Chemo-enzymatic Synthesis of 3′-azido/-amino-C-4′-spirooxetano-xylo nucleosides

Abstract

Conformationally locked 3'-azido-C-4'-spirooxetano-xylonucleosides T, U, C and A have been synthesized by following chemo-enzymatic convergent route. One of the 3'-azido-C-4'- spirooxetano-xylonucleosides, i.e. T was converted into 3'-amino-C-4'-spirooxetano-xylothymidine by reduction of azide to amine with H2/Pd-C in ethyl acetate in quantitative yield. The crucial step in the synthesis of spirooxetano-xylonucleosides is the Lipozyme® TL IM-mediated exclusive diastereoselective acetylation of 4-C-hydroxymethyl group in dihydroxysugar derivative, 3-azido-3-deoxy-4-Chydroxymethyl- 1,2-O-isopropylidene-α-D-xylofuranose in quantitative yield. The diastereoselective monoacetylation of 4-C-hydroxymethyl in dihydroxysugar derivative was unambiguously confirmed by X-ray crystal study on the tosylated compound obtained by the tosylation of Lipozyme® TL IM - mediated monoacetylated sugar derivative. The broader substrate specificity and exclusive selective nature of Lipozyme® TL IM can be utilised for the development of environmentally friendly methodologies for the synthesis of different sugar-modified nucleosides of importance.