Molecular Recognition of Aliphatic L-Amino Acids by D-Mandelic acid

Biological Science and Technology, Tokai University* Daito Chemical Co. Ltd.**
â—‹Taira Kimino* Yukio Takahasi** Isao Fujii*

The production of non-naturally occurring-amino acids has great importance in the pharmaceutical industry. An aqueous solution of racemic compound and optically pure mandelic acid [MAN] has been applied in the diastereomer salt separation. Although MAN is widely used in the resolution of such amino acids, the crystal structures of alanine, phenylalanine and methionine recognized by MAN have only been studied. From the limited information, the MAN molecules have been considered to recognize the hydrophilic groups of amino acid by its hydrophilic groups, and pack in a specific way to form hydrophobic and hydrophilic layers that are well separated. The MAN molecules mainly stabilized the hydrophobic layers by the CH...pai interactions among phenyl groups and the hydrophobic groups of amino acids.
We recently reported that the chiral interface (or surface) between hydrophobic and hydrophilic layers formed by MAN strongly recognizes the chirality of L-cysteine. In this study, we focused to disclose the varieties of chiral interface formed by MAN molecules, especially on the size of hydrophobic pocket. The complexes of L-2-aminobutanoic acid, L-norvaline and L-norleucine with D-MAN were examined by X-ray analysis to disclose the fashion of interactions between the L-amino acids and D-MAN. It reveals that the chiral interface plays an important role for the molecular recognition by MAN, which allows fractional crystallization of the aliphatic chain amino acids.