Palladium-Catalyzed Late-Stage Maleimidation of Phenylalanine-Containing Peptides

The incorporation of bioactive fragments or non-natural covalent linkages has shown to significantly improve the chemical stability and biological activity of peptides. In this study, we have developed a novel methodology for site-selective Pd-catalyzed maleimidation of phenylalanine-containing peptides. This synthetic strategy offers a straightforward and efficient approach for the construction of maleimide-phenylalanine covalent peptide conjugates. The merit of this method includes broad substrate tolerance, exclusive formation of Heck-type products, and excellent chemoselectivity.