Stereochemical Assignment of the Protein–Protein Interaction Inhibitor JBIR‐22 by Total Synthesis |
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| Authors: | Alan R. Healy Dr. Miho Izumikawa Prof. Alexandra M. Z. Slawin Dr. Kazuo Shin‐ya Prof. Nicholas J. Westwood |
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| Affiliation: | 1. School of Chemistry and Biomedical Sciences Research Complex, University of St Andrews and EaStCHEM, North Haugh, St Andrews, Fife (UK);2. Japan Biological Informatics Consortium (JBIC) 2‐4‐7 Aomi, Koto‐ku, Tokyo 135‐0064 (Japan);3. National Institute of Advanced Industrial Science and Technology (AIST), 2‐4‐7 Aomi, Koto‐ku, Tokyo 135‐0064 (Japan) |
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| Abstract: | Recent reports have highlighted the biological activity associated with a subfamily of the tetramic acid class of natural products. Despite the fact that members of this subfamily act as protein–protein interaction inhibitors that are of relevance to proteasome assembly, no synthetic work has been reported. This may be due to the fact that this subfamily contains an unnatural 4,4‐disubstitued glutamic acid, the synthesis of which provides a key challenge. A highly stereoselective route to a masked form of this unnatural amino acid now enabled the synthesis of two of the possible diastereomers of JBIR‐22 and allowed the assignment of its relative and absolute stereochemistry. |
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| Keywords: | natural products stereochemistry tetramic acids total synthesis unnatural amino acids |
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