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

The conformational preferences of oligomers of δ-amino acid (δAc5 a) with a cyclopentyl constraint in the Cβ -Cγ bond of the backbone were investigated by using DFT methods in the gas phase and in solution. The folded structures with C10 H-bonded pseudocycles were most preferred for dimer and tetramer of δAc5 a residues both in chloroform and water. However, for the hexameric Ac-(δAc5 a)6 -NHMe, the mixed H16/14 helical structure was found to be most preferred in chloroform (populated at 68 %), whereas the H14 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-(δAc5 a)6 -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.