Difluoro-C-glycoside

The replacement of the anomeric oxygen by a CF2 has been considered to obtain hydrolytically stable difluoro-C-glycosides, difluoro-C-disaccharides and difluoro-C-glycopeptides. These compounds have been synthesized [65-68], but their use as inhibitors does not seem to have been biologically validated. 

H. Berber, T. Brigaud, O. Lefebvre, R. Plantier-Royon, C. Portella, Reactions of difluoroenoxysilanes with glycosyl donors Synthesis of difluoro-C-glycosides and difluoro-C-disaccharides, Chem. Eur. J. 7 (2001) 903-909. 

Starting from Difluorovinyl Glycosides Saccharidic derivatives that have a difluoromethylene group in the pseudo-anomeric position are important synthetic intermediates for preparation of difluoro-C-glycosides, difluoro-C-phos-phonates, and difluoro-C-disaccharides. ° ... 

The enolic double bond of a difluorovinyl group in the anomeric position is able to add a radical. It can thus afford a difluoro-C-glycoside, either directly or indirectly. When the alkylating radical is generated from a 6-halogenopyranoside, the reaction can lead to difluoro-C-disaccharide. These reactions are even more efficient if the radical has an electrophilic character (e.g., with an a-halogenoester instead of an alkyl radical). 

Figure 6.26 Synthesis of difluoro-C-glycosides and difluoro-C-disaccharides starting from difiuoroenoxysiianes/ ...

Another promising approach to combining the effect of fluoroalkyl substituent and water solubility was the introduction of a difluoroketone motif as a possible precursor of corresponding acids at C-10. For this purpose we investigated the chemistry of difluoroenoxysilanes, reported as a route to difluoro-C-glycosides [58], Ziffer previously reported that DHA easily reacted with enoxysilanes under Lewis acid catalysis [59],... 

The catalytic hydrogenation of difluorovinylic compounds affords C-difluoro-methyl glycosides and 2-, 3-, or 5-C-difluoromethyl sugars vide supra) (Figure 6.29). In the a-pyranose series, hydrogenation of the exocyclic double bond occurs on the jS... 

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