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Stereochemical assignment of the protein-protein interaction inhibitor JBIR-22 by total synthesis.

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.

SUBMITTER: Healy AR

PROVIDER: S-EPMC4441253 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Stereochemical assignment of the protein-protein interaction inhibitor JBIR-22 by total synthesis.

Healy Alan R AR Izumikawa Miho M Slawin Alexandra M Z AM Shin-Ya Kazuo K Westwood Nicholas J NJ

Angewandte Chemie (International ed. in English) 20150204 13

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 mask ...[more]

PMID: 25650886

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