Synthesis and antitumor activity of 5'-demethyl-5'-trifluoromethyl-daunorubicin and -doxorubicin.
The title compounds were prepared by coupling phenyl 4-O-acetyl-2,3,6-trideoxy-6,6,6-trifluoro-1-thio-3-trifluoroacetamido -alpha-L- and beta-L-lyxo-hexopyranoside with daunomycinone. The key step of this synthesis is the C-trifluoromethylation of a 1-protected 2,3-dideoxy-3-azido-D-erythro-pentodialdose, prepared from 2-deoxy-D-erythro-pentose, to give a 6,6,6-trifluoro-L-lyxo-hexose derivative. The synthetic products showed higher cytotoxicity than doxorubicin against most of the human tumor cell lines tested in vitro, possibly by the effect of the CF3 group at C-5'.
Nakai
K
K
Institute of Bioorganic Chemistry, Kawasaki, Japan.
Takagi
Y
Y
Ogawa
S
S
Tsuchiya
T
T
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity*; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C400078:7-O-(3-amino-2,3,6-trideoxy--6,6,6-trifluoro-lyxo-hexopyranosyl)adriamycinone; C400077:7-O-(3-amino-2,3,6-trideoxy-6,6,6-trifluoro-lyxo-hexopyranosyl)daunomycinone; D000970:Antineoplastic Agents; D004317:Doxorubicin; D003630:Daunorubicin