依托度酸及其中间体依托度酸甲酯的对映体分离研究

Enantioseparation of Etodolac and its Intermediate on Chiral Stationary Phase by High Pherformance Liquid Chromatography

在自制的涂敷型纤维素三(3,5-二甲基苯基氨基甲酸酯)(CDMPC)和P irkle型(S,S)-W helk-O1两种手性柱上,对依托度酸及其中间体进行了对映体分离。考察了在流动相正己烷中,不同的醇类添加剂以及醇类添加剂的浓度对手性分离的影响,当流动相为正己烷-仲丁醇(0.39 mol/L),流速1.0 mL/m in,温度25℃时,对映体在CDMPC柱上分离效果好。研究了溶质的体积大小及空间立体结构因素对手性分离的影响。结果发现,对(S,S)-W helk-O 1柱,溶质与固定相之间以氢键为主的吸引作用是手性识别的主要因素,而对于CDMPC柱,溶质在手性空腔中的空间适应性很可能是手性识别的关键。

Cellulose and cellulose derivatives are biopolymers which are often used as stationary phases for the separation of enantiomers. Describing the mechanism of such separations is a difficult task due to the complexity of these stationary phases. In this study, the separation of etodolac and its intermediate was studied on two chlral columns-cellulose tris （3,5-dimethyphenylcarbamate （CDMPC） and （S,S）-Whelk-O1 chiral columns. The influence of the structures of the analytes on the chiral separation was investigated. The mobile phase composition including the concentration and type of the alcohol modifier in hexane was varied, and the influence on the retention factor（k＇） for each enantiomer, the separation factor（α） and the resolution （R） was studied. Etodolac and its intermediate can be baseline separated on CDMPC using hexane-sec-butanol（0. 39 mol./L） as eluent, at a flow rate of 1.0 mL/min and at 25℃. Then the two different chiral recognition mechanisms were discussed and compared. On （S, S）-Whelk-O1 ,the attractive interactions, especially hydrogen bonding interaction, between chiral stafionary phase and solute are the key factor for retention and chiral recognition, on CDMPC, the steric fit of solute into the chiral cavity maybe the predominant factor for the chiral recognition of etodolac and its intermediate.