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. An efficient route to a set of pyrimidine nucleosides fused with a 4′-C,3′-O-propylene bridge has been developed. Antiviral and cytotoxicity activities of these bicyclic nucleosides, as well as their phosphoramidate prodrugs, are presented. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.