Synthesis and Biological Evaluation of 4′-C,3′-O-Propylene-Linked Bicyclic Nucleosides

A set of pyrimidine nucleosides fused with a 4′-C,3′-O-propylene bridge was successfully synthesised in 12 steps from 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose, an inexpensive starting material, based on a ring-closing metathesis (RCM) reaction followed by Vorbrüggen-type nucleobase coupling. Antiviral and cytotoxicity activities of the targeted modified nucleosides, as well as their phosphoramidate prodrugs, are described.