Post-Assembly Modification of Head-to-Tail Cyclic Peptides by Methionine-Directed β-C(sp3)-H Arylation

Peptide modification by C(sp(3))-H functionalization of internal residues remains a major challenge due to the inhibitory effect of peptide bonds. In this work, we developed a methionine-directed beta-C(sp(3))-H arylation method for internal alanine functionalization. By tuning the sigma(C-C) bond rotation of internal Ala through head-to-tail cyclization, we overcame the inhibitory effect and functionalized a wide range of head-totail cyclic peptides with aryl iodides with excellent position selectivity.

Automated summary

This study developed a method for modifying internal alanine in peptides through beta-C(sp(3))-H arylation by tuning the sigma(C-C) bond rotation of internal Ala through head-to-tail cyclization. This method overcame the inhibitory effect and achieved excellent position selectivity in functionalizing a wide range of head-totail cyclic peptides with aryl iodides.