Multicopper Clusters Enable Oxidative Phenol Macrocyclization (OxPM) of Peptides.

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.

Mechanistic Insights into the FeCl-Catalyzed Oxidative Cross-Coupling of Phenols with 2-Aminonaphthalenes.

The selective FeCl-catalyzed oxidative cross-coupling reaction between phenols and primary, secondary, and tertiary 2-aminonaphthalene derivatives was investigated. The generality of this scalable method provides a sustainable alternative for preparing ,-biaryl compounds that are widely used as ligands and catalysts. Based on a comprehensive kinetic investigation, a catalytic cycle involving a ternary complex that binds to both the coupling partners and the oxidant during the key oxidative coupling step is postulated.

Synthesis of Biaryl-Bridged Cyclic Peptides via Catalytic Oxidative Cross-Coupling Reactions.

Biaryl-bridged cyclic peptides comprise an intriguing class of structurally diverse natural products with significant biological activity. Especially noteworthy are the antibiotics arylomycin and its synthetic analogue G0775, which exhibits potent activity against Gram-negative bacteria. Herein, we present a simple, flexible, and reliable strategy based on activating-group-assisted catalytic oxidative coupling for assembling biaryl-bridged cyclic peptides from natural amino acids.