Application of a directed Sm(II)-mediated cyclization in an approach to pestalotiopsin A

ORGN 420

David J. Edmonds, Christopher J. O'Brien, and David J. Procter. Department of Chemistry, University of Glasgow, University Avenue, Glasgow, G12 8QQ, United Kingdom
Approaches to the total synthesis of the sesquiterpene pestalotiopsin A are described. The key step in the approach involves a stereodirected SmI2-mediated ketyl-olefin cyclization to form a cyclobutanol intermediate. The stereoselective synthesis of an enantiopure cyclization substrate is described. A remote stereogenic centre in this substrate controls facial selectivity in the SmI2-mediated cyclization. The crucial role of the co-solvent 2,2,2-trifluoroethanol in the cyclization is discussed

Manipulation of the cyclobutanol product has resulted in the first synthesis of the bicyclic core of the natural product. A variety of approaches to the nine-membered carbocycle of the target are possible via elaboration of the protected core.

 

Total Synthesis, Asymmetric Reactions and Syntheses, Bioorganic
9:00 AM-11:00 AM, Wednesday, March 31, 2004 Anaheim Convention Center -- Hall C, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, March 29, 2004 Anaheim Convention Center -- Hall A, Sci-Mix

Division of Organic Chemistry

The 227th ACS National Meeting, Anaheim, CA, March 28-April 1, 2004