Nucleosides of 1,4-thiazin-3-one and derivatives as tetrahedral intermediate analogs 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-p...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1988-08, Vol.31 (8), p.1575-1579
Main Authors: Marcus, E. Ted, Gundy, Afaf, Levenson, Corey H, Meyer, Rich B
Format: Article
Language:English
Subjects:
Animals
Carbohydrates. Nucleosides and nucleotides
Carbon-Nitrogen Ligases
Chemical Phenomena
Chemistry
Cytidine Deaminase - antagonists & inhibitors
Exact sciences and technology
Humans
Leukemia L1210 - drug therapy
Leukemia, Lymphoid - drug therapy
Ligases - antagonists & inhibitors
Mice
Nucleosides - chemical synthesis
Nucleosides - therapeutic use
Nucleosides, nucleotides and oligonucleotides
Organic chemistry
Preparations and properties
Pyrimidine Nucleosides - metabolism
Structure-Activity Relationship
Thiazines - chemical synthesis
Thiazines - therapeutic use
Tumor Cells, Cultured - drug effects
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00403a015