Late-Stage Macrocyclization of Bioactive Peptides with Internal Oxazole Motifs via Palladium-Catalyzed C-H Olefination

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 d-C(sp(2))-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.

Automated summary

In this study, a late-stage site-selective functionalization of oxazole-containing peptides was achieved through palladium-catalyzed d-C(sp(2))-H olefination of phenylalanine, tryptophan, and tyrosine residues. The strategy utilizes oxazole motifs as internal directing groups, providing access to oxazole-containing peptide macrocycles with bioactivities.