Synthesis of Fluorescent Cyclic Peptides via Gold(I)-Catalyzed Macrocyclization
Xingyu Liu, Wei Cai, Nathan Ronceray, Aleksandra Rađenović, Beat Fierz, Jérôme Waser
Abstract
High Resolution Image Download MS PowerPoint Slide Rapid and efficient cyclization methods that form structurally novel peptidic macrocycles are of high importance for medicinal chemistry. Herein, we report the first gold(I)-catalyzed macrocyclization of peptide-EBXs (ethynylbenziodoxolones) via C 2 -Trp C–H activation. This reaction was carried out in the presence of protecting group free peptide sequences and is enabled by a simple commercial gold catalyst (AuCl·Me 2 S). The method displayed a rapid reaction rate (within 10 min), wide functional group tolerance (27 unprotected peptides were cyclized), and up to 86% isolated yield. The obtained highly conjugated cyclic peptide linker, formed through C–H alkynylation, can be directly applied to live-cell imaging as a fluorescent probe without further attachment of fluorophores.