Quinoline-Based Amide Foldamers with One-Handed Chirality Induced by an Asymmetric Plane

Abstract

A quinoline-containing cyclophane derivative with planar chirality was rationally designed and synthesized based on [2.2]paracyclophane (PCP) and used as a structural unit to induce the absolute one-handed helical conformation of quinoline foldamers. 1H NMR, X-ray crystal diffraction, and chiral HPLC studies demonstrate that the trimers are a pair of racemic enantiomers, and the P- and M-helical conformers could be separated by a chemical method. X-ray crystal diffraction and CD studies reveal that the R- and S-asymmetric planes are always associated with P- and M-helical conformations, respectively, which differs from the chiral induction mediated by chiral carbon-centered groups. Variable-temperature 1H NMR experiments further demonstrate that chiral conformations of these foldamers are thermally stable with no observable interconversion between the P- and M-helices even at elevated temperatures.