Electrochemically Enabled C-Terminal Peptide Modifications.

Modified peptides serve as promising therapeutic leads, valuable tools for chemical biology, and diverse functional materials. Synthetic strategies which enable the direct modification of native peptide sequences are particularly attractive for the rapid generation of designer peptides. This chapter details an operationally simple electrochemical approach to the modification of the peptide C-terminus, which proceeds via direct anodic oxidation of C-terminal peptide carboxylic acids. Electrochemical decarboxylation affords a key N,O-acetal intermediate, which can be engaged with various nucleophiles. Herein, step-by-step protocols for C-terminal arylation and sulfonylation are presented to highlight the utility of the method for the preparation of valuable functionalized peptides.