Total Synthesis of TMC-95A and -B via a New Reaction Leading to Z-Enamides. Some Preliminary Findings as to SAR
- 27 April 2004
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 126 (20) , 6347-6355
- https://doi.org/10.1021/ja049821k
Abstract
A full account of the total syntheses of proteasome inhibitors TMC-95A and -B is provided. A key feature of the syntheses involved installation of a cis-propenylamide moiety by a thermal rearrangement of an α-silylallyl amide. The scope and mechanism of the enamide-forming reaction are discussed. Also provided are some preliminary results from SAR studies. It was found that simplified analogues can retain the full potency of proteasome inhibition.Keywords
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