[Potential antileukemic agents, synthesis of derivatives of indirubin, indigo, and isoindigotin].

Indirubin is used clinically for the treatment of chronic granulocytic leukemic in China. Our previous paper reported the syntheses of N_1′substituted derivatives of indirubin. In an attempt to study the role of N_1-substitution and connecting position of two indole rings in the antitumor activity, two N_1-substituted and one N_1N_1, -bissubstituted derivatives of indirubin (Ⅰ_1, Ⅰ_2, Ⅰ_3), and six bisindolinones, derivatives of indigo and isoindigotin (Ⅱ_(1～3), Ⅲ_(1～3)) were synthesized. In the. preparation of compounds Ⅰ_(1～3) from N-alkyl-O-acetyl indoxyl Ⅳ (R=-CH_3 or -C_2H_5) with isatin or N-methylisatin, the self-condensation of the indoxyl to N-substituted indigo is suppressed by using strong acid, p-toluenesulfonic acid as condensing catalyst. It has been suggested that aminium formation stabilizes the indoxyl compound thus inhibits the self-condensation and facilitates the desired condensation of indoxyl with isatin to give a yield of 60%. Treatment of indigo with equimolecular quantity of sodium hydride, followed by corresponding alkyl halides, gave compounds Ⅱ_(1～3). Isoindigotin series compunds Ⅲ_(1～3) were obtained by condensation of the oxindole with corresponding N-alkylisatin. The lipid soluble N-ethyl indigo and N-methyl or N-ethyl isoindigotin exhibit inhibitory action on Walker carcinoma 256 against which their parent compounds are inactive. Substitution on N_1-position of indirubin caused loss of activity, but N_1N_1, -dimethylindirubin (Ⅰ_3) exhibits certain anticancer activity.