Synthesis of 3′-Deoxy-3′-fluoro and -3′-amino Nucleosides from 2-Methylthiopyrimidin-4(1H)-ones

Article abstract of DOI:10.1007/BF00807039

Methyl 2,3-dideoxy-3-fluoro-5-O-(4-phenylbenzoyl)-β-D-erythro-pentofuranoside (3) as well as 1,5-di-O-acetyl-2,3-dideoxy-3-phthalimodo-β-D-erythro-pentofuranose (12) were condensed with silylated 2-methylthiopyridin-4(1H)-ones 2a, b in the presence of trimethylsilyl triflate as a catalyst to produce the corresponding nucleosides 5, 6, 13. In these reactions, an endocyclic cleavage of C-O in 3 took place; therefore, acyclic nucleosides 4a, b were also formed. 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 the pyrimidine moiety with replacement of the methylthio group. The 2-methylthio analogue of 3′-deoxy-3′-fluorothylmidine showed moderate activity against HIV-1.