Catalytic asymmetric synthesis: Exploring the reactivity of ketene dimers to access substituted β- lactones as potential fatty acid synthase inhibitors

ORGN 653

Vikram C Purohit, vpurohit@mail.chem.tamu.edu1, Robyn D. Richardson, robynr@burnham.org2, Jeffrey W Smith, jsmith@burnham.org2, and Daniel Romo, romo@mail.chem.tamu.edu3. (1) Department of Chemistry, Texas A&M University, College Station, TX 77843, (2) Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, (3) Department of Chemistry, Texas A & M University, P.O. Box 30012, College Station, TX 77842-3012
Our long standing interest toward the development of new enantioselective methodologies for β - lactone syntheses and their application to the synthesis of complex molecules and natural product analogues, prompted us to explore the reactivity of Calter's ketene dimers as β - lactone precursors. High enantioselectivity realized in the generation of these ketene homo dimers (>95% e.e) has been shown to translate effectively during reducing conditions to deliver cis β - lactones. Furthermore, epimerization of these cis β - lactones provides access to physiologically more useful trans isomers reminiscent of many naturally occurring disubstituted β - lactones. Alkylation and acylation of the cis isomer renders access to β - lactones possessing α quaternary carbon centers in the resulting tri-substituted β - lactones. Some of the results pertaining to this new reactivity of ketene dimers to access functionalized, synthetically and biologically useful β - lactones will be presented.

 

Asymmetric Reactions, Heterocycles, Aromatics, Combinatorial, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 31 August 2005 Washington DC Convention Center -- Hall A, Poster

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005