Unsaturated fluoroketonucleosides as anticancer agents: the synthesis and biological activity of 5-fluoro-1-(3,4-di-deoxy-3-fluoro-6-O-trityl-beta-d-glycero-hex-3-eno-pyranos-2- ulosyl) uracil.
Direct oxidation of 5-fluoro-1-(4-O-acetyl-3-deoxy-3-fluoro-6-O-trityl-beta-D-glucopyranosyl) uracil 9 led to the title compound 10 after a beta-elimination reaction. The formation of the hydrate of ketone 10 due to the highly electronegative fluorine atom in the a position to the carbonyl group, prompted us to carry out a comparative study of different methods of oxidation and to define the best strategy for the synthesis of such molecules. Results of in vitro and in vivo biological evaluations are reported.
Ecole Nationale Supzrieure de Chimie, CNRS-UMR 7001, Paris, France.
M J
MJ
Egron
B I
BI
Dorange
K
K
Antonakis
J
J
Herscovici
A P
AP
Ollapally
D000818:Animals; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D009005:Monosaccharides / Q000138:chemical synthesis* / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C120718:5-fluoro-1-(3,4-dideoxy-3-fluoro-6-O-trityl-glycero-hex-3-eno-pyranos-2-ulosyl); D009005:Monosaccharides; D009705:Nucleosides; D005472:Fluorouracil