Chemoenzymatic Synthesis of arabino-Configured Bicyclic Nucleosides

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-a-D-glucofuranose. This synthetic protocol includes some crucial steps such as Vorbruggen base coupling and chemo-enzymatic regioselective acetylation of the primary hydroxyl group by using Lipozyme (R) TL IM where it was found that Lipozyme (R) TL IM could be recovered and reused for selective acetylation without losing its selectivity.

Automated summary

A convergent route has been developed for the synthesis of a new class of bicyclic nucleosides. The synthesis of arabino-configured uracil and thymine bicyclic nucleosides was achieved in 24% and 27% overall yields, respectively, starting from 1,2,5,6-di-O-isopropylidene-α-D-glucofuranose. Important steps in this synthetic protocol include Vorbruggen base coupling and chemo-enzymatic regioselective acetylation using Lipozyme (R) TL IM, which was found to be recoverable and reusable without losing its selectivity.