Effect of Side Chains on Turns and Helices in Peptides of β³-Aminoxy Acids

We have investigated, using NMR, IR, and CD spectroscopy and X-ray crystallography, the conformational properties of peptides 1−10 of β3-aminoxy acids (NH2OCHRCH2COOH) having different side chains on the β carbon atom (e.g., R = Me, Et, COOBn, CH2CH2CHCH2, i-Bu, i-Pr). The β N−O turns and β N−O helices that involve a nine-membered-ring intramolecular hydrogen bond between NHi+2 and COi, which have been found previously in peptides of β2,2-aminoxy acids (NH2OCH2CMe2COOH), are also present in those β3-aminoxy peptides. X-ray crystal structures and NMR spectral analysis reveal that, in the β N−O turns and β N−O helices induced by β3-aminoxy acids, the N−O bond could be either anti or gauche to the Cα−Cβ bond depending on the size of the side chain; in contrast, only the anti conformation was found in β2,2-aminoxy peptides. Both diamide 1 and triamide 9 exist in different conformations in solution and in the solid state: parallel sheet structures in the solid state and predominantly β N−O turn and β N−O helix conformations in nonpolar solvents. Theoretical studies on a series of model diamides rationalize very well the experimentally observed conformational features of these β3-aminoxy peptides.