Adriamycin analogues. 2. Synthesis of 13-deoxyanthracyclines.
The syntheses of several 13-deoxyanthracyclines are described. Koenigs-Knorr condensation of epsilon-rhodomycinone (12) with the protected daunosaminyl chloride 15 afforded 14 after deprotection. Efforts to decarbomethoxylate 12, as well as attempts to selectively deoxygenate the 13 position of daunomycinone and adriamycinone, were unsuccessful as approaches to 13-deoxyanthracyclines. However, reaction of the readily available tosylhydrazones 4 and 5, of daunorubicin and adriamycin with NaCNBH3 in acidic MeOH, afforded the 13-deoxy analogues 6 and 7 in satisfactory yield. These compounds retained antitumor activity, being comparable to the parent compounds in both efficacy and potency in the P-388 mouse leukemia screen. The epsilon-rhodomycinone glycoside 14 was less active than 6 and 7.
D000818:Animals; D004247:DNA / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D007942:Leukemia, Experimental / Q000188:drug therapy*; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D051379:Mice
D004317:Doxorubicin; D004247:DNA; D003630:Daunorubicin