First synthesis of diethyl N-acetyl-glycosamine-1-difluoromethylphosphonate from 2-nitroglycals as phosphate analog

• Diastereoselective Michael addition of TMSCF2P(O)(OEt)2 onto 2-nitroglycals.
• Replacement of an oxygen by the difluoromethylene group to mimic the anomeric linkage.
• First access to N-acetyl-glycosamine-1-difluorophosphonate, as potent glycomimetics.

Herein, we report the first access to diethyl glycosamine-1-difluoromethylphosphate as phosphate mimic. The diethyl 2-nitro-glycosides-β-1-difluoromethylphosphonate were obtained from a Michael addition of diethyl(difluoro-(trimethylsilyl)methyl)phosphonate on 2-nitroglycals in the presence of a fluoride promoter in good to excellent yields. A subsequent reduction of the nitro group leads to the N-acetyl glycosides derivative giving a straightforward access to phosphate analogs.

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