1.2 Benzyl (Bn) Ethers 108 2.1.3 Substituted Benzyl Ethers Ill 2.1.4 Allyl and Related Ethers 116 2.1.5 Trityl (Tr) Ethers 118 2.1.6 2-Naphthylmefhyl (NAP) Ethers 119 2.1.7 Propargyl Ethers 119 2.1.8 o-Xylylene Ethers 119 2.2 Acetalation Reactions: Acetal-Type Protecting Groups 121 2.2.1 Cyclic Acetals 121 2.2.2 Acyclic Acetals 127 2.3 Acylation Reactions: Ester-Type Protecting Groups 129 2.3.1 Acetyl (Ac) and Benzoyl (Bz) Esters 130 2.3.2 Substituted Acetyl Esters 134 2.3.3 Pivaloyl (Piv) Esters 134 2.3.4 Levulinoyl (Lev) Esters 136 2.4 Carbonylation Reactions: Carbonate-Type Protecting Groups 137 2.4.1 Benzyl Carbonates (Cbz) 138 2.4.2 Allyl Carbonates (Aloe or Alloc) 138 2.4.3 Propargyl Carbonates (POC) 140 2.4.4 2,2,2-Trichloroethyl Carbonate (TrOC) 140 2.4.5 Fluoren-9-ylmethoxycarbonyl (Fmoc) Group 142 2.4.6 2-[Dimethyl(2-naphthylmethyl)silyl]ethoxycarbonyl (NSEC) Group 142 2.5 Silylation Reactions: Silyl-Type Protecting Groups 144 2.5.1 Silyl Ethers. General Aspects 144 2.5.2 rert-Butyldimethylsilyl (TBS or TBDMS) Group 146 2.5.3 terf-Butyldiphenylsilyl (TBDPS) Group 147 2.5.4 Triisopropylsilyl (TIPS) Group 148 2.5.5 1,1,3,3-Tetraisopropyldisiloxane (TIPDS) Group 149 2.5.6 Di-fert-butylsilylene (DTBS) Group 150 2.6 Phosphorylation Reactions 151 104 General Synthetic Methods

3 Reactions at the Anomeric Hydroxyl 153 3.1 Alkylation Reactions 153 3.1.1 Anomeric O-Alkylation and O-Arylation 154 3.1.2 Anomeric O-Dealkylation 156 3.2 Acylation Reaction 160 3.2.1 Anomeric O-Acylation 160 3.2.2 Anomeric O-Deacylation 164 3.3 Carbonylation and Thiocarbonylation of the Anomeric Hydroxyl 165 3.4 Silylation 167 3.5 Phosphorylation and Phosphitylation 167 2.2 Oxidation, Reduction, and Deoxygenation

Robert Madsen Department of Chemistry, Center for Sustainable and Green Chemistry, Technical University of Denmark, Lyngby 2800, Denmark [email protected]

1 Introduction 180 2 Oxidations 180 2.1 Oxidation at the Anomeric Center 180 2.2 Oxidation of Primary Alcohols to Aldehydes 185 2.3 Oxidation of Primary Alcohols to Carboxylic Acids 186 2.4 Oxidation of Secondary Alcohols to Ketones 190 2.5 Epoxidation, Dihydroxylation, and Azidonitration of Olefins 196 2.6 Bromination at Ring Positions 201 3 Reductions 202 3.1 Reduction at the Anomeric Center 202 3.2 Reduction of Carboxylic Acids to Primary Alcohols 203 3.3 Reduction of Ketones to Secondary Alcohols 204 3.4 Reduction of Oximes to Primary Amines 206 3.5 Hydrogenation of Olefins 209 4 Deoxygenations 211 4.1 Deoxygenation at the Anomeric Center 213 4.2 Deoxygenation of Primary Alcohols 214 4.3 Deoxygenation of Secondary Alcohols 216 2.3 Heteroatom Exchange

Yuhang Wang, Xin-Shan Ye The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd #38, Beijing 100083, China [email protected]

1 Introduction 228 1.1 Nucleophilic Substitution 229 1.2 Ring-Opening Reaction 234 1.2.1 Nucleophilic Ring Opening of Epoxides 234 1.2.2 Ring-Opening Reactions of Five/Six-Membered Rings 236 1.3 Addition Reaction 237 2 Introduction of Halogens 238 2.1 Displacement of Sulfonic Esters 238 2.2 Direct Displacement of Hydroxyl Groups 239 2.2.1 Application of Alkoxyphosphonium Salts 239 2.2.2 Application of Iminium Salts 242 2.2.3 Application of Chlorosulfates 243 2.2.4 Application of Diethylaminosulfur Trifiuoride (DAST) 245 2.3 Ring-Opening Reactions 246 2.3.1 Opening of Epoxide Rings 246 2.3.2 Opening of Sulfur-Containing Rings 248 2.3.3 Opening of Benzylidene Acetals 248 2.4 Addition to Unsaturated Sugar Derivatives 249 2.5 Radical Bromination Reactions 250 3 Introduction of Nitrogen 251 3.1 Nucleophilic Displacement Reactions 251 3.2 Opening of Epoxide Rings 252 3.3 Addition of Nitrogenous Reagents to Double Bonds 252 3.3.1 Addition to Glycals 252 3.3.2 Addition to Isolated Alkenes 254 3.4 Cyclization of Dialdehydes 255 3.5 Reduction of Ulose Oximes 256 3.6 Rearrangement Reactions 256 3.7 Miscellaneous Methods 257 4 Introduction of Sulfur and Selenium 258 4.1 Nucleophilic Substitutions 258 4.2 Opening of Epoxide Rings 259 4.3 Addition to Unsaturated Carbohydrates 259 228 General Synthetic Methods

4.4 Rearrangement Reactions 260 4.4.1 1,2-Migrations 260 4.4.2 Rearrangements 261 5 Introduction of Phosphorus 262 5.1 Nucleophilic Substitutions 262 5.2 Ring-Opening Reactions 264 5.3 Addition Reactions 265 5.3.1 Addition to Carbonyl Compounds 265 5.3.2 Addition to Isolated Double Bond 266 5.4 Coupling Reaction 266 2.4 Anhydrosugars

Slawomir Jarosz, Marcin Nowogrodzki Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland [email protected]

1 Introduction 272 2 Anomeric Anhydrosugars: Synthesis and Reactions 274 2.1 1,6-Anhydrosugars 274 2.1.1 1,6-Anhydrohexopyranoses 274 2.1.2 1,6-Anhydrofuranoses 279 2.2 Higher Anhydroaldoses and Anhydroketoses 279 2.3 1,2-Anhydrosugars 280 2.4 1,3- and 1,4-Anhydrosugars 283 3 Non-anomeric Anhydrosugars: Synthesis and Reactions 284 3.1 Sugar Oxiranes 284 3.1.1 2,3-Anhydrosugars 286 3.1.2 Exocyclic Epoxides 290 3.1.3 Rearrangement of Sugar Epoxides 291 3.2 Sugar Oxetanes, Oxolanes (THF), and THP Derivatives 292 4 Anhydronucleosides 295 5 Miscellaneous 297 6 Conclusion 301 2.5 C-C Bond Formation

Yuguo Du*, Qi Chen, Jun Liu The State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China [email protected]

1 Introduction 306 2 C-C Bond Formation by Means of Nucleophilic Additions 306 2.1 Addition of Organometallics to Carbonyl Sugar 306 2.2 Aldol-Type Condensations 308 2.2.1 Aldol Reactions 308 2.2.2 Aldol-Cannizzaro Reactions 309 2.2.3 Nitroaldol Condensations (Henry Reaction) 310 2.3 Wittig Reaction 312 2.4 Other Nucleophilic Additions 315 3 C-C Bond Formation by Metal or Metal Complex Mediated Reactions 317 3.1 Rhodium Complex Catalyzed Reactions 317 3.2 Indium-Promoted Reactions 318 3.3 Diiodosamarium-Mediated Reactions 321 3.4 Other Metal-Catalyzed Reactions 322 4 Radical Cyclization 324 4.1 Intramolecular Free Radical Cyclization 324 4.2 Intermolecular Free Radical Cyclization 329 5 Rearrangement and Cycle Additions 332 6 Other Methods 336 2.6 C=C Bond Formation

Slawomir Jarosz, Marcin Nowogrodzki Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland [email protected]

1 Introduction 344 2 General Methods of the Formation of the Double Bond 346 3 Monosaccharides with the Endocyclic Double Bond 350 3.1 2,3-Unsaturated Monosaccharides 350 3.2 3,4-Unsaturated Monosaccharides 352 3.3 4,5-Unsaturated Monosaccharides 353 3.4 Rearrangement Reactions of Unsaturated Sugars 354 4 Monosaccharides with the Exocyclic Double Bond(s) 358 4.1 5,6-Unsaturated Pyranosides (and 4,5-Unsaturated Furanosides) 361 5 Acyclic Unsaturated Sugars 363 6 Application of Unsaturated Sugars as Chirons 366 7 Miscellaneous 370 8 Conclusions 372 2.7 Degradations and Rearrangement Reactions

Jianbo Zhang Department of Chemistry, East China Normal University, 200062 Shanghai, China jbzhang @ chem.ecnu.edu.cn

1 Overview 376 2 Hydrolysis of Glycosides and Polysaccharides 377 2.1 Chemical Hydrolysis 377 2.2 Enzymatic Hydrolysis 379 3 Degradation of Free Sugars 381 3.1 Thermal Degradations 381 3.2 Acidic Degradations 383 3.3 Alkaline Degradations 383 3.4 Oxidative Degradations 384 3.5 Enzymatic Degradations 386 4 Rearrangement with Double Bond Shifts 387 4.1 [2,3]-Sigmatropic Rearrangements 387 4.2 [3,3]-Sigmatropic Rearrangements 389 4.2.1 Overman Rearrangement and Related Reactions 389 4.2.2 Modified Claisen Rearrangements 390 4.2.3 Hetero-Cope Rearrangements 391 4.3 Double Bond Inducing Ring-Closing Rearrangements 393 5 Ring Isomerizations 394 5.1 Ring Contractions 394 5.2 Ring Expansions 398 5.3 Ring Transformation 404 5.4 Ring-Opening Rearrangements 404 6 Miscellaneous Reactions 404 6.1 Ferrier Carbocyclization and Related Reactions 404 6.2 Anomerization and Related Rearrangements 408 6.3 Aromatization of Sugars 412 7 The Maillard Reaction 414 7.1 Mechanism of the Maillard Reaction 415 7.2 Chemistry of Biologically Significant Maillard Products 415 3.1 Glycosyl Halides

Kazunobu Toshima Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan [email protected]

1 Chemical Glycosylation of Glycosyl Bromide and Chloride 430 2 Chemical Glycosylation of Glycosyl Iodide 433 3 Preparation and Chemical Glycosylation of Glycosyl Fluoride 433 3.1 Preparation of Glycosyl Fluoride 433 3.2 Chemical Glycosylation of Glycosyl Fluoride 439 3.2 Glycosyl Trichloroacetimidates

Richard R. Schmidt*1, Xiangming Zhu2 1 Fachbereich Chemie, Fach M 725, Universitat Konstanz, 78457 Konstanz, Germany 2 School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland [email protected], [email protected]

1 Introduction 452 2 Glycosyl Donor Generation Through Anomeric-Oxygen Exchange Reactions 453 3 Direct Anomeric Oxygen Alkylation 453 4 Glycosyl Donor Generation Through Retention of the Anomeric Oxygen 455 4.1 Methodological Aspects 460 4.2 Glycoside Synthesis on Polymer Supports 469 5 Recent Applications of O-Glycosyl Trichloroacetimidates in Complex Oligosaccharide and GlycoconjugateSynthesis 482 5.1 Glycolipids 482 5.2 Glycosyl Amino Acids and Glycopeptides 488 5.3 Nucleoside and Nucleotide Glycosidation 493 5.4 Synthesis of Glycosaminoglycans 493 5.5 Cell Wall Constituents 498 5.6 Synthesis of Glycosylphosphatidyl Inositol Anchors 505 5.7 Glycosylation of Various Natural Products and Their Metabolites 510 5.8 Cyclooligosaccharides 514 5.9 C-Glycoside Synthesis 514 5.10 O-Glycosyl Trichloroacetimidates of N,O- and S,O-Halfacetals 515 6 Related Activation Systems 516 7 Conclusions 517 3.3 Further Anomeric Esters

Kwan Soo Kim, Heung Bae Jeon Center for Bioactive Molecular Hybrids and Department of Chemistry, Yonsei University, Seoul 120-749, Korea [email protected]

1 Introduction 526 2 Glycosylation with Glycosyl Acetates 526 3 Glycosylation with Donors Having Other Anomeric Ester Groups 544 4 Glycosylation with Glycosyl Carbonates and Related Donors 551 5 Intramolecular Glycosylation Through 1-O-Acyl Linkages 556 6 Glycosylation with Donors Having Remote Acyl Groups 558 3.4 0-Glycosyl Donors

/. Cristobal Lopez Instituto de Quimica Organica General, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain clopez @ iqog.csic.es

1 Introduction 56g 2 «-Pentenyl Glycosides 570 2.1 Introduction 570 2.1.1 The Origin of w-Pentenyl Glycosides (NPGs) 570 2.1.2 Chemoselective Liberation of the Anomeric Group in NPGs 571 2.2 NPGs as Glycosyl Donors 571 2.2.1 Acyl-Substituted NPG Donors 573 2.3 Armed-Disarmed Strategy for Glycosyl Coupling 574 2.3.1 Mechanistic Aspects of the Oxidative Hydrolysis of NPGs 575 2.3.2 Evidence for }ntermo)ecu]ar Ha)onium-lon Transfer 576 2.3.3 Intermolecular Halonium-Ion Transfer: A Key Factor in the Implementation of the Armed-Disarmed Protocol 576 2.3.4 Torsional Disarming of NPGs 577 2.3.5 Sidetracking of NPGs: A Reversal for the Armed-Disarmed Strategy 578 2.4 Conversion of NPGs to Other Glycosyl Donors 580 2.4.1 Conversion to Glycosyl Bromides 580 2.4.2 Conversion to Glycosyl Phosphates 580 2.4.3 Conversion to Glycosyl Fluorides 580 2.4.4 Chemoselective Liberation Followed by Anomeric Activation 580 2.5 NPGs in the Stereocontrolled Assembly of a- and fi- Glycoproteins 580 2.5.1 Pyranosylacetonitrilium Ions from NPGs 580 2.5.2 Synthesis of iV-a-Linked Glycoproteins from Pyranosylacetonitrilium Ions 581 2.5.3 Synthesis of iV-jS-Linked Glycoproteins from Pyranosylacetonitrilium Ions 582 2.6 n-Pentenyl 2-Amino-2-Deoxy Glycoside Derivatives as Glycosyl Donors 583 2.7 Semi-Orthogonal Couplings of NPGs 587 2.7.1 Semi-OrthogonaJity of O-Penteny] and S-Ethyl Glycosides 587 2.7.2 Semi-Orthogonality of NPGs and Glycosyl Fluorides 588 2.8 n-Pentenyl Furanoside Donors 589 2.8.1 Chemoselective Deprotection of the Anomeric Center 589 2.8.2 Application to the Synthesis of Nucleosides 590 2.8.3 n-Pentenyl Furanosides as Glycosyl Donors 590 2.8.4 n-Pentenyl Arabinofuranosides in the Assembly of Oligoarabinans of Mycobacterium tuberculosis 591 2.8.5 Intramolecular Aglycon Delivery from n-Pentenyl Glycofuranosides 595 566 Chemical Glycosylation Reactions

2.8.6 Intramolecular C-Glycosylation of NPGs 595 2.8.7 NPGs of iV-Acetylneuraminic Acids (Neu5Ac) 596 2.8.8 NPGs of L-Iduronic Acid as Glycosyl Donors 596 2.9 NPGs in Regioselective Couplings 597 2.9.1 The Role of the 0-2 Substituent in Regioselective Couplings 597 2.9.2 Reciprocal Donor Acceptor Selectivity (RDAS) 598 2.9.3 In Situ Double Differential Glycosylations of Two Donors with One Acceptor . 599 2.10 The Origin of Regioselectivity in Three-Component Couplings 599 2.11 NPGs in Oligosaccharide Synthesis 601 2.11.1 The Pentasaccharide Core of the Protein Membrane Anchor Found in Trypanosoma brucei 601 2.11.2 The Nonamannan Component of High Mannose Glycoproteins 603 2.11.3 Synthesis of NodRf-in (C18:l) (MeFuc) 604 2.11.4 Synthesis of Phosphorylated Rat Brain Thy-1 Glycosylphosphatidylinositol Anchor 605 2.11.5 Synthesis of the Glycopeptidolipid of Micobacterium avium Serovar 4 608 2.11.6 Synthesis of Oligogalacturonates Based on NPGs 609 2.11.7 Miscellaneous 611 2.12 NPGs in Solid-Phase Oligosaccharide Synthesis 611 2.12.1 Glycosylation of Supported Alcohol Acceptors with NPG Donors 611 2.12.2 Pentenyl Glycoside-Based Linkers 612 2.13 Miscellaneous Uses of NPGs 614 2.14 Preparation of NPGs 614 3 Enol Ether-Type Glycosides 615 3.1 Early Contributions 615 3.2 Isopropenyl Glycosides 616 3.3 3-Butene-2-yl Glycosides as Precursors for Vinyl Glycosides 620 3.3.1 Latent-Active Glycosylation Strategy 620 3.3.2 Preparation of Trisaccharide Libraries 622 3.3.3 3-Buten-2-yl 2-amino-2-deoxy Glycosides as Glycosyl Donors 625 3.3.4 An Approach for Heparin Synthesis Based on 3-Buten-2-yl Glycosides 625 3.3.5 Conversion of 2-Buten-2-yl Glycosides to Other Glycosyl Donors 626 3.3.6 Synthesis of 3-Buten-2-yl Glycosides 626 3.4 Oxathiines: Vinyl Glycosyl Donors for the Synthesis of 2-Deoxy Glycosides... 626 4 DISAL Glycosyl Donors 626 4.1 Synthesis and Glycosylation Reactions 626 4.2 DISAL Donors in Solid-Phase Synthesis 628 4.3 Intramolecular Glycosylation Approach to the Synthesis of 1,4-Linked Disaccharides 628 4.4 Application of DISAL Donors to Oligosaccharide Synthesis 630 4.5 2-Deoxy-2-amino Derivatives as DISAL Donors 630 5 2'-Carboxybenzyl (CB) Glycosides 632 5.1 /?-D-Mannosylation Employing 2'-Carboxybenzyl Glycosyl Donors 633 5.2 Latent-Active Glycosylation Strategy 634 5.3 Stereoselective Construction of 2-Deoxyglycosyl Linkages 634 O-Glycosyl Donors 567

5.4 2'-Carboxybenzyl Furanosyl Donors. Acceptor-Dependent Stereoselective ^-D-Arabinofuranosylation 635 5.4.1 Synthesis of an Octaarabinofuranoside Based on Stereoselective a-D-Arabinofuranosylation 637 5.5 2'-(Allyloxycarbonyl)benzyl (ACB) Glycosides: New "Latent" Donor for the Preparation of "Active" 2-Azido-2-deoxy BC Glycosyl Donors 639 5.6 Synthesis of Oligosaccharides Based on BC Glycosyl Donors 640 5.6.1 Synthesis of Trisaccharide 431, the Repeat Unit of the O-Antigen Polysaccharide from Danish Helicobacter pylori Strains 640 5.6.2 Synthesis of Tetrasaccharide 438 641 5.6.3 Synthesis of Tetrasaccharide Repeat Unit from E. coli Oil 641 5.6.4 Total Synthesis of Agelagalastatin 643 5.7 Conversion of 2'-Carboxybenzyl Glycosides into other Glycosyl Donors 643 5.8 2'-CarboxybenzyI Glycosides as Glycosyl Donors for C-GIycosylation 644 6 0-Heteroaryl Glycosyl Donors 644 6.1 2-Pyridyl 2,3,4,6-tetra-O-benzyl-D-glucosides 644 6.2 O-Hetaryl Glycosides by Schmidt's Group 644 6.3 3-Methoxy-2-pyridyl (MOP) Glycosides 645 6.3.1 Coupling of Unprotected MOP Glycosyl Donors 645 6.3.2 Esterification and PhosphoryJation of Unprotected MOP Glycosides 646 6.3.3 MOP Glycosides in Oligosaccharide Synthesis 649 6.4 6-Nitro-2-benzothiazolyl Glycosides 649 7 Miscellaneous 0-Glycosyl Donors 651 3.5 S-Glycosylation

Stefan Oscarson Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm 106 9], Sweden stefan.oscarson @ ucd.ie

1 Introduction 662 2 Synthesis of Monothioglycosides 664 2.1 Direct Synthesis 664 2.1.1 From Anomeric Acetates 664 2.} .2 From HaJogen Sugars 666 2.1.3 From Hemiacetals 668 2.1.4 From Trichloroacetimidates 671 2.1.5 From Glycosides 671 2.1.6 From Glycals 673 2.1.7 From Anhydro Sugars 675 2.2 Indirect Synthesis 677 2.2.1 Via Glycosyl Thioacetates 677 2.2.2 Via Glycosyl Pseudothiouronium Salts 677 2.2.3 Via Glycosyl Thiocyanates 678 2.2.4 Via Glycosyl Xanthates 679 2.2.5 Via 1,2-Thiazoline Derivatives (2-Acetamido Donors) 680 2.2.6 Via Glycosyl Thioimidocarbonates and Diglycosyl Disulfides 680 2.3 Alkylation of Thioaldoses 681 2.3.1 Via Aryldiazonium Derivatives 681 2.3.2 By Addition to Alkenes 682 2.4 Miscellaneous Methods 682 2.4.1 Rearrangement of 1-Sulfenates 682 2.4.2 Rearrangement of Thioorthoesters 683 2.4.3 Rearrangement of p-Nitrobenzoylxanthatcs 6X3 3 Synthesis of Thiooligosaccharides 684 Glycosylations with Thiol Acceptors 6K4 . 1 Anhydro Sugars as Donors 684 .2 Trichloroacetimidates as Donors 6X5 •3 Glycals as Donors 685 .4 Base-Promoted Glycosylations 686 3.2 Displacement Reactions with 1-Thioglycoses 686 3.2.1 Formation of Anomeric Thiols 686 3.2.2 The Nature of the Electrophile (Leaving Group) 6S9 3.2.3 Solid-Phase Synthesis of Thiooligosaccharidcs 691 662 Chemical Glycosylation Reactions

3.2.4 Synthesis of Non-Reducing Sugars 691 3.2.5 Enzymatic Synthesis 691 3.3 Examples 693 3.7 Anomeric Anhydro Sugars

Nathan W. McGill, Spencer J. Williams* School of Chemistry, The University of Melbourne, Parkville, VIC 3052, Australia [email protected], [email protected]

1 Introduction 738 1.1 General Remarks 738 2 1,6-Anhydrohexopyranoses 738 2.1 Occurrence and Formation 738 2.2 Reactions 742 2.3 Cleavage 744 3 1,2-Anhydro Sugars 745 4 Miscellaneous Anhydro Sugars 747 4.1 1,3-Anhydro Sugars 747 4.2 1,4-Anhydropyranoses (1,5-Anhydrofuranoses) 748 4.3 1,6-Anhydrohexofuranoses 748 4.4 Levoglucosenone 749 5 Anhydro Sugars Containing Nitrogen, Sulfur, or Selenium 750 3.8 C-Glycosylation

Toshio Nishikawa, Masaatsu Adachi, Minoru Isobe Graduate School of Bioagricultural Sciences, Nagoya University, 464-8601 Nagoya, Japan [email protected], madachi @agr.nagoya-u.ac.jp, isobem @ agr.nagoya-u.ac.jp

1 Introduction 756 2 Nucleophilic Addition to Electrophilic Carbohydrate Derivatives 757 2.1 Lactol as an Electrophilic Carbohydrate 757 2.2 Lactone as an Electrophilic Carbohydrate 760 2.2.1 Reaction with Enolate and Related Anions 760 2.2.2 Reaction with Wittig Reagents and Related Reagents 761 2.2.3 Reaction with Organometallic Reagents Followed by Reduction of the Newly FormedHemiacetal 764 2.3 Glycosides (Halides, Oxygen, and others) as Electrophilic Carbohydrates 766 2.3.1 Reaction with Grignard Reagents and Organoaluminum Reagents 767 2.3.2 Reaction with Organosilane and Organotin Reagents 768 2.3.3 Aryl-C-Glycosylation with Aromatic Nucleophiles 771 2.4 Glycal as an Electrophilic Carbohydrate 776 2.5 Anhydrosugar as an Electrophilic Carbohydrate 780 3 Anomeric Radical Intermediate 785 3.1 Intermolecular Radical Reaction 785 3.2 Intramolecular Radical Reaction 789 4 Anomeric Anion 791 4.1 Lithium Anomeric Anion 791 4.2 Ramberg-Backlund Reaction 794 4.3 Samarium Anion Mediated Reactions 794 5 Sigmatropic Rearrangement 798 6 Transition Metal-Catalyzed Reactions 802