Water-Soluble Calix[4]resorcinarenes with Amino Acid Moieties at the Upper Rim: Synthesis, Characterization, and Properties

A series of amino acid-functionalized calix[4]resorcinarenes was synthesized via a Mannich reaction involving four calix[4]resorcinarenes bearing ethyl, propyl, iso-butyl, or benzyl substituents at the lower rim, five amino acids (both chiral and achiral), and aqueous formaldehyde (37%). The structures of the synthesized compounds were confirmed by IR and NMR spectroscopy and ESI mass spectrometry. The water solubility of the products significantly enhanced compared to that of the parent calix[4]resorcinarenes. This is especially true of the synthesized calix[4]resorcinarenes bearing N-methyl-L-alanine moieties: at room temperature, the pH of aqueous solutions of these compounds was lower by more than 2.0 units compared to their respective precursors. In contrast, the parent benzyl-substituted calix[4]resorcinarenes and its amino acid derivatives showed a relatively low water solubility. Notably, the L-proline calix[4]resorcinarene derivative with iso-butyl substituents at the lower rim demonstrated potential for application in asymmetric catalysis.