The major objective of this project is to develop convergent and flexible routes for the asymmetric total syntheses of the Clerodane and the ent-Clerodane group of diterpene natural products. One of the main differences between the members of the Clerodanes is the placement or absence of oxygen functionality at the various positions of the basic skeleton. The strategy to be employed will hopefully allow access to any one of the members of these natural products by allowing for the selective introduction or removal of oxygen functionality as needed to achieve a specific goal. The Clerodanes and the ent- Clerodanes are a group of diterpenoid natural products which have been found to possess a broad spectrum of biological activity. Some have been shown to be potent insect antifeedants. Others have been found to have antitumor, antimicrobial, antifungal, antiviral, or antiulcer activity. A number of them have been isolated from plants which have been used as medicinal herbs and folk medicines. The synthetic approaches to date have followed conventional methodology for the construction of the bicyclic ring system. Our approach, which utilizes an intramolecular Diels- Alder reaction to construct a tricyclic ring system which can be unraveled to the desired bicyclic skeleton of the Clerodanes, should compliment the routes presently available. Currently, the cycloaddition controls the stereochemistry at three asymmetric centers of the final targets. It is hoped this can be extended to ultimately control the stereochemistry at five contiguous asymmetric centers not only in a relative sense but also in an absolute sense as well.
