Progress toward the asymmetric synthesis of ( - )-gephyrotoxin

by (Teresa Marie), 1972- Miller

Miller, Teresa M.: Progress Toward the Asymmetric Synthesis of (-)-Gephyrotoxin. (Under the direction of Dr. Daniel L. Comins) This research has focused on the asymmetric synthesis of the natural product (-)gephyrotoxin. This product was isolated and characterized by Daly and coworkers in 1977. Kishi and co-workers published the first synthesis of (-)-gephyrotoxin in 1980, and the first synthesis of (+)-gephyrotoxin in 1981. No synthesis of (-)-gephyrotoxin has been published to date. In exploring the possibilities for the synthesis of (-)-gephyrotoxin, many synthetic transformations were investigated including, Horner-Wadsworth-Emmons, Diels-Alder, orthoester Claisen, and Mukaiyama-Michael addition. Diels-Alder and Horner- Wadsworth-Emmons Chemistry was explored for formation of the 6,6 trans ring system necessary for (-)-gephyrotoxin. Previously synthesis of only cis ring systems had been developed. Orthoester Claisen rearrangement and Mukaiyama-Michael addition were investigated to set the C6 and 5a stereocenters. Our progress toward the synthesis of (-)-gephyrotoxin yielded other developments as well. The formation of both the cis and trans 4-hydroxy -3,4-dihydro-2H-pyridines was accomplished for the first time, and the formation of 5-iodo, and 5-vinyl-2,3-dihydro-4pyridones was improved. Progress Toward the Asymmetric Synthesis of (-)-Gephyrotoxin By Teresa M. Miller A dissertation submitted to the Graduate Faculty of North Carolina State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy Department of Chemistry Raleigh, North Carolina 2004 Approved by: ___________________________________ Dr. Daniel L. Comins, Chair ___________________________________ Dr. Jonathan Lindsey ___________________________________ _______________________________ Dr. Suzanne T. Purrington Dr. Carl Bumgardner