Synthetic studies of nucleoside antibiotics: a formal synthesis of (+)-sinefungin.

Abstract

A formal synthesis of (+)-sinefungin 1 is described. The C-6′ and C-9′ stereogenic centers of sinefungin were constructed stereoselectively by efficient catalytic asymmetric syntheses. The key strategy for the construction of the C-6′ stereocenter involves alkylation of a protected ribose-derived triflate with alkynyl-lithium, Sharpless asymmetric epoxidation of the corresponding allylic alcohol followed by a regioselective epoxide-ring opening with diisopropoxytitanium diazide. The C-9 amino acid stereochemistry was established by a rhodium chiral bisphosphine-catalyzed asymmetric hydrogenation of an α-(acylamino)acrylate derivative. The resulting amino acid derivative has been previously converted to (+)-sinefungin 1.