Stereochemical Assignment of the Protein-Protein Interaction Inhibitor JBIR-22 by Total Synthesis

Overview

Journal Angew Chem Weinheim Bergstr Ger

Date 2016 Apr 19

PMID 27087707

Authors

Alan R Healy

Miho Izumikawa

Alexandra M Z Slawin

Kazuo Shin-Ya

Nicholas J Westwood

Affiliations

Soon will be listed here.

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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