Nucleosides of 1,4-thiazin-3-one and derivatives as tetrahedral intermediate analogues of enzymes in pyrimidine nucleoside metabolism.
Reaction of the trimethylsilylated derivative of 1,4-thiazin-3-one with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of SnCl4 gave, after deblocking, 4-beta-ribofuranosyl-1,4-thiazin-3-one (8). Treatment of 1,4-thiazin-3-one with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofuranose in the presence of sodium hydride provided, after deblocking, the corresponding 2-deoxy-beta-D-ribofuranosyl derivatives (19). Oxidation of 4-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-1,4-thiazin-3-one (7) with 1 equiv of m-chloroperbenzoic acid resulted in 4-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-1,4-thiazine-2,3-dione (9) and 4-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-1,4-thiazin-3-one 1-oxide (10). Evidence is presented that indicates that the oxidation of the thiazine at the 2-position is due to a Pummerere rearrangement. The new compounds failed to show significant activity against tumor cell lines in culture, L1210 cells in vivo, virus cytotoxicity in cell culture, or cytidine deaminase.
Marcus
T E
TE
College of Pharmacy, Washington State University, Pullman 99164.
Gundy
A
A
Levenson
C H
CH
Meyer
R B
RB
D000818:Animals; D019731:Carbon-Nitrogen Ligases; D055598:Chemical Phenomena; D002621:Chemistry; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D008025:Ligases / Q000037:antagonists & inhibitors*; D051379:Mice; D009705:Nucleosides / Q000138:chemical synthesis* / Q000627:therapeutic use; D011741:Pyrimidine Nucleosides / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects
D009705:Nucleosides; D011741:Pyrimidine Nucleosides; D013843:Thiazines; D003564:Cytidine Deaminase; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase