Asymmetric Synthesis of Nucleosides via Molybdenum-Catalyzed Alkynol Cycloisomerization Coupled with Stereoselective Glycosylations of Deoxyfuranose Glycals and 3-Amidofuranose Glycals

Abstract

Deoxygenated furanose glycals were efficiently prepared by molybdenum pentacarbonyl-catalyzed cycloisomerization of alkynyl alcohols, which were easily prepared in chiral nonracemic form by short synthetic sequences featuring asymmetric epoxidations of commercially available allylic alcohols. The cycloisomerization reaction was demonstrated to be compatible with ester and amide functional groups. A 2,3-dideoxyfuranose glycal was stereoselectively converted into the anti-AIDS β-nucleoside stavudine (2‘,3‘-didehydro-2‘,3‘-dideoxythymidine, d4T) and the antiviral 3‘-deoxy-β-nucleoside cordycepin. The anchimeric and hydrogen-bond-directing effects of 3-amido-2,3-dideoxyfuranose glycals were exploited in a novel and highly stereoselective synthesis strategy for a variety of biologically active 3‘-amino-2‘,3‘-dideoxy- and 3‘-amino-3‘-deoxy-β-nucleosides, including puromycin aminonucleoside. In addition, the mechanism of the molybdenum-catalyzed alkynol cycloisomerization reaction has been studied. Evidence is presented which indicates that cyclic molybdenum carbene anions are catalytic intermediates in these cyclizations.