Late-Stage Macrocyclization of Bioactive Peptides with Internal Oxazole Motifs via Palladium-Catalyzed C–H Olefination
Shu Liu, Chuangxu Cai, Zengbing Bai, Wangjian Sheng, Jiantao Tan, Huan Wang
Abstract
Oxazole is an important pharmacophore and exists in the backbone of many bioactive peptide natural products and peptidomimetics. Efficient methods for the synthesis and direct functionalization of complex oxazole-containing peptides are in high demand. Herein, we report the late-stage site-selective functionalization of oxazole-containing peptides via palladium-catalyzed δ-C(sp2)–H olefination of phenylalanine, tryptophan, and tyrosine residues. This strategy utilizes oxazole motifs as internal directing groups and provides access to oxazole-containing peptide macrocycles with bioactivities.
Topics & Concepts
OxazoleChemistryPharmacophorePeptidomimeticCombinatorial chemistryPeptidePalladiumStereochemistryCatalysisTyrosineOrganic chemistryBiochemistryCatalytic C–H Functionalization MethodsSynthesis and Catalytic ReactionsClick Chemistry and Applications