Nonenolizable podophyllotoxin derivatives

To block epimerization and the resulting biological deactivation podophyllotoxin compounds, the lactone carbonyl group has been changed to methylene. Syntheses of several of these delactonized derivatives are described, all with modifications in the original lactone ring and some without the 4-hydroxyl group. Several biological assays show that most of the nonenolizable derivatives retain activity.