Synthesis and biological studies of 3-(beta-D-ribofuranosyl)-2,3,-dihydro-6H-1,3-oxazine-2,6-dione, a new pyrimidine nucleoside analog related to uridine

J Med Chem. 1976 May;19(5):643-7. doi: 10.1021/jm00227a013.

Abstract

Reaction of the trimethylsilyl derivative of 2,3-dihydro-6H-1,3-oxazine-2,6-dione (2, "uracil anhydride") with protected 1-O-acetylribofuranoses in the presence of stannic chloride gave the corresponding block nucleosides. 3-(2,3-5-Tri-O-2',2',2'-trichloroethoxycarbonyl-beta-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione (4c) thus prepared from the protected sugar 3c, 1-O-acetyl-2,3,5-tri-O-(2,2,2-trichloroethoxycarbonyl)ribofuranose, gave, on removal of the protecting groups with zinc dust,3-(beta-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione (1). The structure of 1 was confirmed by uv, ir, NMR, and CD spectral data and was shown to be an N nucleoside. Uracil anhydride, 2, and, to a lesser extent, its ribonucleoside 1 exert a moderate growth inhibition of mouse leukemia L5178Y, HeLa, and Novikoff hepatoma cells i- culture. Both compounds produce weak inhibition of vaccinia viral replication in HeLa cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / metabolism
  • Cell Line
  • Escherichia coli / drug effects
  • Escherichia coli / growth & development
  • Leukemia L1210 / metabolism
  • Leukemia, Experimental / metabolism
  • Liver Neoplasms / metabolism
  • Mice
  • Neoplasms, Experimental / metabolism
  • Oxazines / chemical synthesis*
  • Oxazines / pharmacology
  • Rats
  • Ribonucleosides / chemical synthesis*
  • Ribonucleosides / pharmacology
  • Uridine / analogs & derivatives*
  • Vaccinia virus / metabolism
  • Virus Replication / drug effects

Substances

  • 3-(beta-D-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione
  • Oxazines
  • Ribonucleosides
  • Uridine