Gyimesi-Forrás Krisztina, Maier Norbert M, Kökösi József, Gergely András, Lindner Wolfgang
Department of Analytical Chemistry and Food Chemistry, University of Vienna, Vienna, Austria.
Chirality. 2009 Jan;21(1):199-207. doi: 10.1002/chir.20640.
The normal phase mode liquid chromatographic enantiomer separation capability of a quinine tert-butyl-carbamate-type chiral stationary phase (CSP) has been investigated for a set of polar [1,5-b]-quinazoline-1,5-dione derivatives. This class of chiral heterocycles is currently under development as potential alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and/or N-methyl-D-aspartic acid (NMDA) receptor antagonists. The effect of the nature and concentration of polar modifier, i.e., ethanol and isopropanol, in n-hexane-based mobile phases, as well as the substituent pattern of the phenyl ring attached to the quinazolone framework on retention factor, enantioselectivity, and resolution was investigated. The Soczewiński competitive adsorption model was used to describe the relationship between the retention and the binary mobile phase compositions. According to this model, linear plots of the logarithms of retention factor versus molar fractions of the polar modifiers were obtained over a wide concentration range (X(B) between 0.15 and 0.35). Addition of equimolar ethanol yields higher resolution than isopropanol, R(S) values ranging between 1.54 and 2.75, whereas the latter allows to achieve moderately increased enatioselectivity. The resolution was further improved by using a ternary mixture of n-hexane:methanol:isopropanol/85:5:10 (v/v). The most pronounced selectivity factor alpha and resolution R(S) values were obtained for the para-hydroxy substituted compound, indicating that chiral recognition is sensitive to steric and stereoelectronic factors. In the course of optimization, the temperature-dependence on the chiral separation was also investigated. It turned out that the enantiomer separation is predominantly enthalpically driven in normal phase mode.
已对一组极性[1,5 - b] - 喹唑啉 - 1,5 - 二酮衍生物，研究了氨基甲酸叔丁酯型奎宁手性固定相（CSP）的正相模式液相色谱对映体分离能力。这类手性杂环目前正作为潜在的α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸（AMPA）和/或N - 甲基 - D - 天冬氨酸（NMDA）受体拮抗剂进行开发。研究了基于正己烷的流动相中极性改性剂（即乙醇和异丙醇）的性质和浓度，以及连接在喹唑啉酮骨架上的苯环取代模式对保留因子、对映体选择性和分离度的影响。使用索切夫斯基竞争吸附模型来描述保留与二元流动相组成之间的关系。根据该模型，在较宽的浓度范围（X(B)在0.15至0.35之间）内，得到了保留因子对数与极性改性剂摩尔分数的线性图。加入等摩尔乙醇比异丙醇产生更高的分离度，R(S)值在1.54至2.75之间，而后者能实现适度提高的对映体选择性。通过使用正己烷：甲醇：异丙醇/85:5:10（v/v）的三元混合物，分离度进一步提高。对羟基取代的化合物获得了最显著的选择性因子α和分离度R(S)值，表明手性识别对空间和立体电子因素敏感。在优化过程中，还研究了温度对手性分离的影响。结果表明，在正相模式下，对映体分离主要由焓驱动。
