Synthesis of Tetrafluorinated Aromatic Amino Acids with Distinct Signatures in 19F NMR

Fluorinated amino acids serve as powerful tools in protein chemistry. We synthesized a series of para-substituted tetrafluorophenylalanines via the regioselective SNAr chemistry of the commercially available pentafluorophenylalanine Boc-Z. These novel unnatural amino acids display distinct 19F NMR signatures, making them powerful tools for analyzing protein–membrane interactions with NMR spectroscopy.