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-α-l- and β-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′.