Synthesis of 3′-azido/-amino-xylobicyclonucleosides

Abstract

Lipozyme® TL IM has mediated the selective deacetylation of one of the two diastereotopic acetoxy groups in 4-C-acetoxymethyl-5-O-acetyl-3-azido-3-deoxy-1,2-O-isopropylidene-α-D-xylofuranose, which led to the first efficient synthesis of 3′-azido/3′-amino-xylobicyclonucleosides T, U, C and A from diacetone-D-glucose, in overall yields of 30 to 35%. Single crystal X-ray study on the compound obtained by the tosylation of the lipase-mediated monodeacetylated sugar unambiguously confirmed the point of diastereoselection on the diacetoxy-sugar derivative. The synthesized bicyclic nucleosides have potential application in antisense/aptamer-based oligonucleotide therapeutics development.