One-Pot Synthesis of Alkynyl-Conjugated Phenylalanine Analogues for Peptide-Based Fluorescent Imaging.

A series of unnatural amino acids featuring conjugated aryl-alkyne side chains was synthesized from tyrosine via a one-pot hydroxyl group activation and copper-free Sonogashira cross-coupling. This efficient strategy enabled rapid access to modified phenylalanine analogues and the discovery of a fluorescent lead compound with enhanced photophysical properties and sensitivity to lipid-rich environments. Excitation of the alkenyl-conjugated lead analogue in dipeptides, without quenching or interference from intrinsic proteinogenic fluorophores demonstrates its potential for biological imaging applications.