Liquid chromatographic enantiomer separations of novel quinazolone derivatives on quinine carbamate based chiral stationary phases using hydro-organic mobile phases

被引:12
作者
Gyimesi-Forrás, K
Kökösi, J
Szász, G
Gergely, A
Lindner, W
机构
[1] Univ Vienna, Inst Analyt Chem, A-1090 Vienna, Austria
[2] Semmelweis Univ, Dept Pharmaceut Chem, H-1092 Budapest, Hungary
关键词
enantiomer separation; chiral stationary phases; LC; mobile phase composition; quinazolone derivatives; quinine carbamate;
D O I
10.1016/j.chroma.2004.06.090
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Quinine carbamate-type weak chiral anion-exchange selectors (SOs) and the respective chiral stationary phases (CSPs) have been used for the direct liquid chromatographic enantiomer separation of a wide range of chiral acids. In the present work, we demonstrate that these CSPs can also be extended to chiral discrimination of a set of neutral polar potential NMDA (N-methyl-D-aspartic acid) and/or AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) antagonist imidazo-quinazoline-dione derivatives (selectands, SAs) using acetonitrile and methanol containing hydro-organic and buffered mobile phases. The influence of mobile phase composition, column temperature and structure variation of the SAs and SOs on retention and enantioselectivity was systematically investigated to gain insight into the overall chiral recognition mechanism. As was expected for the reversed-phase mode, acetonitrile has a stronger eluotropic effect compared to methanol. Except for two analytes, the acetonitrile containing mobile phases provided baseline resolution (R-s) of the enantiomers with R-s values ranging between 1.68 and 2.76. Using methanol as the organic modifier enhanced the enantioselectivity. The enthalpic and entropic terms for the SO-SA association were calculated from the linear van't Hoff plots. Data reveal that the enantiomer separations are predominantly enthalpically driven. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:59 / 67
页数:9
相关论文
共 23 条
[1]   A POTENT, ORALLY-ACTIVE, BALANCED AFFINITY ANGIOTENSIN-II AT(1) ANTAGONIST AND AT(2) BINDING INHIBITOR [J].
DELASZLO, SE ;
QUAGLIATO, CS ;
GREENLEE, WJ ;
PATCHETT, AA ;
CHANG, RSL ;
LOTTI, VJ ;
CHEN, TB ;
SCHECK, SA ;
FAUST, KA ;
KIVLIGHN, SS ;
SCHORN, TS ;
ZINGARO, GJ ;
SIEGL, PKS .
JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (21) :3207-3210
[2]   GRADIENT ELUTION IN HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY .2. PRACTICAL APPLICATION TO REVERSED-PHASE SYSTEMS [J].
DOLAN, JW ;
GANT, JR ;
SNYDER, LR .
JOURNAL OF CHROMATOGRAPHY, 1979, 165 (01) :31-58
[3]  
FRANCOTTE E, 1997, CHEM ANAL SERIES MON, V142, P633
[4]  
KOKOSI J, Patent No. 208975
[5]   High-performance liquid chromatographic enantiomer separation and determination of absolute configurations of phosphinic acid analogues of dipeptides and their α-aminophosphinic acid precursors [J].
Lämmerhofer, M ;
Hebenstreit, D ;
Gavioli, E ;
Lindner, W ;
Mucha, A ;
Kafarski, P ;
Wieczorek, P .
TETRAHEDRON-ASYMMETRY, 2003, 14 (17) :2557-2565
[6]   Computerized optimization of the high-performance liquid chromatographic enantioseparation of a mixture of 4-dinitrophenyl amino acids on a quinine carbamate-type chiral stationary phase using DRYLAB [J].
Lammerhofer, M ;
DiEugenio, P ;
Molnar, I ;
Lindner, W .
JOURNAL OF CHROMATOGRAPHY B, 1997, 689 (01) :123-135
[7]   Quinine and quinidine derivatives as chiral selectors .1. Brush type chiral stationary phases for high-performance liquid chromatography based on cinchonan carbamates and their application as chiral anion exchangers [J].
Lammerhofer, M ;
Lindner, W .
JOURNAL OF CHROMATOGRAPHY A, 1996, 741 (01) :33-48
[8]  
LINDNER W, Patent No. 9702888
[9]  
Maier NM, 1999, CHIRALITY, V11, P522, DOI 10.1002/(SICI)1520-636X(1999)11:7<522::AID-CHIR2>3.0.CO
[10]  
2-U