Date of Award
Doctor of Philosophy
The 12,13-epoxytrichothecenes exhibit a variety of biological activities. Several compounds are of particular interest because they are among the most potent cytostatic agents yet discovered. As a result of their biological activities and novel structures, the epoxytrichothecenes have been the objects of intense synthetic activity;A program was undertaken to develop a synthetic route to the AB ring system of the trichothecenes. After initial approaches employing intramolecular etherifications failed, the cis-fused system was successfully produced via a Diels-Adler reaction of methyl coumalate and isoprene;Seeking an improved route, studies were made of intramolecular cyclizations involving allylic carbonium ions. Initial successes in model systems could not be extended to suitably functionalized systems. Ultimately, an efficient seven-step sequence was developed for the production of the AB ring system. The key reaction of this route was the reduction of an acetal to an ether;The course of this research led to the development of two novel synthetic methods: preparation of allylic alcohols from epoxides using iodotrimethylsilane, and selective reductions via enolate protection. The conversion of epoxides of allylic alcohols was found to proceed regiospecifically with trisubstituted epoxides. This procedure compliments previously developed methods. The use of enolate anions as protecting groups served as a convenient procedure for selective reductions of various functionalities employing a variety of reducing agents.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/
Kevin Alan Frazier
Frazier, Kevin Alan, "Synthetic approaches toward 12,13-epoxytrichothecenes " (1981). Retrospective Theses and Dissertations. 7167.