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Stereochemical Assignment of the Protein–Protein Interaction Inhibitor JBIR‐22 by Total Synthesis
Author(s) -
Healy Alan R.,
Izumikawa Miho,
Slawin Alexandra M. Z.,
Shinya Kazuo,
Westwood Nicholas J.
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201411141
Subject(s) - subfamily , diastereomer , stereochemistry , chemistry , stereoselectivity , amino acid , total synthesis , biochemistry , combinatorial chemistry , gene , catalysis
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.