One hundred and eight derivatives of mycophenolic acid (MA) have been prepared by modifications at the phenolic hydroxyl and/or carboxyl sites. None of these compounds was as effective as MA in suppressing cell growth of L-5178Y cell in vitro, whereas several compounds with changes at both the hydroxyl and carboxyl groups were more effective than MA against EHRLICH solid carcinoma and L-1210 leukemia in mice. Mycophenolic acid, a metabolite of Penicillium first isolated in 1896, has been shown by us and other several groups to have antiviral, antitumor, antifungal and immunosuppressive properties. Studies on these activities of MA by our co-workers have been reported in this journal. 1,2,3,4) MA has been reported active against several murine solid tumors and WALKER 256 in rat.2,s,3) This antibiotic is relatively inactive against murine leukemias and ascites tumors but it is active against the ascitic form of the WALKER 256 tumor. Chemical transformation to a product with increased activity against murine leukemia may result in an increase in clinical usefulness of this unique antitumor agent. Previous attempts by others to synthesize more active MA derivatives have not been successful.O,T) We now report several derivatives with increased activities. Materials and Methods Agents Tohoku University, for his critical review of this manuscript.

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