Sulfuric Acid Catalyzed Preparation of Alkyl and Alkenyl Camptothecin Ester Derivatives and Antitumor Activity against Human Xenografts Grown in Nude Mice

Camptothecin-20-propinate (CZ48) and other camptothecin ester derivatives were prepared by the esterification reac-tions of camptothecin or 9-nitrocamptothecin with the corresponding acylating agents such as organic acid anhydride or chloride with concentrate sulfuric acid as the catalyst. The sulfuric acid-catalyzed reactions gave high yields of camptothecin ester products.Among the 11 compounds prepared by this method, camptothecin-20-O-propionate, camptothecin-20-O-crotonate, and 9-nitrocamptothecin-20-O-propionate showed good anticancer activity against various types of human tumors grown as xenografts in nude mice. The methodology developed for the preparation of camptothecin esters in this article can be applied to a wide scope of other ester derivatives.