Locking Interconversion of Aromatic Oligoamide Foldamers by Intramolecular Side-chain Crosslinking: toward Absolute Control of Helicity in Synthetic Aromatic Foldamers

A series of foldamers of 8-amino-2-quinoline carboxylic acid were stapled by intramolecular ring-closing olefin metathesis to generate the constrained aromatic foldamers with varying lengths of hydrocarbon side-chains. Investigations clearly revealed that the side-chain crosslinkers are capable of completely locking the interconversions of the stapled aromatic foldamers over a wide range of temperatures in CDCl3, even in C2D2Cl4. Hence, the stapled foldamers with the short hydrocarbon crosslinker can be easily separated by silica-gel chromatography to generate foldamers with stable, absolute one-handed helicity. But the stapled foldamer with the longer crosslinker is inseparable even by chiral HPLC presumably due to the fortuitous identical polarity of the diastereomer.