Efficient syntheses of alpha- and beta-C-nucleosides and the origin of anomeric selectivity

Abstract

C-Nucleosides constitute a valuable class of compounds in biological and medicinal chemistry studies. We report herein a new and efficient synthesis of both alpha- and beta-C-nucleosides with high anomeric selectivity from N⁶-Boc protected purine analogues. The synthetic approach features a carefully designed lithiation and silane reduction sequence. The anomeric stereochemistry outcome is dictated by the protecting group of sugar lactones. Computational studies suggest that previously neglected interactions between partially positively-charged silane and the substitutions on a sugar moiety play important roles in the anomeric selectivity of silane-mediated C-nucleoside synthesis.