A versatile stereocontrolled synthesis of 2-deoxyiminosugar C-glycosides and their evaluation as glycosidase inhibitors

Abstract

Dihydroxylation of (R,S) or (S,S)-2,6-disubstituted dehydropiperidines enantioselectively obtained from stannylated precursors allows a versatile preparation of 2-deoxyiminosugar C-glycosides which have been evaluated as glycosidases inhibitors.

Epoxide‐Mediated Trans‐Thioglycosylation and Application to the Synthesis of Oligosaccharides Related to the Capsular Polysaccharides of C. jejuni HS:4

“…It is well‐known that the glycosidic linkages in carbohydrate immunogens are susceptible to in vivo degradation by glycoside hydrolases, thus using antigenic carbohydrate analogs that are more resistant to enzymatic hydrolysis [15–20] have been considered as a viable strategy, as using stable synthetic analogs of such classes would ensure the integrity of the carbohydrate antigens during immunization thus the raised antibodies are more consistent to the structures of intact antigens. Two exemplary approaches have been reported by replacing the glycosidic oxygen(s) of the native carbohydrate antigens with a sulfur or carbon atom to generate the corresponding enzyme‐resistant S ‐glycosides [21–28] or C ‐glycosides [29–33] . For S ‐glycosides, studies have shown that although the C−S single bond is longer than the C−O bond, the C−S−C bond angle is significantly smaller than the C−O−C angle, which often results in very little differences between the position of the carbon atoms of the two types of glycosidic linkages; [34–40] studies have also shown that while S ‐glycosides are more flexible about the glycosidic linkage, they do sample similar conformational space of their O ‐glycoside counterparts.…”

“…Two exemplary approaches have been reported by replacing the glycosidic oxygen(s) of the native carbohydrate antigens with a sulfur or carbon atom to generate the corresponding enzyme-resistant S-glycosides [21][22][23][24][25][26][27][28] or C-glycosides. [29][30][31][32][33] For S-glycosides, studies have shown that although the CÀ S single bond is longer than the CÀ O bond, the CÀ SÀ C bond angle is significantly smaller than the CÀ OÀ C angle, which often results in very little differences between the position of the carbon atoms of the two types of glycosidic linkages; [34][35][36][37][38][39][40] studies have also shown that while S-glycosides are more flexible about the glycosidic linkage, they do sample similar conformational space of their O-glycoside counterparts. Thus geometrically, S-glycosides can effectively mimic their native O-glycosides when used as an antigen.…”

Stereoselective Synthesis of Nojirimycin α-C-Glycosides from a Bicyclic Acyliminium Intermediate: A Convenient Entry to N,C-Biantennary Glycomimetics

“…The intrinsic instability of aminoacetal functionalities makes impractical the synthesis of iminosugar O -glycosides or of analogues having other heteroatom substituents at the pseudoanomeric position. Instead, aglycon-like appendages have been incorporated through N -substitution − and C -branching approaches, − which accounts for the two major subclasses of iminosugar derivatives on record.…”