ORGN 239 |
| Salinosporamide A (NPI-0052; 1) is a potent inhibitor of the 20S proteasome that is currently in clinical trials for the treatment of cancer. Structure 1 is a densely functionalized small molecule with 5 contiguous chiral centers which makes it an extremely attractive and challenging synthetic target. We have developed a novel enantioselective total synthesis of (-)-1 through a key intermediate, oxazolidine-g-lactam 3. This intermediate was synthesized from D-serine-derived b-keto amide (2) by enantioselective intramolecular aldol cyclization which generated 3 contiguous chiral centers. The synthesis of (-)-1 from 3 involves Brown's allylboration chemistry to install the cyclohexene ring and inversion of C-5 center by oxidation followed by enzymatic reduction. Details of this total synthesis and analogue preparation from this method will be presented.
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Total Synthesis, Materials, Devices and Switches, Molecular Recognition and Self-Assembly, Biologically-Related Molecules and Processes
8:00 PM-10:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Sci-Mix
Division of Organic Chemistry |
