Nucleosides. 146. L-methyl-5-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)uracil, The C-nucleoside Isostere of the Potent Antiviral Agent L-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)thymine (fmau). Studies Directed Toward The Synthesis of 2'-deoxy-2'-substituted Arabino Nucleosides. 6

Krzysztof W. Pankiewicz, Barbara Nawrot, Hakan Gadler, Richard W. Price, Kyoichi A. Watanabe

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The synthesis of 5-(2-deoxy-2-fluoro-/3-D-arabinofuranosyl)-l-methyluracil (1, C-FMAU), an isostere of the potent antiviral and antitumor nucleoside 1-(2-deoxy-2-fluoro-/?-D-arabinofuranosyl)thymine (2'-fluoro-5-methyl-ara-U or FMAU), was achieved. Pseudouridine (2) was converted into 4,5'-anhydro-3'-0-acetyl-2'-0-triflylpseudouridine (4), which was treated with tris(dimethylamino)sulfur(l+) difluorotrimethylsilicate (TASF) to give 4,5'-anhydro-5-(3-0-acetyl-2-deoxy-2-fluoro-/3-D-arabinofuranosyl)-l-methyluracil (5b) in 40% yield. Acid hydrolysis of the 4,5'-anhydro linkage of 5b with Dowex 50 (H+) afforded C-FMAU. The inhibitory activity of C-FMAU against HSV-1 and HSV-2 was about 10-fold less than that of FMAU in tissue culture. This compound, however, did not show significant activity in mice inoculated with HSV-1 or HSV-2.

Original languageEnglish (US)
Pages (from-to)2314-2316
Number of pages3
JournalJournal of medicinal chemistry
Volume30
Issue number12
DOIs
StatePublished - Dec 1 1987

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