Multicopper Clusters Enable Oxidative Phenol Macrocyclization (OxPM) of Peptides

Anna Libman, Mor Ben-Lulu, Eden Gaster, Ratnadeep Bera, Alexander I. Shames, Omer Shaashua, Vlada Vershinin, Yury Torubaev, Doron Pappo

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The biosynthesis of glycopeptide antibiotics such as vancomycin and other biologically active biaryl-bridged and diaryl ether-linked macrocyclic peptides includes key enzymatic oxidative phenol macrocyclization(s) of linear precursors. However, a simple and step-economical biomimetic version of this transformation remains underdeveloped. Here, we report highly efficient conditions for preparing biaryl-bridged and diaryl ether-linked macrocyclic peptides based on multicopper(II) clusters. The selective syntheses of ring models of vancomycin and the arylomycin cyclic core illustrate the potential of this technology to facilitate the assembly of complex antibiotic macrocyclic peptides, whose syntheses are considered highly challenging. The unprecedented ability of multicopper(II) clusters to chelate tethered diphenols and promote intramolecular over intermolecular coupling reactions demonstrates that copper clusters can catalyze redox transformations that cannot be accessed by smaller metal catalysts.

Original languageEnglish
Pages (from-to)21002-21011
Number of pages10
JournalJournal of the American Chemical Society
Volume145
Issue number38
DOIs
StatePublished - 27 Sep 2023

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry

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