title: Nucleosides. 146. 1-Methyl-5-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil, the C-nucleoside isostere of the potent antiviral agent 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (FMAU). Studies directed toward the synthesis of 2'-deoxy-2'-substituted arabino nucleosides. 6.
abstract: The synthesis of 5-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1-methyluracil (1, C-FMAU), an isostere of the potent antiviral and antitumor nucleoside 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (2'-fluoro-5-methyl-ara-U or FMAU), was achieved. Pseudouridine (2) was converted into 4,5'-anhydro-3'-O-acetyl-2'-O-triflylpseudouridine (4), which was treated with tris(dimethylamino)sulfur (1+) difluorotrimethylsilicate (TASF) to give 4,5'-anhydro-5-(3-O-acetyl-2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1- 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.
authors.affiliation: Laboratory of Organic Chemistry, Sloan-Kettering Institute for Cancer Research, New York, New York.
authors.forename: K W
authors.initials: KW
authors.lastname: Pankiewicz
authors.forename: B
authors.initials: B
authors.lastname: Nawrot
authors.forename: H
authors.initials: H
authors.lastname: Gadler
authors.forename: R W
authors.initials: RW
authors.lastname: Price
authors.forename: K A
authors.initials: KA
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018139:Simplexvirus / Q000187:drug effects; D014529:Uridine / Q000031:analogs & derivatives*
chemical_list: D000998:Antiviral Agents; C054364:1-methyl-5-(2-deoxy-2-fluoroarabinofuranosyl)uracil; D001086:Arabinofuranosyluracil; C034935:clevudine; D014529:Uridine