(2S4R)- and (2S4S)-Perfluoro-tert-butyl 4-Hydroxyproline: Two ConformationallyDistinct ProlineAmino Acids for Sensitive Application in 19F NMR

摘要

(2S,4R)- and (2S,4S)-perfluoro-tert-butyl 4-hydroxyproline were synthesized (as Fmoc-, Boc-, and free amino acids) in 2–5 steps. The key step of each synthesis was a Mitsunobu reaction with perfluoro-tert-butanol, which incorporated a perfluoro-tert-butyl group, with nine chemically equivalent fluorines. Both amino acids were incorporated in model α-helical and polyproline helix peptides. Each amino acid exhibited distinct conformational preferences, with (2S,4R)-perfluoro-tert-butyl 4-hydroxyproline promoting polyproline helix. Peptides containing these amino acids were sensitively detected by ¹⁹F NMR, suggesting their use in probes and medicinal chemistry.