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The new anthracycline analogues (2–10) as potential anticancer agents were synthesized from daunomycin (1a) and doxorubicin (1b). Compounds 2, 6, and 7 were prepared by the nucleophilic displacement type esterification of a 14-bromodaunomycin (1c) with a sodium pyruvate, aspartate, and N-acetylaspartic acid, respectively. Whereas compounds (3, 8) and (4, 9) were prepared by the reaction of daunomycin (1a) or doxorubicin (1b) with one equivalent of the corresponding acids in the presence of EDCI/PP, compounds (5, 10) were obtained from 1b by reaction with two equivalents of the corresponding acids in the same manner.

Department of Chemistry, Woosuk University, Wanju 565-701, KoreaReceived January 30, 2001The potential anticancer agents, new anthracycline analogues ( 2-9) have been synthesized from the glycosidesdaunomycin (1a) and doxorubicin (1b). Compounds 2 and 6 were prepared by nucleophilic displacement es-terification 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 andall trans retinoic acid in the presence of EDCI and PP, respectively. Compounds 4 and 8 were obtained fromdoxorubicin (1b) by reaction with the corresponding acids in the same manner. Compounds 5 and 9 were pre-pared from doxorubicin (1b) by acylation with two equivalents of the corresponding acids under the same re-action conditions.Keywords : Daunomycin, Doxorubicin, Anthracycline derivatives, Butyric and retinoic acid, Acylation.IntroductionThe anthracycline antibiotics daunomycin (1a) and adria-mycin (1b) (Figure 1) are clinically effective anticancerchemotherapeutic agents against several types of humancancers as well as various experimental tumors.

Department of Chemistry, Woosuk University, Wanju 565-701, KoreaReceived March 6, 2001The potential anticancer agents new anthracycline derivatives (2-9) have been synthesized from daunomycin(1a) and doxorubicin (1b) as starting materials. Compounds 2 and 6 were prepared by the nucleophilic dis-placement type esterification of a 14-bromodaunomycin ( 1c) with a acetylsalicylic and palmitic acid in triethyl-amine, respectively. Compounds 3 and 7 were obtained from daunomycin (1a) by direct amidation with thecorresponding acids in the presence of EDCI and PP as esterification reagents. Whereas 4 and 8 were preparedby reaction of doxorubicin (1b) with one equivalent of acetylsalicylic and palmitic acid using DCC/DMAP,respectively, 5 and 9 were obtained from 1b by acylation with two equivalents of the corresponding acids usingEDCI/PP reagents.Keywords : Daunomycin, Doxorubicin, Anthracycline, Acetylsalicyclic acid, Palmitic acid.IntroductionThe substitution of one hydrogen atom in the daunorubicin(daunomycin, DM, 1a) acetyl side chain with a hydroxylgroup gives adriamycin (doxorubicin, DX, 1b) (Figure 1).These anthracycline antibiotics, in particular, are the power-ful antitumor agents in the treatment of a wide range ofhuman cancers.

The new anthracycline analogues (2–10) as potential anticancer agents were synthesized from daunomycin (1a) and doxorubicin (1b). Compounds 2, 6, and 7 were prepared by the nucleophilic displacement type esterification of a 14-bromodaunomycin (1c) with a sodium pyruvate, aspartate, and N-acetylaspartic acid, respectively. Whereas compounds (3, 8) and (4, 9) were prepared by the reaction of daunomycin (1a) or doxorubicin (1b) with one equivalent of the corresponding acids in the presence of EDCI/PP, compounds (5, 10) were obtained from 1b by reaction with two equivalents of the corresponding acids in the same manner.