Total synthesis and in vivo identification of eicosapentaenoic acid and docosahexanenoic acid-derived Group VI isoprostanes

ORGN 540

Seongjin Kim1, Joshua Rokach1, John A. Lawson2, and Garret A. FitzGerald2. (1) Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology, 150 W. University Blvd., Melbourne, FL 32901, (2) The Center for Experimental Therapeutics, The University of Pennsylvania, Philadelphia, PA 19104

Isoprostanes (iPs), isomeric with prostaglandin, are a new class of natural products. IPs are produced in vivo as a result of free-radical initiated oxygenation of polyunsaturated fatty acids. Using our synthetic standards, we have developed GC/MS and LC/MS methodologies and shown increase urinary levels of the isoprostane formation in disease states such as atherosclerosis and Alzheimer's diseases. Fish oils are the most common dietary sources of w-3 polyunsaturated fatty acid, especially eicosapentaenoic acid (EPA) (20:5 w-3) and docosahexanenoic acid (DHA) (22:6 w-3). The studies about the health related roles for the w-3 fatty acids show the low prevalence of cardiovascular disease in Inuit who eat mostly a fish diet. The total synthesis of group VI isoprostanes derived form EPA and DHA, namely iPF3alpha-VI, iPF4alpha-VI and their tetradeutero derivatives are described. We also report on the first identifications of these iPs in biological fluids.

Bioorganic, Molecular Recognition, Asymmetric Reactions and Syntheses 11:00 AM-1:00 PM, Wednesday, September 10, 2003 Javits Convention Center -- Hall 1B/1C, Poster Division of Organic Chemistry The 226th ACS National Meeting, New York, NY, September 7-11, 2003