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‐β‐ 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‐β‐ 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.