Chem. Pharm. Bull. 54(4) 452—457 (2006)

est, because the biologically effective chiral drug is either of enantiomers and the antipode is regarded as the impurity showing sometime high toxicity. Recently, the HPLC with chiral stationary phases (CSPs) has been extensively used to achieve the direct enantiomer separation. Crown ether, first introduced by Pedersen in 1967, was shown by Cram et al. to resolve enantiomers by the host-guest complexation. Since then, the optically active crown ether derivatives have been widely used for the optical syntheses, resolutions and analyses of chiral amino compounds. A novel CSP derived from crown ether, which was prepared by immobilizing ( )18-crown-6 tetracarboxylic acid (( )-18C6H4) on 3-aminopropylsilanized silica-gel, was reported by Machida et al. to show the effective enantiomer separation of amino compounds, and has been widely used as a chiral selector for the primary amines in capillary electrophoresis (CE) and HPLC. As for the enantiomer separation of D/L-amino acids by HPLC with ( )-18C6H4 immobilized CSP, it has been generally accepted that L-isomers are commonly eluted prior to D-amino acids, indicating that D-amino acids form more stable interactions with ( )-18C6H4 than L-amino acids. Because no systematic investigation was performed on the discrimination mechanism of ( )-18C6H4 between Dand Lisomers, we recently analyzed the crystal structures of the complexes of ( )-18C6H4 with Dand L-isomers of tyrosine, isoleucine, methionine and phenylglycine, and clarified the common structural scaffold of ( )-18C6H4 for D/L-separation of these chiral amino acids. On the other hand, concerning the first elution rule of Lamino acid in CE with ( )-18C6H4, an exception was recently observed for the chiral separation of L/D-serine (Ser). To clarify why D-Ser is eluted prior to L-Ser, we investigated the chiral interactions of ( )-18C6H4–L-Ser (L1) and ( )-18C6H4–D-Ser (D1) complexes by the X-ray single crystal analyses. In addition, the crystal structures of ( )18C6H4–L-glutamic acid (L-Glu) (L2) and ( )-18C6H4–DGlu (D2) complexes were also analyzed, as one of the examples according to the first elution rule of L-isomer. In this paper, we report the common as well as different interaction modes between the Land D-isomers of these two amino acids. The atomic numberings of ( )-18C6H4, Ser and Glu are given in Fig. 1.