A series of 6-alkyl-6-demethylmitomycins (1-5) was synthesized and eva- luated for anticellular and antitumor activities. These novel compounds were prepared by Michael addition of various carbanion species to 6-de- methyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylidenemitosane (6 and 9) followed by treatment with NH 3 or MeOH/K 2 CO 3 . Alkylation at the C-6 position of 6-demethyl-6-selenide (7) was also useful for the alterna- tive synthesis of 6-alkyl-6-demethylmitomycins. The antitumor activity of these derivatives was evalulated, and 6-demethyl-6-ethylmitomycin A (2a) was found to exhibit excellent activity against S-180 solid tumor in mice. The structure-activity relationship is also discussed