Towards the first asymmetric total synthesis of (-)-Euonyminol

Abstract

(–)-euonyminol is a poly-oxygenated sesquiterpene which was first isolated in 1953 by Beroza. It was isolated by the saponification of a mixture of four alkaloids from Tripterygium wilfordii Hook, a member of the Celastraceae plant family. Since its discovery, (–)-euonyminol has been found to be a common core for a plethora of other Celastraceae natural products. Among these are hypogluanine B and triptonine B, two potent anti-HIV compounds. In this thesis, an overview of the natural products of the Celastraceae is given, highlighting euonyminol as a core of high value both in terms of biological activity and as an intriguing synthetic target. The biological significance of the natural product class is described with particular focus upon anti-HIV and multi-drug resistance reversal properties. Prior synthetic work towards euonyminol and other molecules similar in structure is also described. The remainder of the thesis describes work carried out towards the total asymmetric synthesis of (–)-euonyminol, employing a model system to develop chemistry suitable for installing the southern hemisphere oxygenation pattern. Two synthetic routes are described and both of these feature an Ireland-Claisen rearrangement as the key step.