Synthesis of 1-Methyl-5-(3-azido-2 and 1-Methy1-5-(3-azido-2 The C-Nucleoside Isostere of 3'-Azido-3’-deoxythymidine and Its 2'-“Up”-Fluoro Analogue¹

l-Methyl-5-(3-azido-2,3-dideoxy-jft-D-ery£hro-pentofuranosyl)uracil (C-AZT), a C-nucleoside isostere of the potent anti-AIDS nucleoside 3'-azido-3’-deoxythymidine (AZT), was synthesized. 1 - Methyl- 2^/-deoxy-5^/- O-tri tylpseudouridine (2a) was oxidized with Cr0₃/pyridine/Ac₂0 complex to l-methyl-5-(5-0-trityl-/?-D-£fycero-pentofuranos-3-ulosyl)uracil (12a), which was selectively reduced to l-methyl-5-(5-0-trityl-/3-D-£hreo-pentofuranosyl)uracil (13a). Mesylation of 13a to 14a followed by nucleophilic displacement of the mesyloxy group with azide afforded 3'-azido-2',3'-dideoxy-S'-O-trityl-l-methylpseudoridine (15a), which was detritylated to C-AZT. In a similar manner, 1-methyl-5-(2-deoxy-2-fluoro-£-D-arabinofuranosyl)uracil (C-FMAU, a potent antiherpetic nucleoside) was converted into the 3’-azido analogue (3'-azido-C-FMAU). Both C-AZT and S’-azido-C-FMAU, however, did not exhibit any significant inhibitory activity against HIV in H9 cells.