Carbohydrates: The Essential Molecules of Life, Second Edition

Front Cover......Page 1
Carbohydrates: The Essential Molecules of Life......Page 4
Copyright Page......Page 5
Table of Contents......Page 8
Preface and Acknowledgements......Page 18
Abbreviations......Page 20
The Early Years......Page 24
The Constitution of Glucose and Other Sugars......Page 30
The Cyclic Forms of Sugars, and Mutarotation......Page 38
The Shape (Conformation) of Cyclic Sugars, and the Anomeric Effect......Page 46
References......Page 55
CHAPTER 2: Synthesis and Protecting Groups......Page 58
Acetates......Page 59
Benzoates......Page 61
Levulinates......Page 62
Carbonates, borates, phosphates, sulfates and nitrates......Page 63
Sulfonates......Page 64
Methyl ethers......Page 65
Benzyl ethers......Page 66
4-Methoxybenzyl ethers......Page 67
Silyl ethers......Page 68
Acetals......Page 70
Cyclic acetals......Page 72
Benzylidene acetals......Page 73
4-Methoxybenzylidene acetals......Page 76
Isopropylidene acetals......Page 77
Diacetals......Page 80
Thioacetals......Page 81
Stannylene acetals......Page 82
The Protection of Amines......Page 84
Orthogonality......Page 89
References......Page 90
Oxidation......Page 98
Reduction......Page 103
Halogenation......Page 107
Non-anomeric halogenation......Page 108
Anomeric halogenation......Page 112
Non-anomeric alkenes......Page 116
Anomeric alkenes......Page 117
Carbocycles......Page 119
Anhydro Sugars......Page 121
Non-anomeric anhydro sugars......Page 122
Anomeric anhydro sugars......Page 124
Deoxy sugars......Page 128
Amino deoxy sugars......Page 130
Branched-chain sugars......Page 134
Wittig reaction......Page 135
Thiazole-based homologation......Page 136
Mitsunobu reaction......Page 137
Orthoesters......Page 138
D-Fructose......Page 140
Isomaltulose......Page 142
Lactulose......Page 143
Aza and Imino Sugars......Page 144
References......Page 147
CHAPTER 4: Formation of the Glycosidic Linkage......Page 156
The different glycosidic linkages......Page 158
Ion pairs and the solvent......Page 159
The 'armed/disarmed' concept......Page 160
The 'torsional control' concept......Page 161
Activation of the glycosyl acceptor......Page 162
'Reciprocal donor/acceptor selectivity'......Page 163
Hemiacetals......Page 164
Glycosyl Esters......Page 167
Glycosyl Halides and Orthoesters......Page 168
The Koenigs–Knorr reaction (1,2-trans)......Page 169
The orthoester procedure (1,2-trans)......Page 171
Halide catalysis (1,2-cis)......Page 173
Glycosyl fluorides (1,2-cis and 1,2-trans)......Page 175
Glycosyl Imidates (1,2-cis and 1,2-trans)......Page 176
Thioglycosides (1,2-cis and 1,2-trans)......Page 179
Seleno- and Telluroglycosides......Page 183
Glycosyl Sulfoxides (sulfinyl glycosides; 1,2-cis and 1,2-trans)......Page 185
Glycals......Page 187
4-Pentenyl Activation (1,2-cis and 1,2-trans)......Page 189
Glycosyl halides......Page 192
Glycosyl sulfoxides (and thioglycosides)......Page 193
β-D-Glucopyranoside to β-D-mannopyranoside......Page 194
Intramolecular aglycon delivery......Page 195
Other methods......Page 196
2-Acetamido-2-deoxy Glycosides......Page 197
2-Deoxy Glycosides......Page 201
Sialosides......Page 203
Furanosides......Page 204
Alkenyl glycosides......Page 205
Remote activation......Page 206
C-Glycosides......Page 209
The addition of carbanions to anomeric electrophiles......Page 210
The addition of electrophiles to anomeric carbanions......Page 211
Glycosyl radicals......Page 213
References......Page 214
Strategies in Oligosaccharide Synthesis......Page 226
Linear syntheses......Page 227
Two-directional syntheses......Page 229
'One-pot' syntheses......Page 230
Polymer-supported Synthesis......Page 233
Types of polymers......Page 234
Linkers......Page 235
Insoluble versus soluble polymers......Page 236
Trichloroacetimidates......Page 237
Glycosyl sulfoxides......Page 238
Glycals......Page 239
Combinatorial synthesis and the generation of 'libraries'......Page 240
References......Page 242
The Role of Charged Intermediates in Basic Metabolism......Page 248
Glucose-6-phosphate: a Central Molecule in Carbohydrate Metabolism......Page 249
Glycolysis......Page 250
Under anaerobic conditions......Page 253
Gluconeogenesis......Page 254
The Pentose Phosphate Pathway......Page 255
The Glyoxylate Cycle......Page 257
Nucleotidylyltransferases......Page 258
Biosynthesis of UDP-glucose, UDP-galactose and galactose......Page 259
Biosynthesis of UDP-glucuronic acid and UDP-xylose......Page 261
Biosynthesis of GDP-mannose......Page 262
Biosynthesis of UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine......Page 263
Biosynthesis of GDP-fucose......Page 265
Biosynthesis of furanosyl nucleoside diphosphates: UDP-galactofuranose and UDP-arabinofuranose......Page 266
Biosynthesis of Sialic Acids and CMP-Sialic Acids......Page 267
Biosynthesis of myo-Inositol......Page 269
Biosynthesis of L-Ascorbic Acid......Page 270
References......Page 272
Glycoside Hydrolases......Page 276
Sequence-based classification of glycoside hydrolases......Page 278
Mechanism of retaining glycoside hydrolases that use carboxylic acids as nucleophiles......Page 279
Mechanism of retaining glycoside hydrolases that use substrate-assisted catalysis......Page 281
Unusual Enzymes that Catalyse Glycoside Cleavage......Page 282
Transglycosidases......Page 285
Structure-based Studies of Glycoside Hydrolases......Page 286
Reagents and Tools for the Study of Glycoside Hydrolases......Page 288
Non-covalent Glycoside Hydrolase Inhibitors......Page 291
Exploitation of Glycoside Hydrolases in Synthesis......Page 295
Kinetic control (transglycosidation)......Page 296
Glycosynthases: Mutant Glycosidases for Glycoside Synthesis......Page 299
Thioglycoligases: Mutant Glycosidases for Thioglycoside Synthesis......Page 301
Hehre Resynthesis/Hydrolysis Mechanism......Page 302
References......Page 303
Classification and Mechanism......Page 308
Mechanism......Page 309
Glycosyltransferases and the 'One-enzyme One-linkage' Hypothesis......Page 314
Sequence-based Classification and Structure......Page 315
Reversibility of Glycosyl Transfer by Glycosyltransferases......Page 316
'Direct' inhibition of glycosyltransferases......Page 317
Therapeutically-useful glycosyltransferase inhibitors......Page 322
'Indirect' inhibition of glycosyltransferases by metabolic interference......Page 324
Chemical Modification of Glycoconjugates Using Metabolic Pathway Promiscuity......Page 326
Use of Glycosyltransferases in Synthesis......Page 328
Enzymatic synthesis using glycosyltransferases and sugar (di)phosphonucleoside donors......Page 329
Multienzyme systems including sugar (di)phosphonucleoside generation and recycling......Page 334
Synthesis using glycosyltransferases in engineered whole cell systems......Page 337
References......Page 339
Cellulose and Cellobiose......Page 344
Starch, Amylopectin, Amylose and Maltose......Page 347
Glycogen......Page 349
Cyclodextrins......Page 350
Sucrose, Sucrose Analogues and Sucrose Oligosaccharides......Page 351
Lactose and Milk Oligosaccharides......Page 354
Fructans......Page 356
Chitin and Chitosan......Page 357
Trehalose and Trehalose Oligosaccharides......Page 358
1,3-β-Glucans......Page 360
Mannans......Page 361
References......Page 362
CHAPTER 10: Modifications of Glycans and Glycoconjugates......Page 366
Epimerization......Page 367
Sulfatases......Page 368
Sulfated glycosaminoglycans......Page 369
Heparin......Page 370
Sulfated carbohydrates from halophilic bacteria......Page 372
Mycobacterial sulfoglycolipids......Page 373
Sulfation in inflammation......Page 374
Sulfatide and seminolipid......Page 375
Mannose-6-phosphate......Page 376
Phosphoglycosylation in Leishmania and other protists......Page 377
Teichoic acids......Page 378
Other phosphoglycans......Page 379
Acylated bacterial antigens......Page 380
Mycobacterial fatty acid esters......Page 382
Carboxylic acid esters in hemicelluloses......Page 383
Modifications of Sialic Acids......Page 385
Other Carbohydrate Modifications......Page 386
References......Page 387
CHAPTER 11: Glycoproteins and Proteoglycans......Page 392
N-Linked Glycosylation......Page 393
Biosynthesis of the lipid-linked oligosaccharide......Page 394
Transfer of the lipid-linked oligosaccharide......Page 395
N-Glycan trimming and the calnexin/calreticulin cycle......Page 396
Golgi processing of N-linked glycans......Page 397
ER-associated protein degradation......Page 398
Diversity of N-linked glycans......Page 399
Inhibitors of N-linked glycoprotein biosynthesis......Page 400
Modification of N-Linked Glycans for Lysosomal Targeting......Page 401
'Mucin-type' O-linked glycosylation......Page 402
The blood group antigens......Page 405
Xenotransplantation and the α-1,3-Gal epitope......Page 409
O-Linked N-Acetyl-β-D-glucosamine......Page 410
Glycosylphosphatidylinositol Membrane Anchors......Page 412
O-Fucose......Page 415
O-Mannose glycans......Page 416
Rare protein modifications......Page 417
Proteoglycans and Glycosaminoglycans......Page 418
Hyaluronan......Page 419
Chondroitin sulfate/dermatan sulfate......Page 420
Keratan sulfate......Page 421
Heparin and heparan sulfate......Page 422
Lysosomal Degradation of Glycoconjugates......Page 425
N-Linked glycoprotein degradation......Page 426
Glycosaminoglycan degradation......Page 427
Treatment of lysosomal storage disorders with imino sugar inhibitors......Page 431
References......Page 433
The Immucillins: Transition-state Analogue Inhibitors of Enzymic N-Ribosyl Transfer Reactions......Page 436
Development of a Candidate Anti-toxic Malarial Vaccine......Page 445
Synthetic Carbohydrate Anti-tumour Vaccines......Page 451
New and Improved Anticoagulant Therapeutics Based on Heparin......Page 458
References......Page 465
Reagents for O-Protecting Group Removal......Page 468
Reagents for N-Protecting Group Removal......Page 469
Reference literature......Page 470
Monographs and related works......Page 471
Recent edited works......Page 472
Recent textbooks......Page 473
Miscellaneous......Page 474
EPILOGUE......Page 476
INDEX......Page 484