The American Mayapple and its Potential for Podophyllotoxin Production*

INTRODUCTION Podophyllotoxin is the starting material for the semi-synthesis of the anti-cancer drugs etoposide, teniposide and etopophos. These compounds have been used for the treatment of lung and testicular cancers as well as certain leukemias. It is also the precursor to a new derivative CPH 82 that is being tested for rheumatoid arthritis in Europe, and it is the precursor to other derivatives used for the treatment of psoriasis and malaria. Several podophyllotoxin preparations are on the market for dermatological use to treat genital warts. Since the total synthesis of podophyllotoxin is an expensive process, availability of the compound from natural renewable resources is an important issue for pharmaceutical companies that manufacture these drugs. Currently, the commercial source of podophyllotoxin is the rhizomes and roots of Podophyllum emodi Wall. (syn. P. hexandrum Royle), Berberidaceae, an endangered species from the Himalayas. In recent studies, we concluded that the leaf blades of the North American mayapple (P. peltatum L.) may serve as an alternative source of podophyllotoxin production. Since leaves are renewable organs that store lignans as glucopyranosides, podophyllotoxin can be obtained by conversion of podophyllotoxin 4-O-β-D-glucopyranoside into the aglycone using our buffer extraction procedure. This extraction procedure of P. peltatum leaves yields podophyllotoxin in amounts similar to the ethanol extraction of P. emodi rhizomes and roots.