Design and synthesis of a novel ring-expanded 4′-thio-apio-nucleoside derivatives

The synthesis of a ring-expanded 4′-thio-apio-nucleoside derivative 4, designed to serve as a potential anti-HIV agent, is described. The epoxy alcohol derivative 10, prepared from 2-butene-1,4-diol, was converted to an allylsulfide derivative 13 in 3 steps. Ring-closing-metathesis of 13 gave the dihydrothiopyran derivative 20, which was further converted into sulphoxide 24. A Pummerer-type thioglycosylation reaction of 24 with a persilylated uracil derivative, followed by conversion to a cytosine derivative and deprotection, gave a racemic mixture of the ring-expanded 4′-thio-apio-nucleoside derivative 4 in good yield.