Adriamycin analogs. 2. Synthesis of 13-deoxyanthracyclines

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Abstract
The syntheses of several 13-deoxyanthracyclines are described. Koenigs-Knorr condensation of .epsilon.-rhodomycinone (12) with the protected daunosaminyl chloride afforded the glycoside 14 after deprotection. Efforts to decarbomethoxylate 12, and attempts to selectively deoxygenate the 13 position of daunomycinone and adriamycinone, were unsuccessful as approaches to 13-deoxyanthracyclines. Reaction of the readily available tosylhydrazones 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 efficacy and potency in the P-388 mouse leukemia screen. The .epsilon.-rhodomycinone glycoside 14 was less active than 6 and 7.