SYNTHESIS OF 3'-DEOXY-3'-FLUORO AND 3'-AMINO NUCLEOSIDES FROM 2-METHYLTHIOPYRIMIDIN-4(1H)-ONES

Methyl O-(4-phenylbenzoyl)-beta-D-erythro-pentofuranoside (3) as well as dideoxy-3-phthalimodo-beta-D-erythro-pentofuranose (12) were conden sed with silylated 2-methylthiopyridin-4(1H)-ones 2a, b in the presenc e of trimethylsilyl triflate as a catalyst to produce the correspondin g nucleosides 5, 6, 13. In these reactions, an endocyclic cleavage of C-O in 3 took place; therefore, acyclic nucleosides 4a,b were also for med. All 3'-fluoro nucleosides were deprotected with NH3/MeOH; the 3'- phthalimido nucleosides were deprotected with methylamine in ethanol. The latter method resulted in a concomitant substitution reaction in t he pyrimidine moiety with replacement of the methylthio group. The 2-m ethylthio analogue of 3'-deoxy-3'-fluorothylmidine showed moderate act ivity against HIV-1.