Synthesis and antitumor activity of 7-O-[2,6-dideoxy-2-fluoro-5-C-(trifluoromethyl)-alpha-L-talopyranosyl]- daunomycinone and -adriamycinone.
7-O-[2,6-Dideoxy-2-fluoro-5-C-(trifluoromethyl)-alpha-L-talopyranosyl]- daunomycinone and -adriamycinone have been prepared by the coupling of 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-5-C-(trifluoromethyl)-alpha-L- talopyranosyl iodide with daunomycinone. The key steps in this synthesis are the regioselective fluorination of methyl alpha-D-lyxopyranoside to give the 4-deoxy-4-fluoro-beta-L-ribopyranoside and the C-trifluoromethylation of the aldehydo-L-ribose derivative to give the 1,1,1-trifluoro-5-monofluoro-L-altritol derivative. Antitumor activities of the synthetic products were compared with those for the 2'-deoxy-2'-fluoro and 2',6'-dideoxy-5'-C-trifluoromethyl analogs.
Institute of Bioorganic Chemistry, Kawasaki, Japan.
K
K
Nakai
Y
Y
Takagi
T
T
Tsuchiya
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship
C121461:7-O-(2,6-dideoxy-2-fluoro--5-C-(trifluoromethyl)talopyranosyl)adriamycinone; C121460:7-O-(2,6-dideoxy-2-fluoro-5-C-(trifluoromethyl)talopyranosyl)daunomycinone; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D003630:Daunorubicin