Index
I
Chapter 1. Synthesis and regio- and stereochemical behavior in nucleophilic addition reactions of carba-glycal derived vinyl epoxides
1
1.1. Introduction 1
1.2. State of the art 1
1.3. Synthesis of racemic epoxides 1.17α and 1.17β 6
1.4. Addition reactions of O-nucleophiles to epoxides 1.17α and 1.17β 8 1.5. Methanolysis of epoxides 1.17α and 1.17β in the presence of an ionic liquid 14
1.6. Experimental 17
Chapter 2. Carbaglycal-derived vinyl N-nosyl aziridines as useful tools to access aminocyclitols
21
2.1. Introduction 21
2.2. Aminocyclitols in nature 21
2.3. Aminocyclohexytols as glycohydrolase inibitors 22
2.4. Synthesis of vinyl aziridines 1.18α-Ns and 1.18β-Ns 23 2.5. Regio- and stereoselective behavior of N-nosyl aziridines 1.18α-Ns and
1.18β-Ns in nucleophilic addition reactions of O-nucleophiles
27
2.6. Regio- and stereoselective behavior of N-nosyl aziridines 1.18α-Ns and 1.18β-Ns in nucleophilic addition reactions of N-Nucleophiles
31
2.7. Experimental 33
Chapter 3. Stereodivergent synthesis of enantiomerically pure diastereoisomeric carba analogs of glycal-derived vinyl epoxides and corresponding N-acetyl aziridines: a new access to carbasugars
45
3.1. Sterodivergent synthesis of vinyl epoxides (-)-1.17α and (-)-1.17β 45 3.2. Synthesis of N-acetyl aziridines (-)-1.18α-Ac and (-)-1.18β-Ac 53
3.3. Experimental 56
Chapter 4. Functionalization of the double bond of the carbaglycals 69
4.1. Introduction 69
4.2. Functionalization of 1,2-double bond in racemic carbaglucal systems 70 4.3. Functionalization of the double bond in 1,2-addition products from N-nosyl
aziridines 1.18α-Ns and 1.18β-Ns
80
4.4. Experimental 85
Index
II
Chapter 5. DC-SIGN, a C-type lectine on dendritic cell (DC) involved in several pathogen infections
95
5.1. Introduction 95
5.2. Carbohydrate chemistry applied to the synthesis of DC-SIGN ligand 97
5.3. Synthesis of pseudomannobiosides 5.6 and 5.7 98
5.4. Synthesis of 4’-N-nosyl pseudomannobiosides 5.21a and 5.21b 107
5.5. Experimental 109
Chapter 6. Regio- and stereoselective behavior of L -arabinal-derived vinyl epoxide 6.1 in nucleophilic addition reactions
125
6.1. Synthesis of the
L-arabinal-derived vinyl epoxide 6.1 125
6.2. Reaction of epoxide 6.1 with O-Nucleophiles 127
6.3. Reactions of epoxide 6.1 with C-Nucleophiles 131
6.4. Reaction of epoxide 6.1 with N-Nucleophiles 132
6.5. Reaction of epoxide 6.1 with S-Nucleophiles 135
6.6. Conclusions 135
6.7. Experimental 136
Chapter 7. Synthesis of enantiomerically pure cis-2,5-disubstituted-2,5- dihydropyrroles
151
7.1. Introduction 151
7.2. Reactions of vinyl aziridines 1.2α-Ms and 1.2β-Ms 153
7.3. Experimetal 162
Chapter 8. Synthesis of glycoconjugates and pseudoglycoconjugates as a potential antitumor agents
171
8.1. Introduction 171
8.2. Tumor hypoxia 171
8.3. Cancer associated metabolic alterations 172
8.4. The glycolytic process 172
8.5. Structure and function of human lactate dehydrogenase 174
8.6. Catalytic mechanism of hLDH 175
8.7. Human LDH isoform 5 as anticancer target 176
8.8. Inhibitors of hLDH 177
8.9. N-hydroxyindole-derived compounds as LDH5 inhibitors 177
8.10. General structural requirements 178
8.11. Synthesis of β-gulo and α-mannoglycoconjugates 181
Index
III
8.12. Synthesis of carba 1,2-epoxides 190
8.13. Enzymatic and cellular assays of glycoconjugates and carbaglycoconjugate 200
8.13.1. Enzyme inhibition
200
8.13.2. Cell-based reduction of lactate production
201
8.13.3. In vitro effects on cell proliferation
