Chemical modification of hitachimycin. III. Synthesis and antitumor activities of amino acyl derivatives.

Amino acyl derivatives of hitachimycin have been synthesized and evaluated their activities including antibacterial, cytocidal against HeLa cells and in vivo antitumor against sarcoma 180. 15-O-(tert-Butoxycarbonyl(BOC)-glycyl)hitachimycin (2), 15-O-(BOC-beta-alanyl)hitachimycin (4), 15-O-(BOC-(O-tert-Bu)-glutamyl)hitachimycin (6) and 15-O-L-alanylhitachimycin (11) showed comparable in vivo antitumor activity with hitachimycin and the solubility of these compounds was improved.

Chemical modification of hitachimycin. II. Synthesis and antitumor activities of carbonate derivatives.

Several carbonate derivatives of hitachimycin have been synthesized and evaluated their activities including antibacterial, cytocidal against HeLa cells and in vivo antitumor against Sarcoma 180. Some of these derivatives showed higher antitumor activity than hitachimycin. Among the derivatives, 11,15-di-O-methoxycarbonylhitachimycin (2), 11,15-di-O-ethoxycarbonylhitachimycin (3) and 15-O-methoxycarbonylhitachimycin (9) were most effective in in vivo assay.

Chemical modification of hitachimycin. Synthesis, antibacterial, cytocidal and in vivo antitumor activities of hitachimycin derivatives.

Several acyl derivatives of hitachimycin have been synthesized and their activities, including antibacterial, cytocidal against HeLa cells and in vivo antitumor against sarcoma 180, evaluated. Some of these derivatives showed higher antitumor activity than hitachimycin. Among the derivatives, 11-O-propionyl-15-O-butyrylhitachimycin (12) and the 11-O-acylhitachimycins (15-17) were most effective in in vivo assay.

Chemical modification of herbimycin A. Synthesis and in vivo antitumor activities of halogenated and other related derivatives of herbimycin A.

Several halogenated and other related derivatives of herbimycin A have been synthesized and evaluated in vivo for their activities against Ehrlich ascites carcinoma. Some of these derivatives show higher activities than herbimycin A. Among them the derivatives modified at the 4, 5, 6, and 7-positions of the ansa chain showed particularly high activities.