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