Biocatalytic route to C-4′-spiro-oxetano-xylofuranosyl pyrimidine nucleosides

Abstract

A facile access to C-4′-spiro-oxetano-xylofuranosyl nucleosides has been demonstrated for the first time through Lipozyme® TL IM-mediated regioselective acetylation of one of the primary hydroxyl group over the other primary and secondary hydroxyl groups in 3′-O-benzyl-4′-C-hydroxymethyl-β-D-xylofuranosyl nucleosides. Attempts to optimize a convergent route for these spironucleosides via selective manipulation of hydroxyl groups in 3-O-benzyl-4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-xylofuranose were unsuccessful. Nevertheless; the present linear biocatalytic route efficiently afforded the C-4′-spiro-oxetanoxylofuranosyl nucleosides T and U in 47 and 38% overall yields, respectively, starting from corresponding furanose diol.