Studies towards the total synthesis of CP-225,917 and CP-263,114

Abstract

This thesis describes advanced model studies directed to the synthesis of CP- 225,917 and CP-263,114, complex natural products that have been shown to inhibit enzymes that are involved in cholesterol biosynthesis and in the development of many cancers. A route was devised to the functionalized pentacyclic skeleton of these natural products. The most advanced intermediate carries the essential substituents for construction of the anhydride subunit and one of the two olefinic arms that are present in both compounds. The approach used involves a Diels- Alder reaction, an unusual fragmentation of a strained [2.2.1]bicycle and the method of intramolecular conjugate displacement, which had previously been developed in this laboratory. A number of model studies were carried out to identify a procedure for introducing the last carbon required for the anhydride subunit and, based on these studies, that carbon was introduced via the use of a [2,3]-Wittig rearrangement.