Expedient Synthesis of Fmoc-(S)-γ-Fluoroleucine and Late-Stage Fluorination of Peptides

A concise synthesis of ( S )-γ-fluoroleucine is described in five steps from commercially available compounds, with an overall yield of 57%. The Markovnikov hydrofluorination reaction of the unsaturated amino acid precursor as last step of the synthesis proved to be effective. This fluorination can also be performed directly on a short peptide model with the same efficiency. This reaction could be in principle applicable for the preparation of radiolabeled amino acids and peptides.