N-Linked Peptidocalix[4]arene Bisureas as Enantioselective Receptors for Amino Acid Derivatives

Bisurea calix[4]arenes 1 and 2 possessing l-amino acid moieties at the lower rim were synthesized by reaction of the methyl esters of glycine, l-alanine, or l-isoleucine with the appropriate isocyanate (12 or 13), obtained with a safe and efficient Curtius rearrangement from the corresponding carboxylic acid derivatives. The conformational properties of the ligands 1 and 2 were investigated by means of a combined NMR and molecular modeling study which evidences that they are deeply influenced by strong intramolecular H-bonds between the urea NH groups and the vicinal phenolic oxygen atoms or the opposite urea CO group. Complexation studies performed by ESI-MS and NMR spectroscopy in acetone solution show that the binding ability of these bisurea hosts decreases by increasing the side chain size of the amino acid. Host 2b has a remarkable binding ability for the N-acetyl-d-phenylalaninate anion with an interesting enantioselectivity ( / = 4.14), which is explained on the basis of a three-point interaction mode of binding.