Synthesis of Podophyllotoxin Derivatives

Podophyllotoxin is a natural aryltetralin lignan compound isolated from plants within the genus Podophyllum. Podophyllotoxin has been under extensive biochemical investigation since the discovery of its biological activity as a strong microtubule destabilizing mitotic agent. Although these antineoplastic compounds have shown significant activity as cancerous cell growth inhibitors, they lack selectivity and are thus extremely toxic to healthy cells. This has led to a recent interest in the synthesis of Podophyllotoxin analogues in hopes of optimizing the biological selectivity and potency of these semi-synthetic derivatives. The objective of my research in the Roche group is to generate a library of these derivatives for subsequent biological assays to determine their potential as chemotherapeutic agents. In total I have synthesized 22 Podophyllotoxin analogues. Of these 22 derivatives, 14 have been biologically evaluated and 4 were observed to possess promising anti-cancer activity and are currently undergoing further evaluation.