BIOTRANSFORMATION OF DIBENZYLBUTANOLIDES BY PEROXIDASE ENZYMES - ROUTES TO THE PODOPHYLLOTOXIN FAMILY

In continuing studies on enzyme-catalyzed cyclization of synthetic dib enzylbutanolides to members of the podophyllotoxin family, experiments which involve the biotransformation of such synthetic substrates with horseradish peroxidase and with enzymes produced by the cell culture of Nicotiana sylvestris are presented. Cyclization of synthetic 3 to t he desired 5 proceeds efficiently with purified horseradish peroxidase enzyme but not with the acetone powder. A much preferred route to 5, in gram scale synthesis, involves the biotransformation of 3 with the enzymes produced by the cell culture of Nicotiana sylvestris. This sta ble cell line; when grown in bioreactors, produces sufficient quantiti es of enzyme for efficient multi-gram synthesis in short time incubati ons (5-30 min). The application of this methodology for production of podophyllotoxins utilized as starting materials in etoposide synthesis is under study in our laboratory.