Macrocyclization of Biaryl-Bridged Peptides through Late-Stage Palladium-Catalyzed C(sp2)-H Arylation

Org Lett. 2019 Oct 18;21(20):8225-8228. doi: 10.1021/acs.orglett.9b02945. Epub 2019 Sep 26.

Abstract

Macrocyclic peptides are promising scaffolds of bioactive compounds and clinical therapeutics. Herein, we develop a strategy for the macrocyclization of biaryl-bridged peptides through late-stage Pd-catalyzed C(sp2)-H arylation. This method displays broad substrate scope and high efficiency in the synthesis of peptide conjugates with various bioactive molecules. Furthermore, we applied this method to prepare peptide macrocycles with aryl-aryl cross-links. Our results show the effectiveness of backbone amide groups as directing groups in Pd-catalyzed C-H functionalization of peptides.

Publication types

  • Research Support, Non-U.S. Gov't