Synthesis of 3′-C-Phosphono Nucleosides from α,β-Unsaturated Lactone

Abstract

The reaction of 5-protected α,β-unsaturated γ-lactone 4 with trialkylphosphite gave 3′-C-dialkylphosphono-erythro lactone 5 in high yields. The lactone 5 was reduced with DIBAL to the corresponding lactol, which was converted to the acetate 6 by treatment with acetic anhydride in pyridine. The acetate 6 was coupled with silylated thymine in the presence of TMS-triflate and the resulting anomeric mixture of nucleotides could be separated chromatographically and after desilylation using TBAF in THF the 3′-C-dialkylphosphono nucleosides 7 and 8 were obtained.