Conformational Preferences of Cyclopentane-Based Oligo-δ-peptides in the Gas Phase and in Solution.

The conformational preferences of oligomers of δ-amino acid (δAc a) with a cyclopentyl constraint in the C -C bond of the backbone were investigated by using DFT methods in the gas phase and in solution. The folded structures with C H-bonded pseudocycles were most preferred for dimer and tetramer of δAc a residues both in chloroform and water. However, for the hexameric Ac-(δAc a) -NHMe, the mixed H helical structure was found to be most preferred in chloroform (populated at 68 %), whereas the H helical structure was the most dominant conformation in water (populated at 60 %). The stability of the former was ascribed to the intrinsic conformational energy, whereas the solvation free energy was crucial to stabilize the latter. Pyrrolidine-substituted analogues of the hexameric Ac-(δAc a) -NHMe, with adjacent amine diads that are almost exactly one turn apart with two nitrogen atoms separated by ca. 5.5 Å, adopted helical structures. They are potential catalysts in nonpolar and polar solvents as they have similar structures to a helical 1 : 2 α:β-heptapeptide that exhibited good catalytic performance in the crossed aldol condensation.