No abstract

The perfluoroheteroaromatic reagent pentafluoropyridine has proved to be a highly reactive electrophile, undergoing SAr arylation reactions in the presence of a range of nucleophilic peptide side chains (i.e. cysteine, tyrosine, serine and lysine) under mild conditions. Moreover, we have shown how one-step peptide-modification using perfluoroheteroaromatics can deliver enhanced proteolytic stability in pharmaceutically-relevant peptides such as oxytocin.

The SAr arylation of peptides with perfluoroaromatics provides a route by which to install a useful chemical handle that enables both F-NMR analysis and further chemical modification. However, chemo-selective arylation in peptides containing multiple nucleophilic side chains currently presents a challenge to the field. Herein, we demonstrate that employing 2,2,2-trifluoroethanol (TFE) as a solvent in peptide SAr reactions significantly improves nucleophile-selectivity when compared to N,N'-dimethylformamide (DMF).