A process for preparation of anticancer drug 9-nitro camptothecin

摘要

Camptothecin and some of its semisythetic derivatives such as topotecan, irinotecan and 9-nitrocamptothecin, have exhibited strong antitumor activity against various experimental tumor model. The water insoluble 9-nitrocamptothecin demonstrated very potent antitumor activity against many different types of human cancers and HIV. Literature procedures for preparing 9-nitrocamptothecin are direct nitration of camptothecin using a concentrated nitric/concentrated sulfuric acid system or a combination of two or more different nitrate salts/concentrated sulfuric acid system. The two systems demand on the chromatographically separation, which is a hindrance to industrial production. We found that the main products of nitration of camptothecin,9-nitrocamptothecin and 12-nitrocamptothecin, have the great difference for the solubility in the organic solvent. So we studied various organic solvent for the crude product obtained from nitration of camptothecin using KNO3/concentrated sulfuric acid system. At last we found that the ethyl acetate is the best solvent for extraction of the reaction solution and tchloroform and the ether is the best solvent for recrystalization by screening various polarity of organic solvent.