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

Alan Healy, Miho Izumikawa, Alexandra Martha Zoya Slawin, Kazuo Shin-ya, Nicholas James Westwood

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)
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Abstract

Recent reports have highlighted the biological activity associated with a sub-family of the tetramic acid class of natural products. Despite the fact that members of this sub-family act as protein-protein interaction inhibitors of relevance to proteasome assembly, no synthetic work has been reported. This may be because this sub-family contains an unnatural 4,4-disubstitued glutamic acid, the synthesis of which provides a key challenge. Here we describe a highly stereoselective route to a masked form of this unnatural amino acid. This enabled the synthesis of two of the possible diastereomers of JBIR-22 and allowed its relative and absolute stereochemistry to be assigned.
Original languageEnglish
Pages (from-to)4046-4050
JournalAngewandte Chemie
Volume54
Issue number13
Early online date4 Feb 2015
DOIs
Publication statusPublished - 23 Mar 2015

Keywords

  • Natural products
  • Stereochemistry
  • Tetramic acids
  • Total synthesis
  • Unnatural amino acids

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