Metal-Free Selective Modification of Secondary Amides: Application in Late-Stage Diversification of Peptides

Here we solve a long-standing challenge of the site-selective modification of secondary amides and present a simple two-step, metal-free approach to selectively modify a particular secondary amide in molecules containing multiple primary and secondary amides. Density functional theory (DFT) provides insight into the activation of C-N bonds. This study encompasses distinct chemical advances for late-stage modification of peptides thus harnessing the amides for the incorporation of various functional groups into natural and synthetic molecules.

Automated summary

This study successfully addresses the challenge of selectively modifying a specific secondary amide in molecules containing multiple primary and secondary amides, and provides insight into the activation of C-N bonds through density functional theory. It represents significant chemical advances for late-stage modification of peptides and the incorporation of various functional groups into natural and synthetic molecules.