An alternative strategy for the synthesis of 3′-azido-2′,3′-dideoxy-4′-thionucleosides starting from d-xylose

Methyl 5-O-acetyl-3-azido-2,3-dideoxy-4-thio-α,β-d-erythro-pentofuranoside and 1,5-O-diacetyl-3-azido-2,3-dideoxy-4-thio-α,β-d-erythro-pentofuranose were prepared in twelve and thirteen steps, respectively, by an efficient route starting from d-xylose. Both compounds were easily converted into an anomeric mixture of pyrimidine nucleosides by reaction with the 2,4-bi(trimethylsilyloxy) derivative in the presence of a Lewis acid. The anomeric mixtures were separated by chromatography. The 4′-thio analogue of AZT and related uridine nucleosides have been prepared by a novel and more efficient approach.