PRACTICAL ORGANIC CHEMISTRY: ADVANCED LEVEL
CONTENTS GLYCOCHEMISTRY: OVERVIEW AND PROGRESS 1 1 INTRODUCTION, 1 2 NOMENCLATURE, STRUCTURES, AND PROPERTIES OF SUGARS, 1 2 1 FISCHER PROJECTION, 1 2 2 LINEAR FORMS OF MONOSACCHARIDES, 1 2 3 CYCLIC FORMS OF MONOSACCHARIDES, 1 2 4 HAWORTH AND MILLS PROJECTIONS, 1 2 5 REEVES PROJECTION, 1 2 6 CONFORMATIONAL ANALYSIS, 1 2 7 DISACCHARIDES, OLIGOSACCHARIDES, AND POLYSACCHARIDES, 1 2 8 ANOMERIC EFFECT, 1 2 9 MUTAROTATION, 1 3 HISTORICAL OVERVIEW OF CARBOHYDRATE RESEARCH, 1 3 1 EMIL FISCHER (1852–1919): THE FATHER OF CARBOHYDRATE CHEMISTRY, 1 3 2 KOENIGS–KNORR REACTION, 1 3 3 KARL FREUDENBERG (1886–1983), 1 3 4 BURCKHARDT HELFERICH (1887–1982), 1 3 5 HERMANN FISCHER (1888–1960), CLAUDE HUDSON (1881–1952), HORACE ISBELL (1898–1992), MELVILLE WOLFROM (1900–1969), “SUGAR” RAYMOND LEMIEUX (1920–2000), 1 3 10 ASCENT OF DE NOVO SUGAR SYNTHESIS, 1 4 ONWARD TO THE TWENTY?FIRST CENTURY, GLYCOSYL DONORS AND GLYCOSYLATION SYSTEMS, AUTOMATED AND ONE?POT METHODS FOR OLIGOSACCHARIDE SYNTHESIS, SOLID?PHASE OLIGOSACCHARIDE SYNTHESIS, NATURAL PRODUCT SYNTHESIS, CARBOHYDRATE?BASED THERAPEUTICS, 1 5 CONCLUSION AND OUTLOOK, REFERENCES, 2 PROTECTING GROUP STRATEGIES IN CARBOHYDRATE SYNTHESIS 2 1 INTRODUCTION, 2 2 GENERAL CONSIDERATIONS FOR PROTECTING GROUP SELECTION, RETROSYNTHESIS, NEIGHBORING GROUP PARTICIPATION, INDUCTIVE EFFECT, 2 3 COMMON PROTECTING GROUPS IN CARBOHYDRATE SYNTHESIS, BENZYL ETHERS, ALLYL ETHERS, SILYL ETHERS, ESTERS, AMINE PROTECTING GROUPS, DIOL PROTECTION WITH ACETALS AND KETALS, 2 4 REGIOSELECTIVE PROTECTION OF MONOSACCHARIDES, THROUGH DIFFERENTIATION OF PRIMARY HYDROXYLS USING BULKY PROTECTING GROUPS, THROUGH PROTECTION OF DIOLS WITH ACETALS OR KETALS, 2 5 ONE?POT PROTECTION METHODS, 2 6 CONCLUSION, 3 GENERAL ASPECTS IN O?GLYCOSIDIC BOND FORMATION 3 1 INTRODUCTION, 3 2 SOME BASIC CONCEPTS, MECHANISM OF GLYCOSYLATION, STEREOSELECTIVITY, ANOMERIC EFFECT, PARTICIPATION BY FUNCTIONAL GROUPS IN THE GLYCOSYL DONOR, THE ARMED–DISARMED CONCEPT, ADDITIVES, 3 2 7 SOLVENT EFFECT, 3 2 8 EFFECTS OF OTHER FACTORS ON GLYCOSYLATION, 3 3 METHODS FOR GLYCOSIDIC BOND FORMATION, 3 3 1 GLYCOSYL HALIDES, 3 3 2 GLYCOSYL TRICHLOROACETIMIDATES, 3 3 3 THIOGLYCOSIDES, 3 3 4 N?PENTENYL GLYCOSIDES, 3 3 5 CARBOXYBENZYL GLYCOSIDES, 3 3 6 GLYCOSYL PHOSPHATES/PHOSPHITES, 3 3 7 DEHYDRATIVE GLYCOSYLATION, 3 3 8 GLYCALS, 3 3 9 OTHER GLYCOSYLATION PROTOCOLS, 3 4 GLYCOSYLATION STRATEGIES, 3 4 1 ONE?POT GLYCOSYLATION, 3 4 2 SOLID?PHASE OLIGOSACCHARIDE SYNTHESIS, 3 4 3 CHEMOENZYMATIC GLYCOSYLATION, 3 5 CONCLUSION, 4 CONTROLLING ANOMERIC SELECTIVITY, REACTIVITY, AND REGIOSELECTIVITY IN GLYCOSYLATIONS USING PROTECTING GROUPS 4 1 INTRODUCTION, 4 2 PROTECTING GROUP AND CONTROL OF ANOMERIC SELECTIVITY OF GLYCOSYLATIONS, 4 2 1 NEIGHBORING GROUP PARTICIPATION OF C2 ESTERS TO AFFORD 1,2?TRANS?GLYCOSIDES, 4 2 2 REMOTE NEIGHBORING GROUP PARTICIPATION, 4 2 3 NEIGHBORING GROUP PARTICIPATION BY OTHER FUNCTIONAL GROUPS, 4 2 4 NEIGHBORING GROUP PARTICIPATION USING CHIRAL AUXILIARIES TO OBTAIN 1,2?CIS?GLYCOSIDES, 4 2 5 INTRAMOLECULAR AGLYCONE DELIVERY, 4 2 6 ANOMERIC CONTROL BY ELECTRONIC AND STERIC EFFECTS, 4 2 7 CONFORMATIONAL SELECTION USING A 3,5?O?DI?TERT?BUTYLSILYLIDENE PROTECTING GROUP, 4 2 8 STEREOSELECTIVE INTRODUCTION OF 2?DEOXY?2?AMINOGLYCOSIDES, 4 3 USE OF PROTECTING GROUPS FOR CHEMOSELECTIVE GLYCOSYLATIONS, 4 4 PROTECTING GROUPS IN REGIOSELECTIVE GLYCOSYLATIONS, 4 5 CONCLUSION, 5 STEREOCONTROLLED SYNTHESIS OF SIALOSIDES 5 1 INTRODUCTION, 5 2 CONFORMATIONAL ANALYSIS OF SIALYL OXOCARBENIUM IONS, 5 3 ADDITIVES IN SIALYLATIONS, LEAVING GROUPS IN SIALYLATIONS, INFLUENCE OF THE N5 PROTECTING GROUP ON REACTIVITY AND SELECTIVITY, 4?O,5?N?OXAZOLIDINONE GROUP AND ITS STEREODIRECTING INFLUENCE ON SIALYLATIONS, 4,5?O?CARBONATE PROTECTING GROUP IN ??SELECTIVE KDN DONORS, OTHER CYCLIC AND BICYCLIC PROTECTING SYSTEMS FOR SIALYL DONORS, MECHANISTIC ASPECTS OF SIALYLATION WITH CYCLICALLY PROTECTED SIALYL DONORS, INFLUENCE OF HYDROXY PROTECTING GROUPS ON SIALYL DONOR REACTIVITY AND SELECTIVITY, STEREOSELECTIVE C?SIALOSIDE FORMATION, STEREOSELECTIVE S?SIALOSIDE FORMATION, CONCLUSION, 6 STRATEGIES FOR ONE?POT SYNTHESIS OF OLIGOSACCHARIDES INTRODUCTION, ONE?POT GLYCOSYLATION FROM THE NONREDUCING END TO THE REDUCING END, 6 2 1 REACTIVITY?BASED ONE?POT GLYCOSYLATION: FINE?TUNING OF ANOMERIC REACTIVITIES, 6 2 2 ONE?POT GLYCOSYLATION BASED ON CHEMOSELECTIVE ACTIVATION OF DIFFERENT TYPES OF GLYCOSYL DONORS, 6 2 3 PREACTIVATION?BASED REACTIVITY?INDEPENDENT ONE?POT GLYCOSYLATION, REGIOSELECTIVE ONE?POT GLYCOSYLATION: CONSTRUCTION OF OLIGOSACCHARIDES FROM THE REDUCING END TO THE NONREDUCING END, HYBRID ONE?POT GLYCOSYLATION, ACKNOWLEDGMENTS, 7 AUTOMATED OLIGOSACCHARIDE SYNTHESIS: TECHNIQUES AND APPLICATIONS CHALLENGES AND LIMITATIONS IN SOLUTION?PHASE OLIGOSACCHARIDE SYNTHESIS, 7 3 1 STRATEGIES FOR SOLID?PHASE OLIGOSACCHARIDE SYNTHESIS, AUTOMATED OLIGOSACCHARIDE SYNTHESIS, 7 4 1 TECHNOLOGICAL ASPECTS OF AUTOMATED SOLID?PHASE OLIGOSACCHARIDE SYNTHESIS, 7 4 2 THE FIRST DECADE OF AUTOMATED SYNTHESIS OF OLIGOSACCHARIDES, 7 4 3 RECENT IMPROVEMENTS IN AUTOMATED OLIGOSACCHARIDE SYNTHESIS, 7 4 4 AUTOMATED SYNTHESIS OF CONJUGATION?READY OLIGOSACCHARIDES, 7 4 5 HPLC?ASSISTED AUTOMATED OLIGOSACCHARIDE SYNTHESIS, MICROFLUIDIC TECHNIQUES FOR OLIGOSACCHARIDE SYNTHESIS, CONCLUSION AND OUTLOOK, 8 SUGAR SYNTHESIS BY MICROFLUIDIC TECHNIQUES MICROFLUIDIC GLYCOSYLATION, 8 2 1 MICROFLUIDIC ??SIALYLATION, 8 2 2 GLYCOSYLATION WITH KDO, 8 2 3 STEREOSELECTIVE ??MANNOSYLATION UNDER THE INTEGRATED MICROFLUIDIC AND BATCH CONDITIONS, 8 2 4 CHEMICAL N?GLYCOSYLATION OF ASPARAGINE UNDER THE INTEGRATED MICROFLUIDIC AND BATCH CONDITIONS, 9 CHEMOENZYMATIC SYNTHESIS OF CARBOHYDRATES OLIGOSACCHARIDES AND POLYSACCHARIDES PRODUCED BY GTASES, CHEMOENZYMATIC SYNTHESIS OF HS, 9 3 1 BIOSYNTHETIC PATHWAY OF HS AND HS BIOSYNTHETIC ENZYMES, 9 3 2 APPLICATION OF BIOSYNTHETIC ENZYMES IN HS AND HEPARIN OLIGOSACCHARIDE SYNTHESIS, 9 3 3 STRATEGY FOR CONTROLLED CHEMOENZYMATIC SYNTHESIS, 10 SYNTHESIS OF GLYCOSAMINOGLYCANS 10 1 INTRODUCTION, 10 2 GENERAL STRATEGIES, 10 3 SYNTHESIS OF DERIVATIVES OF L?IDOSE AND IDOA, 10 4 SYNTHESIS VIA STEPWISE SOLUTION?PHASE ASSEMBLY AND COMPOUND DIVERSIFICATION, 10 5 SYNTHESIS VIA SOLUTION?PHASE ONE?POT ASSEMBLY, 10 6 POLYMER?SUPPORTED SYNTHESIS AND AUTOMATION, 10 7 GAG MIMETICS, 10 8 CONCLUSION, 11 CHEMICAL GLYCOPROTEIN SYNTHESIS 11 1 INTRODUCTION, 11 2 OLIGOSACCHARIDE STRUCTURES, 11 3 BIOSYNTHESIS OF GLYCOPROTEINS, 11 4 CHEMICAL PROTEIN SYNTHESIS, 11 4 1 NATIVE CHEMICAL LIGATION, 11 4 2 NCL WITHOUT THE AA?CYS JUNCTION, 11 5 SYNTHESIS OF GLYCOPEPTIDES, 11 6 SYNTHESIS OF GLYCOPEPTIDE??THIOESTERS, 11 6 1 SAFETY?CATCH LINKER, 11 6 2 THIOESTERIFICATION VIA ACTIVATION OF C?TERMINAL CARBOXYLIC ACIDS, 11 6 3 CONVERGENT METHODS FOR THE SYNTHESIS OF GLYCOPEPTIDE??THIOESTERS, 11 6 4 THIOESTERIFICATION VIA O?S TRANSESTERIFICATION FOR THE SYNTHESIS OF GLYCOPEPTIDE??THIOESTERS, 11 6 5 BOC?SPPS FOR THE SYNTHESIS OF SIALYLGLYCOPEPTIDE??THIOESTERS, 11 7 CHEMICAL SYNTHESIS OF GLYCOPROTEINS, 11 7 1 ANTIBACTERIAL GLYCOPROTEIN DIPTERICIN BEARING TWO O?LINKED GALNAC RESIDUES, 11 7 2 LYMPHOTACTIN, 11 7 3 BACTERIAL IMMUNITY PROTEIN IM7, 11 7 4 MUC?2, 11 7 5 GLYCAM?1, 11 7 6 MONOCYTE CHEMOTACTIC PROTEIN?3, 11 7 7 RIBONUCLEASE, 11 7 8 ANTIFREEZE GLYCOPROTEINS, 11 7 9 INTERLEUKIN?8, 11 7 10 INTERFERON???1A, 11 7 11 SAPOSIN C, 11 7 12 ERYTHROPOIETIN, 11 8 CONCLUSION, 12 SYNTHESIS OF GLYCOSPHINGOLIPIDS 12 1 INTRODUCTION, 12 2 CLASSIFICATION AND NOMENCLATURE OF GSLS, 12 3 BIOLOGICAL SIGNIFICANCE OF GSLS, SYNTHESIS OF GSLS, 12 4 1 SYNTHESIS OF GLOBO? AND ISOGLOBO?SERIES GSLS, 12 4 2 SYNTHESIS OF GANGLIOSIDES, 13 SYNTHESIS OF GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORS SYNTHESIS OF THE TRYP BRUCEI GPI ANCHOR, SYNTHESIS OF THE YEAST GPI ANCHOR, SYNTHESIS OF THE RAT BRAIN THY?1 GPI ANCHOR, SYNTHESIS OF PLASMODIUM FALCIPARUM GPI ANCHOR, SYNTHESIS OF TRYPANOSOMA CRUZI GPI ANCHOR, SYNTHESIS OF A HUMAN SPERM CD52 ANTIGEN GPI ANCHOR, SYNTHESIS OF A HUMAN LYMPHOCYTE CD52 ANTIGEN GPI ANCHOR, SYNTHESIS OF THE BRANCHED GPI ANCHOR OF TOXOPLASMA GONDII, 13 10 CONCLUSION, ACKNOWLEDGMENT, 14 SYNTHESIS OF BACTERIAL CELL ENVELOPE COMPONENTS PEPTIDOGLYCAN AND RELATED GLYCOCONJUGATES, 14 2 1 LIPID I, II, AND IV ANALOGUES, 14 2 2 PEPTIDOGLYCAN FRAGMENTS, LPS AND RELATED GLYCOCONJUGATES, 14 3 1 LIPID A, 14 3 2 OLIGO?KDO AND INNER?CORE OLIGOSACCHARIDE, 14 3 3 OUTER?CORE POLYSACCHARIDES, 14 3 4 CAPSULAR POLYSACCHARIDE, 14 3 5 SECONDARY CELL?WALL POLYSACCHARIDE, 14 3 6 ZWITTERIONIC POLYSACCHARIDE, LIPOTEICHOIC ACID, MYCOLYL ARABINOGALACTAN, LAM, AND RELATED GLYCOCONJUGATES, 14 5 1 ARABINAN, GALACTAN, AND RELATED GLYCOCONJUGATES, 14 5 2 MYCOLATES AND RELATED GLYCOCONJUGATES, 14 5 3 LAM AND RELATED GLYCOCONJUGATES, OLIGOSACCHARIDES OF BACTERIAL GLYCOPROTEIN AND RELATED GLYCOCONJUGATES, 14 6 1 O?LINKED OLIGOSACCHARIDE FROM BACILLUS COLLAGEN?LIKE PROTEIN OF ANTHRACIS, 14 6 2 N?LINKED GLYCANS FROM THE GRAM?NEGATIVE BACTERIUM C JEJUNI, 14 7 CONCLUSION, 15 DISCOVERIES AND APPLICATIONS OF GLYCAN ARRAYS 15 1 INTRODUCTION, 15 2 DISCOVERIES OF GLYCAN ARRAYS, 15 2 1 GENERAL, 15 2 2 NONCOVALENT GLYCAN ARRAYS, 15 2 3 COVALENT GLYCAN ARRAYS, 15 2 4 QUALITY CONTROL OF GLYCAN ARRAYS, 15 2 5 DETECTION METHODS OF GLYCAN ARRAYS, 15 3 APPLICATIONS OF GLYCAN ARRAY, 15 3 1 ENZYME ACTIVITY/INHIBITION STUDIES, 15 3 2 GLYCAN ARRAY FOR DISEASES DETECTION AND VACCINE DEVELOPMENT, 15 3 3 CONSORTIUM FOR FUNCTIONAL GLYCOMICS, 15 4 CONCLUSION, 16 SYNTHESIS AND APPLICATIONS OF GLYCONANOPARTICLES, GLYCODENDRIMERS, AND GLYCOCLUSTERS IN BIOLOGICAL SYSTEMS 16 1 INTRODUCTION, 16 2 SIGNIFICANCE OF MULTIVALENT BINDING INTERACTIONS IN BIOLOGICAL SYSTEMS, 16 3 GLYCONANOPARTICLES, GLYCODENDRIMERS, AND GLYCOCLUSTERS: GENERAL OVERVIEW, 16 4 PLANT LECTINS, 16 4 1 CONCANAVALIN A, 16 4 2 PEANUT AGGLUTININ, 16 4 3 WHEAT GERM AGGLUTININ, 16 4 4 RICINUS COMMUNIS AGGLUTININ 120, 16 4 5 OTHER PLANT LECTINS, 16 5 AB5 TOXINS, 16 5 1 CHOLERA TOXIN, 16 5 2 SHIGA?LIKE TOXINS, 16 6 BACTERIAL ADHESION LECTINS, 16 6 1 FIMH ADHESIN, 16 6 2 PA?IL AND PA?IIL, 16 7 INFLUENZA VIRUS, 16 8 DETECTION OF BACTERIA, 16 9 GLYCO?MNPS AS NANOPROBES FOR LABELING CELLS AND MAGNETIC RESONANCE IMAGING AGENTS, 16 10 CYCLOPEPTIDE?BASED GLYCOCLUSTERS AS VACCINE ADJUVANTS, 16 11 CONCLUSION, 17 DESIGN AND SYNTHESIS OF CARBOHYDRATES AND CARBOHYDRATE MIMETICS AS ANTI?INFLUENZA AGENTS 17 1 INTRODUCTION, 17 2 INFLUENZA VIRUSES, 17 2 1 VIRUS MORPHOLOGY, 17 2 2 INFLUENZA A VIRUS EPIDEMIOLOGY, 17 2 3 INFLUENZA A VIRUS LIFE CYCLE, 17 3 DEVELOPMENT OF ANTI?INFLUENZA THERAPEUTICS, 17 4 SIALIC ACID: THE VIRAL CELL?SURFACE RECEPTOR LIGAND, 17 5 HEMAGGLUTININ, 17 6 SIALIDASE, 17 6 1 INFLUENZA VIRUS SIALIDASE ACTIVE SITE, 17 6 2 CATALYTIC MECHANISM OF INFLUENZA VIRUS SIALIDASE, 17 7 INFLUENZA VIRUS SIALIDASE AS A DRUG DISCOVERY TARGET, 17 7 1 STRUCTURE?BASED SIALIDASE INHIBITOR DESIGN ON A SIALIC ACID SCAFFOLD: DEVELOPMENT OF ZANAMIVIR, 17 7 2 SECOND?GENERATION ZANAMIVIR, 17 7 3 SIALIDASE INHIBITORS BASED ON A CYCLOHEXENE SCAFFOLD: DEVELOPMENT OF OSELTAMIVIR, 17 7 4 SIALIDASE INHIBITORS BASED ON FIVE?MEMBERED RING SCAFFOLDS, 17 7 5 SIALIDASE INHIBITORS BASED ON AN AROMATIC RING SCAFFOLD, 17 8 STRUCTURAL DIFFERENCES RECENTLY IDENTIFIED IN INFLUENZA A VIRUS SIALIDASE SUBTYPES, 17 9 NEW INFLUENZA VIRUS SIALIDASE INHIBITORS TARGETING THE 150?CAVITY, 18 DESIGN AND SYNTHESIS OF LIGANDS AND ANTAGONISTS OF SIGLECS AS IMMUNE RESPONSE MODIFIERS 18 1 INTRODUCTION, 18 2 LECTINS, 18 3 SIGLECS, 18 3 1 LIGANDS FOR SIGLECS, 18 3 2 STRUCTURAL FEATURES FOR SIGLEC RECOGNITION, 18 3 3 SIALIC ACID SUBSTRUCTURAL SPECIFICITIES FOR SIGLECS, 18 4 SIGLECS AND INNATE IMMUNITY, 18 4 1 PATHOGEN INTERNALIZATION BY INNATE IMMUNE CELLS: PHAGOCYTOSIS AND ENDOCYTOSIS BY SIGLECS, ATTENUATION OF INFLAMMATORY RESPONSES, IMMUNE EVASION BY PATHOGENS VIA SIGLEC LIGATION, REGULATION OF THE LIFE SPAN OF MYELOID CELLS IN THE CONTEXT OF INFLAMMATION BY SIGLEC?8, SIGLEC?9, AND SIGLEC?F, REGULATION OF NK CELL FUNCTION BY SIGLEC?7, DIRECT ROLE FOR SIGLECS IN T CELLS, SIGLECS IN B?CELL BIOLOGY AND MAINTENANCE OF IMMUNOLOGICAL TOLERANCE, 18 5 DESIGN AND SYNTHESIS OF HIGH?AFFINITY LIGANDS FOR SIGLECS, SIALOADHESIN, CD22, 18 6 CONCLUSION AND FUTURE DIRECTIONS, 19 SUGAR–PROTEIN HYBRIDS FOR BIOMEDICAL APPLICATIONS 19 1 INTRODUCTION, 19 2 CHALLENGES IN THE DEVELOPMENT OF GLYCOPROTEIN?BASED THERAPEUTICS, 19 3 WHY UNNATURAL? 19 4 RETROSYNTHETIC ANALYSIS, 19 5 LINKAGES, THIOETHER, DISULFIDES, AMIDE, AMINE, AMIDINE, UREA AND THIOUREA, DIAZONIUM, TRIAZOLE, OXIME, 19 5 10 CC BOND FORMATION, 19 5 11 ENZYMATIC EXTENSION, 19 6 GLYCOPROTEIN?BASED THERAPEUTICS, CARBOHYDRATE–PROTEIN?BASED (GLYCOCONJUGATE) VACCINES, SYNTHETIC GLYCOPROTEINS AS PATHOGEN?PROCESS INHIBITORS, TARGETED DELIVERY, ENZYME?REPLACEMENT THERAPY, SYNTHETIC GLYCOPROTEINS AS IN VIVO REPORTERS OF DISEASE, 19 7 CONCLUSION,