ASYMMETRIC-SYNTHESIS OF NUCLEOSIDES VIA MOLYBDENUM-CATALYZED ALKYNOL CYCLOISOMERIZATION COUPLED WITH STEREOSELECTIVE GLYCOSYLATIONS OF DEOXYFURANOSE GLYCALS AND 3-AMIDOFURANOST GLYCALS

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 sequ ences featuring asymmetric epoxidations of commercially available ally lic alcohols. The cycloisomerization reaction tvas demonstrated to be compatible with ester and amide functional groups. A 2,3-dideoxyfurano se glycal was stereoselectively converted Into the anti-AIDS beta-nucl eoside stavudine (2',3'-didehydro-2',3'-dideoxythymidine, d4T) and the antiviral 3'-deoxy-beta-nucleoside cordycepin, The anchimeric and hyd rogen-bond-directing effects of 3-amido-2,3-dideoxyfuranose glycals we re exploited in a novel and highly stereoselective synthesis strategy for a variety of biologically active 3'-amino-2',3'-dideoxy- and 3'-am ino-3'-deoxy-beta-nucleosides, including puromycin aminonucleoside, In addition, the mechanism of the molybdenum-catalyzed alkynol cycloisom erization reaction has been studied. Evidence is presented which indic ates that cyclic molybdenum carbene anions are catalytic intermediates in these cyclizations.