The first example of linear peptides containing a N-trifluoroethylated backbone amide linkage and the surprising solution dynamics observed by 19F NMR

The α-amino group of (l)phenylalanine methyl ester was trifluoroethylated using (2,2,2-trifluoroethyl)phenyliodonium N,N-bis(trifluoromethylsulfonyl)imide. A dipeptide Gly(l)Phe containing a trifluoroethylated peptide bond was synthesized by removing the α-amino proton of Nα-trifluoroethyl (l)phenylalanine methyl ester followed by coupling with Nα-phthaloyl glycine acid fluoride. The dipeptide was further coupled with (l)leucine methyl ester under conventional carboxyl activation conditions to provide two diastereomers of the tripeptide Gly(d,l)Phe(l)Leu. The solution dynamic behavior of the tripeptide was investigated as a function of solvents, by NOESY and variable temperature (VT) 19F NMR experiments.