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.
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.
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002460:Cell Line; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D007939:Leukemia L1210 / Q000378:metabolism; D007942:Leukemia, Experimental / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism; D010078:Oxazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D014529:Uridine / Q000031:analogs & derivatives*; D014616:Vaccinia virus / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
C012534:3-(beta-D-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione; D010078:Oxazines; D012263:Ribonucleosides; D014529:Uridine