Total synthesis of salinosporamide and derivatives by an intramolecular nucleophile-catalyzed process

ORGN 852

Gil Ma1, Henry Nguyen1, Seongho Oh2, and Daniel Romo1. (1) Department of Chemistry, Texas A&M University, P.O. Box 30012, College station, TX 77842-3012, (2) Department of Chemistry, Johns Hopkins University, 3400N Charles street, Baltimore, MD 21218
Omuralide (1) and salinosporamide A (2) are unique structures possessing a lactam fused ß-lactone that have attracted attention from both synthetic and biological perspectives. We previously developed a catalytic, asymmetric intramolecular nucleophile-catalyzed aldol-lactonization (NCAL) process that allows access to optically pure carbocycle-fused ß-lactones from aldehyde-acid substrate (JACS, 2001, 123, 7945). We recently extended this process to the use of keto-acid substrates greatly expanding the scope of this process. Returning to one of our initial inspirations for the development of the NCAL process, we have now applied this transform to the lactam fused ß-lactone core structures found in salinosporamide (2) and the Bayer compound (3). The synthesis of these natural products and implications for a possible biosynthetic pathway will be described.

 

Total Synthesis of Complex Molecules
8:00 AM-12:00 PM, Thursday, 14 September 2006 Moscone Center -- Room 134, Oral

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006