H N.M.R. studies of protected α-aminoisobutyric acid containing peptides: chemical shift nonequivalence of benzyloxycarbonyl methylene protons

Abstract

The benzylic methylene protons in a large number of benzyloxycarbonyl α-aminoisobutyric acid (Z-Aib) containing peptides, show chemical shift nonequivalence. The magnitude of the geminal nonequivalence is correlated with the involvement of the urethane carbonyl group, in an intramolecular hydrogen bond. Studies of the model compounds Z-Aib-Aib-Ala-NHMe, and Z-Aib-Aib-Aib-Pro-OMe clearly establish the presence of intramolecular hydrogen bonds, involving the urethane CO group. In both compounds marked anisochrony of the benzylic methylene protons is demonstrated. In Z-Aib-Aib-Pro-OMe, where a 4 → 1 hydrogen bonded β-turn is not possible, the benzylic -CH₂- protons appear as a singlet in CDCl₃ and have a very small chemical shift difference in (CD₃)₂SO. The observation of such nonequivalence is of value in establishing whether the amino terminal Aib-Pro β-turn is retained in large peptide fragments of alamethicin.