Structural scaffold of 18-crown-6 tetracarboxylic acid for optical resolution of chiral amino acid: X-ray crystal analyses and energy calculations of complexes of d- and l-isomers of tyrosine, isoleucine, methionine and phenylglycine

Abstract

To clarify the structural scaffold of (+)-18-crown-6 tetracarboxylic acid ((+)-18C6H₄) for the optical resolution of a chiral amino acid, the crystal structures of its equimolar complexes with L- and D-isomers of tyrosine (Tyr), isoleucine (Ile), methionine (Met) and phenylglycine (PheG) were analysed by X-ray diffraction methods. (+)-18C6H₄ took very similar conformations for all complexes. Although the chemical structure of (+)-18C6H₄ is C2-symmetric, it took a similar asymmetric ring conformation of radius ca. 6.0 Å. In all complexes, the amino group of chiral amino acids was located near the center of the ring and formed three hydrogen bonds and five electrostatic interactions with eight oxygen atoms of the ether ring and carboxyl groups. Also, the Cα atom of chiral amino acids participated in Cα–H⋯O interaction with the oxygen atom of (+)-18C6H₄. In contrast, the carboxyl group of chiral amino acids did not directly interact with (+)-18C6H₄. These results indicate that the structural scaffold of (+)-18C6H₄ for the optical resolution of chiral amino acids is mainly based on the mode of interaction of (+)-18C6H₄ with the amino and Cα–H groups of chiral amino acids. The differences in interaction pattern and binding energy between the L- and D-isomers of each amino acid are discussed in relation to the chiral recognition of (+)-18C6H₄.