Chemoenzymatic Synthesis of arabino-Configured Bicyclic Nucleosides

Abstract

A convergent route for the synthesis of a new class of bicyclic nucleosides has been developed. The synthetic route to the corresponding arabino-configured uracil and thymine bicyclic nucleosides proceeds in 24 and 27% overall yields, respectively, starting from 1,2,5,6-di-O-isopropylidene-α-d-glucofuranose. This synthetic protocol includes some crucial steps such as Vorbrüggen base coupling and chemo-enzymatic regioselective acetylation of the primary hydroxyl group by using Lipozyme® TL IM where it was found that Lipozyme® TL IM could be recovered and reused for selective acetylation without losing its selectivity.