Method for the synthesis of 2',3′-dideoxy-2′,3′-didehydronucleosides

Abstract

An efficient synthetic route to antiviral 2',3′-dideoxy-2′,3′-didehydro-nucleosides, such as 2′,3′-dideoxy and 2′- or 3′-deoxyribo-nucleoside analogs, from available precursors is disclosed, with the option of introducing functionality as needed. In one embodiment, a method for the preparation of β-D and β-L-2′,3′-dideoxy-2′,3′-didehydro-nucleosides is described that includes: activating a compound of structure (1)wherein B is a pyrimidine or purine base and Y is O, S or CHwith an acyl halide of the formula X—C(═O)R, X—C(═O)C(R)OC(═O)Ror X—C(═O)OR(wherein X is a halogen, and each Ris independently hydrogen, lower alkyl, alkyl, aryl or phenyl); reducing the resulting compound with a reducing agent to form a 2′,3′-dideoxy-2′,3′-didehydro-nucleoside; and optionally deprotecting the nucleoside. The haloacylation of the first step can form the 2′-acyl-3′-halonucleoside, the 3′-acyl-2′-halonucleoside, or a mixture thereof.