SYNTHESIS OF 2'-AZIDO-2',3'-DIDEHYDRO-2',3'-DIDEOXYTHYMIDINE

Abstract

Compound 15 - the 2'-azido analog of the anti-HIV compound 2',3'-didehydro-2',3'-dideoxythymidine - was synthesized. Treatment of 5'-O-trityl-beta-D-ribofuranosylthymine (1) with DAST or MSTF gave the 2,2'-anhydro derivative 2. The latter and its 3'-O-benzoate 3 were used for the synthesis of the 2'-azido-2'-deoxy derivatives 4 and 5. Two routes to the synthesis of 15 from 5 were investigated. (i) Treatment of 5 with DAST gave a mixture of the 5'-O-trityl derivatives 12 and 13 as well as 1-(2-azido-2,3-dideoxy-3-fluoro-beta-D-xylofuranosyl)thymine (16) along with 2,3'-anhydro derivative 14 (2%). Detritylation of the mixture yielded 15 (39%) and 16 (12%). (ii) Mesylation of 5 gave 17 which yielded 15 upon saponification and detritylation. Compound 15 showed moderate inhibitory activity against HIV-1 and HIV-2 in MT-4 cells.