Synthesis of new anthracycline derivatives including butyric or retinoic acid moiety

The potential anticancer agents, new anthracycline analogues (2-9) have been synthesized from the glycosides daunomycin (la) and doxorubicin (1b). Compounds 2 and 6 were prepared by nucleophilic displacement esterification of a 14-bromodaunomycin (1c) with sodium or potassium salts of butyric and all trans retinoic acid, respectively. Compounds 3 and 7 were obtained from daunomycin (1a) by direct amidation with a butyric and all trans retinoic acid in the presence of EDCI and PP, respectively. Compounds 4 and 8 were obtained from doxorubicin (1b) by reaction with the corresponding acids in the same manner. Compounds 5 and 9 were prepared from doxorubicin (1b) by acylation with two equivalents of the corresponding acids under the same reaction conditions.