Molecular recognition and phase transfer of underivatized amino acids by a foldable artificial host

A novel molecular host 5 for amino acid zwitterions is described. The covalent connection of a chiral bicyclic guanidinium salt as an anchor function for the carboxylate and a triaza-crown ether as an ammonium binding moiety in combination with a strongly hydrophobic silyl ether serves to complex and transfer amino acids from water into dichloromethane with unprecedented efficiency. Quantitation of the extraction process by radiometry revealed a clean 1:1 stoichiometry and gives evidence for the zwitterion as the species undergoing phase transfer. Even small hydrophilic (Ser, Gly) but no charged amino acids were extracted better by factors up to 3000-fold than by a previously reported host of similar design (Galan, A.; Andreu, D.; Echavarren, A. M.; Prados, P.; de Mendoza, J. J. Am. Chem. Sec. 1992, 114, 1511-1512). Some enantioselection in the transfer of phenylalanine was observed (40% ee).