INGENIOUS ROUTE TO INGENOL

Abstract

INGENOL, A NATURAL PRODUCT isolated from euphorbia plants, has long been a target for synthetic chemists. Not only is it the parent compound of a class of agents with promising bioactivity, but it also has an unusual structural feature that's been extremely difficult to construct synthetically. Various ingenol derivatives have been found to be tumor promoters, antileukemic agents, or inhibitors of human immunodeficiency virus replication. But from the synthetic standpoint, perhaps what has been most intriguing about ingenol is its stereochemistry-a tricky structural arrangement that has provided a difficult synthetic challenge. Several synthetic solutions have been devised to create the trans intrabridgehead framework, but no one had used such an approach in an overall total synthesis of ingenol. Now, chemistry professor Jeffrey D. Winkler and coworkers at the University of Pennsylvania have done just that [ J. Am. Chem. Soc. , 124, 9726 (2002)]. The synthesis-completed by Winkler,...