ANTIVIRAL 1,3-DIOXOLANE NUCLEOSIDES AND SYNTHESIS THEREOF

摘要

A synthesis of 1,3-dioxolane nucleosides that includes condensing a 2-O-protected-5-O-acylated-1,3-dioxolane with a purine or pyrimidine base in the presence of a titanium containing Lewis acid to provide predominately the desired β-isomer in the C1'-position of a 1,3-dioxolane nucleoside. A process for the resolution of a racemic mixture of 1,3-dioxolane nucleoside enantiomers is also disclosed that includes the step of exposing the racemic mixture to an enzyme that preferentially catalyzes a reaction in one of the enantiomers. This invention includes: the compounds (±)-2'-deoxy-5-fluoro-3'-oxacytidine, (-)-2'-deoxy-5-fluoro-3'-oxacytidine, and (+)-2'-deoxy-5-fluoro-3'-oxacytidine; (±)-β-D,L-2'-deoxy-5-fluoro-3'-oxacytidine, its (-) and (+) enantiomers, and pharmaceutically acceptable derivatives and salts thereof for use in medical therapy, for example for the treatment or prophylaxis of an HIV infection; and use of (±)-β-D,L-(±)-β-D,L-2'-deoxy-5-fluoro-3'-oxacytidine, its (-) and (+) enantiomers, and pharmaceutically acceptable derivatives and salts thereof in the manufacture of a medicament for treatment of an HIV infection.