Synthesis and conformational analysis of new cyclobutane-fused nucleosides

A stereselective synthesis of 3-oxabicyclo[3.2.0]heptane nucleoside analogues, which were designed as conformational mimics of the anti-HIV agents 2′,3′-didehydro-2′,3′-dideoxythimidine (stavudine, d4T) and 2′,3′-didehydro-2′,3′-dideoxyadenosine (d4A), is described. The target compounds were prepared by condensation of a common intermediate bicyclic acetate, derived from a homochiral 2(5H)-furanone, with pyrimidine and purine bases under modified Vorbrüggen conditions. The conformational behavior of the synthesized nucleoside analogues was studied by NMR spectroscopy and X-ray crystallography. © 2006 American Chemical Society.