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

Alan R. Healy, Miho Izumikawa, Alexandra M.Z. Slawin, Kazuo Shin-Ya, Nicholas J. Westwood

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)4046-4050
Number of pages5
JournalAngewandte Chemie - International Edition
Volume54
Issue number13
DOIs
StatePublished - Mar 23 2015

Keywords

  • natural products
  • stereochemistry
  • tetramic acids
  • total synthesis
  • unnatural amino acids

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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