Carbohydrates (eBook)

Front Cover 1
Carbohydrates: The Essential Molecules of Life 4
Copyright Page 5
Table of Contents 8
Preface and Acknowledgements 18
Abbreviations 20
CHAPTER 1: The 'Nuts and Bolts' of Carbohydrates 24
The Early Years 24
The Constitution of Glucose and Other Sugars 30
The Cyclic Forms of Sugars, and Mutarotation 38
The Shape (Conformation) of Cyclic Sugars, and the Anomeric Effect 46
References 55
CHAPTER 2: Synthesis and Protecting Groups 58
Esters 59
Acetates 59
Benzoates 61
Chloroacetates 62
Pivalates 62
Levulinates 62
Carbonates, borates, phosphates, sulfates and nitrates 63
Sulfonates 64
Ethers 65
Methyl ethers 65
Benzyl ethers 66
4-Methoxybenzyl ethers 67
Allyl ethers 68
Trityl ethers 68
Silyl ethers 68
Acetals 70
Cyclic acetals 72
Benzylidene acetals 73
4-Methoxybenzylidene acetals 76
Isopropylidene acetals 77
Diacetals 80
Cyclohexylidene acetals 81
Dithioacetals 81
Thioacetals 81
Stannylene acetals 82
The Protection of Amines 84
Orthogonality 89
References 90
CHAPTER 3: The Reactions of Monosaccharides 98
Oxidation 98
Reduction 103
Halogenation 107
Non-anomeric halogenation 108
Anomeric halogenation 112
Alkenes and Carbocycles 116
Non-anomeric alkenes 116
Anomeric alkenes 117
Carbocycles 119
Anhydro Sugars 121
Non-anomeric anhydro sugars 122
Anomeric anhydro sugars 124
Deoxy, Amino Deoxy and Branched-chain Sugars 128
Deoxy sugars 128
Amino deoxy sugars 130
Branched-chain sugars 134
Miscellaneous Reactions 135
Wittig reaction 135
Thiazole-based homologation 136
Mitsunobu reaction 137
Orthoesters 138
Industrially Important Ketoses 140
D-Fructose 140
L-Sorbose 142
Isomaltulose 142
Lactulose 143
Aza and Imino Sugars 144
References 147
CHAPTER 4: Formation of the Glycosidic Linkage 156
General 158
The different glycosidic linkages 158
The mechanism of glycosidation 159
Ion pairs and the solvent 159
The substituent at C2 160
The 'armed/disarmed' concept 160
The 'torsional control' concept 161
The 'latent/active' concept 162
Activation of the glycosyl acceptor 162
The concept of 'orthogonality' 163
'Reciprocal donor/acceptor selectivity' 163
Hemiacetals 164
Glycosyl Esters 167
Glycosyl Halides and Orthoesters 168
The Koenigs–Knorr reaction (1,2-trans) 169
The orthoester procedure (1,2-trans) 171
Halide catalysis (1,2-cis) 173
Glycosyl fluorides (1,2-cis and 1,2-trans) 175
Glycosyl Imidates (1,2-cis and 1,2-trans) 176
Thioglycosides (1,2-cis and 1,2-trans) 179
Seleno- and Telluroglycosides 183
Glycosyl Sulfoxides (sulfinyl glycosides 1,2-cis and 1,2-trans)
Glycals 187
4-Pentenyl Activation (1,2-cis and 1,2-trans) 189
ß-D-Mannopyranosides (1,2-cis) 192
Glycosyl halides 192
Glycosyl sulfoxides (and thioglycosides) 193
ß-D-Glucopyranoside to ß-D-mannopyranoside 194
Intramolecular aglycon delivery 195
Other methods 196
ß-Rhamnopyranosides (1,2-cis) 197
2-Acetamido-2-deoxy Glycosides 197
2-Deoxy Glycosides 201
Sialosides 203
Furanosides 204
Miscellaneous Methods 205
Alkenyl glycosides 205
Remote activation 206
C-Glycosides 209
The addition of carbanions to anomeric electrophiles 210
The addition of electrophiles to anomeric carbanions 211
Glycosyl radicals 213
Miscellaneous 214
References 214
CHAPTER 5: Oligosaccharide Synthesis 226
Strategies in Oligosaccharide Synthesis 226
Linear syntheses 227
Convergent syntheses 229
Two-directional syntheses 229
'One-pot' syntheses 230
Polymer-supported Synthesis 233
Types of polymers 234
Linkers 235
Attachment of the sugar to the linker/polymer 236
The glycosyl donors used 236
Insoluble versus soluble polymers 236
Trichloroacetimidates 237
Pentenyl glycosides 238
Glycosyl sulfoxides 238
Thioglycosides 239
Glycals 239
Automated oligosaccharide synthesis 240
Combinatorial synthesis and the generation of 'libraries' 240
References 242
CHAPTER 6: Monosaccharide Metabolism 248
The Role of Charged Intermediates in Basic Metabolism 248
Glucose-6-phosphate: a Central Molecule in Carbohydrate Metabolism 249
Glycolysis 250
The Fate of Pyruvate in Primary Metabolism 253
Under aerobic conditions 253
Under anaerobic conditions 253
Gluconeogenesis 254
The Pentose Phosphate Pathway 255
The Glyoxylate Cycle 257
Biosynthesis of Sugar Nucleoside Diphosphates 258
Nucleotidylyltransferases 258
Biosynthesis of UDP-glucose, UDP-galactose and galactose 259
Biosynthesis of UDP-glucuronic acid and UDP-xylose 261
Biosynthesis of GDP-mannose 262
Biosynthesis of UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine 263
Biosynthesis of UDP-N-acetylmuramic acid 265
Biosynthesis of GDP-fucose 265
Biosynthesis of furanosyl nucleoside diphosphates: UDP-galactofuranose and UDP-arabinofuranose 266
Biosynthesis of Sialic Acids and CMP-Sialic Acids 267
Biosynthesis of myo-Inositol 269
Biosynthesis of L-Ascorbic Acid 270
References 272
CHAPTER 7: Enzymatic Cleavage of Glycosides: Mechanism, Inhibition and Synthetic Applications 276
Glycoside Hydrolases 276
Retaining and Inverting Mechanisms 278
Sequence-based classification of glycoside hydrolases 278
Mechanism of inverting glycoside hydrolases 279
Mechanism of retaining glycoside hydrolases that use carboxylic acids as nucleophiles 279
Mechanism of retaining glycoside hydrolases that use tyrosine as a catalytic nucleophile 281
Mechanism of retaining glycoside hydrolases that use substrate-assisted catalysis 281
Unusual Enzymes that Catalyse Glycoside Cleavage 282
Transglycosidases 285
Structure-based Studies of Glycoside Hydrolases 286
Reagents and Tools for the Study of Glycoside Hydrolases 288
Non-covalent Glycoside Hydrolase Inhibitors 291
Exploitation of Glycoside Hydrolases in Synthesis 295
Thermodynamic control (reversed hydrolysis) 296
Kinetic control (transglycosidation) 296
Glycosynthases: Mutant Glycosidases for Glycoside Synthesis 299
Thioglycoligases: Mutant Glycosidases for Thioglycoside Synthesis 301
Hehre Resynthesis/Hydrolysis Mechanism 302
References 303
CHAPTER 8: Glycosyltransferases 308
Classification and Mechanism 308
Classification 309
Mechanism 309
Glycosyltransferases and the 'One-enzyme One-linkage' Hypothesis 314
Sequence-based Classification and Structure 315
Reversibility of Glycosyl Transfer by Glycosyltransferases 316
Inhibitors of Glycosyltransferases 317
'Direct' inhibition of glycosyltransferases 317
Therapeutically-useful glycosyltransferase inhibitors 322
'Indirect' inhibition of glycosyltransferases by metabolic interference 324
Chemical Modification of Glycoconjugates Using Metabolic Pathway Promiscuity 326
Use of Glycosyltransferases in Synthesis 328
Enzymatic synthesis using glycosyltransferases and sugar (di)phosphonucleoside donors 329
Multienzyme systems including sugar (di)phosphonucleoside generation and recycling 334
Synthesis using glycosyltransferases in engineered whole cell systems 337
References 339
CHAPTER 9: Disaccharides, Oligosaccharides and Polysaccharides 344
Cellulose and Cellobiose 344
Starch, Amylopectin, Amylose and Maltose 347
Glycogen 349
Cyclodextrins 350
Sucrose, Sucrose Analogues and Sucrose Oligosaccharides 351
Lactose and Milk Oligosaccharides 354
Fructans 356
Chitin and Chitosan 357
Trehalose and Trehalose Oligosaccharides 358
1,3-ß-Glucans 360
Mannans 361
References 362
CHAPTER 10: Modifications of Glycans and Glycoconjugates 366
Epimerization 367
Sulfation 368
Sulfotransferases 368
Sulfatases 368
Sulfated glycosaminoglycans 369
Heparin 370
Nodulation factors 372
Sulfated carbohydrates from halophilic bacteria 372
Mycobacterial sulfoglycolipids 373
Sulfated nucleosides 374
Sulfation in inflammation 374
Sulfatide and seminolipid 375
Phosphorylation 376
Mannose-6-phosphate 376
Phosphoglycosylation in Leishmania and other protists 377
Teichoic acids 378
Other phosphoglycans 379
Carboxylic Acid Esters 380
Acylated bacterial antigens 380
Mycobacterial fatty acid esters 382
Carboxylic acid esters in hemicelluloses 383
Modifications of Sialic Acids 385
Other Carbohydrate Modifications 386
References 387
CHAPTER 11: Glycoproteins and Proteoglycans 392
N-Linked Glycosylation 393
Biosynthesis of the lipid-linked oligosaccharide 394
Transfer of the lipid-linked oligosaccharide 395
N-Glycan trimming and the calnexin/calreticulin cycle 396
Golgi processing of N-linked glycans 397
ER-associated protein degradation 398
Diversity of N-linked glycans 399
Inhibitors of N-linked glycoprotein biosynthesis 400
Modification of N-Linked Glycans for Lysosomal Targeting 401
O-Linked Mucins/Proteoglycans, Blood Group Antigens and Xenorejection 402
'Mucin-type' O-linked glycosylation 402
The blood group antigens 405
Xenotransplantation and the a-1,3-Gal epitope 409
O-Linked N-Acetyl-ß-D-glucosamine 410
Glycosylphosphatidylinositol Membrane Anchors 412
Other Types of Protein Glycosylation 415
O-Fucose 415
C-Mannose 416
O-Mannose glycans 416
Rare protein modifications 417
Proteoglycans and Glycosaminoglycans 418
Hyaluronan 419
Chondroitin sulfate/dermatan sulfate 420
Keratan sulfate 421
Heparin and heparan sulfate 422
Lysosomal Degradation of Glycoconjugates 425
N-Linked glycoprotein degradation 426
Glycosaminoglycan degradation 427
Treatment of lysosomal storage disorders with imino sugar inhibitors 431
References 433
CHAPTER 12: Classics in Carbohydrate Chemistry and Glycobiology 436
The Immucillins: Transition-state Analogue Inhibitors of Enzymic N-Ribosyl Transfer Reactions 436
Development of a Candidate Anti-toxic Malarial Vaccine 445
Synthetic Carbohydrate Anti-tumour Vaccines 451
New and Improved Anticoagulant Therapeutics Based on Heparin 458
References 465
APPENDIX I 468
Reagents for O-Protecting Group Removal 468
Reagents for N-Protecting Group Removal 469
APPENDIX II 470
Carbohydrate Nomenclature 470
The Literature of Carbohydrates 470
Reference literature 470
Primary literature 471
Monographs and related works 471
Recent edited works 472
Recent textbooks 473
Miscellaneous 474
EPILOGUE 476
INDEX 484