o-Methylation on anthracyclines and anthracyclinones. New o-methyl ethers of daunorubicin and its analogues.
The synthesis of four new ethers of daunorubicin, namely 6-, 9-, 11-monomethyl and 6,9-dimethyl, along with the 4'-methyl ethers of 11-deoxydaunorubicin and 11-deoxydoxorubicin is reported. While the methylation of any of the mentioned hydroxyl groups of the aglycone moiety of daunorubicin resulted in a practically complete loss of bioactivity, the methylation of the aminosugar hydroxyl group of 11-deoxydaunorubicin and 11-deoxydoxorubicin increased their effectiveness on P 388 leukemia in mice.
D000818:Animals; D000903:Antibiotics, Antineoplastic; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D007941:Leukemia P388 / Q000188:drug therapy; D008745:Methylation; D051379:Mice; D009279:Naphthacenes / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; D003630:Daunorubicin