Stereoselective synthesis and anti-HCV activity of conformationally restricted 2′- C-substituted carbanucleosides

Abstract

Conformationally restricted 2′- C-azido-, hydroxy- and fluoromethyl-carbanucleosides 4b– f were efficiently synthesized via the stereoselective conversion of ketone 7 to epoxide 14, followed by the stereoselective opening of the epoxide with nucleophiles (OAc, N 3, and F), while the corresponding 2′- C-methyl-carbanucleoside 4a was synthesized via the stereoselective Grignard reaction of ketone 7 with methylmagnesium iodide as a key step. All the final nucleosides 4a– f were assayed for anti-HCV activity, but showed neither significant anti-HCV activity nor cytotoxicity in a cell-based replicon assay.