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

Elzbieta Sochacka, Barbara Nawrot, Krzysztof W. Pankiewic2z, Kyoichi A. Watanabe

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1995-1999
Number of pages5
JournalJournal of Medicinal Chemistry
Volume33
Issue number7
DOIs
StatePublished - Jan 1 1990

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