氨基酸离子液体液液萃取拆分美托洛尔的研究  

Racemic metoprolol separation by enantioselective liquid-liquid extraction with amino acid ionic liquids

作　　者：单若妮 崔兴[1,2] 丁琦 何潮洪 SHAN Ruo-ni;CUI Xing;DING Qi;HE Chao-hong(Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology,College of Chemical and Biological Engineering,Zhejiang University,Hangzhou 310027,China;Institute of Zhejiang University-Quzhou,Quzhou 324000,China)

机构地区：[1]浙江省化工高效制造技术重点实验室,浙江大学化学工程与生物工程学院,浙江杭州310027 [2]浙江大学衢州研究院,浙江衢州324000

出　　处：《高校化学工程学报》2019年第6期1444-1449,共6页Journal of Chemical Engineering of Chinese Universities

基　　金：国家自然科学基金(21576231)

摘　　要：美托洛尔是一种常用的β1受体阻断剂,在临床上被广泛用于心血管疾病的治疗。研究表明S-对映体具有较强的药效,而R-对映体与一些毒副作用相关。因此获得单一构型的S-美托洛尔对提高药物的安全性和有效性有重要意义。采用氨基酸离子液体作为手性识别剂用于手性液液萃取拆分美托洛尔对映体。研究氨基酸离子液体种类和浓度,有机溶剂,美托洛尔初始浓度,水相pH以及温度对萃取分配行为的影响。结果表明,当采用1,2-二氯乙烷作为有机溶剂,1-丁基-3-甲基咪唑L-色氨酸([Bmim][L-Trp])作为手性识别剂,手性识别剂和美托洛尔浓度分别为30和2mmol×L^-1,水相pH为8.5,温度为25℃时,对映体选择性达到1.29。研究成果为手性液液萃取拆分法的工业化应用提供参考。Metoprolol is a selective β1 receptor blocking agent, which has been widely used in the treatment of cardiovascular diseases. Studies show that(S)-metoprolol has better treating performance, while(R)-metoprolol is related to side effects. Therefore, obtaining optically pure enantiomersers of(S)-metoprolol is of great significance to improve the safety and effectiveness. Amino acid ionic liquids were used as chiral selector for the enatioseparation of metoprolol enantiomers by liquid-liquid extraction. And the effects of chemical structure and concentration of amino acid ionic liquids, organic solvents, initial concentration of metoprolol, aqueous phase pH and temperature were investigated. The results show that the enantioselectivity reaches up to 1.29 at pH 8.5, 25 ℃ when 1,2-dichloroethane is used as the organic solvent, 1-butyl-3-methylimidazolium L-tryptophan is used as the chiral selector, and the chiral selector and metoprolol concentration are 30 and 2 mmol×L^-1, respectively. The results provide important support for the potential industrialization of enantioselective liquid-liquid extraction for metoprolol.

关 键 词：美托洛尔 手性 液液萃取 氨基酸离子液体 

分 类 号：TQ028.4[化学工程]