Side-Chain Modification of Peptides Using a Phosphoranylidene Amino Acid

The flexible variation of peptidomimetics is of great interest for the identification of optimized protein ligands. Here we present a general concept for introducing side-chain modifications into peptides using triarylphosphonium amino acids. Building blocks 4a and 4b are activated for amidation and incorporated into stable peptides. The obtained phosphoranylidene peptides undergo Wittig olefinations and 1,3-dipolar cycloaddition reactions, yielding peptidomimetics with vinyl ketones and 5-substituted 1,2,3-triazoles as non-native peptide side chains.