On-Resin Ugi Reaction for C-Terminally Modified and Head-to-Tail Cyclized Antibacterial Peptides

Here we report a method to synthesize C-terminally modified peptides on resin. A four-component Ugi reaction of isocyanide resin, an Fmoc-protected amino acid, an amine, and a 6-nitroveratrylaldehyde gives C-terminal photocaged peptide amides, which can be photolyzed to generate C-terminal peptide amides. Changing the amine component in the Ugi reaction gives peptides with different C-terminal modifications including substituted anilides,...