Long-range chemical ligation from N→N acyl migrations in tryptophan peptides via cyclic transition states of 10- to 18-members

Abstract

Chemical ligations to form native peptides from N→N acyl migrations in Trp-containing peptides via 10- to 18-membered cyclic transition states are described. In this study, a statistical, predictive model that uses an extensive synthetic and computational approach to rationalize the chemical ligation is reported. N→N acyl migrations that form longer native peptides without the use of Cys/Ser/Tyr residues or an auxiliary group at the ligation site were achieved. The feasibility of these traceless chemical ligations is supported by the N-C bond distance in N-acyl isopeptides. The intramolecular nature of the chemical ligations is justified by using competitive experiments and theoretical calculations. Going the distance: Chemical ligations to form native peptides from N→N acyl migrations in Trp-containing peptides via 10- to 18-membered cyclic transition states are described (see scheme; Bn: benzyl; Z: benzyloxycarbonyl). The ligations are achieved without the use of Cys/Ser/Tyr residues or an auxiliary group. This new approach represents a significant development in the field. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.