Preparation of Highly Substituted Cyclohexene Systems

University Of California-Los Angeles, Los Angeles CA

Investigators

Abstract

This project is focused on the development of cycloaddition processes that allow the rapid and efficient preparation of very hindered cyclohexene systems in high yields with excellent diastereoselectivity. The use of a strong Lewis acid (AlBr3) in the presence of a weak Lewis acid (AlMe3), in which AlMe3 acts as an acid scavenger, allows acid-labile functional groups to be used efficiently. The simple formation and novel formal [3,3]-sigmatropic rearrangement of the [2+2] cycloadducts of allenecarboxylates and silyloxy dienes permits the construction of very hindered cyclohexenes, e.g., those with two contiguous quaternary centers, in only two or three steps. The new methodology will be applied to the syntheses of four biologically active natural products, the cardiotonic agent ouabain, the antitumor compound haterumaimide E, and the anti-inflammatory diterpenes hedychilactone B and hedychenone. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Michael E. Jung, of the Department of Chemistry and Biochemistry at the University of California - Los Angeles. Many complex natural products contain polysubstituted six-membered rings as an integral part of their structure, demanding the development of new methods for their synthesis. Professor Jung and his students are studying novel and efficient reaction sequences allowing the construction of complex organic structures with precise control over three-dimensional structures. Complex organic structures often play critical roles in the development of new drugs or new materials that will be increasingly important as technological developments in molecular medicine and nanotechnology increase.