The Adept Prodrug Cephalosporin Melphalan The Synthesis

ADEPT is a kind of very promising immune treatment for cancer. The method can be add to result of treatment for cancer, and avoiding seriously systemic toxicity. Because of most of anticancer drug have no specificity in cancer chemotherapy, so it may be kill injury normal cells or damage the heart, liver and kidney at the sane time killing tumor cells. As a result, the application dose is limited. It can make cancer treatment to incompletely or vulnerably relapse. Now research shows that tumor tissue is very different in biological characteristics of the surface by normal tissue. Monoclonal antibody can combine with tumor surface antigen, specificity activating enzyme is imported to tumor. Activating enzyme can efficiently provoke active molecules form prodrug releasing, enriching in tumor cells, greatly increasing cancer cure. This is a new kind research of cancer therapy, and also has cancer clinical application.This article discuss how to synthesis C-Mel. To 7-aminocephalosporanic acid as raw materials, getting 3-hydroxymethyl cephalosporin alkyl acid after alkaline hydrolyzing, protecting 7-anmino under alkaline conditions and react of phenyl chloride, protecting 4-bit carboxyl react with diphenyl diazomethane, getting 5 intermediate. Intermediate 5 and 1,2,2,2-tetrac- -hlorodibenzo-ethyl chloro formate to get 3-bit of methylol chloroformate, react with the oxidation give to intermediate 7. Intermediate 7 was condensed with melphalan, after the TFA protecting groups off, getting target compound. Target compounds were synthesized by UV, NMR and mass spectrometry confirmed its structure.