Jin Kab Bong, Kim Hee Eun, Hyun Myung Ho
Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan, Republic of Korea.
Chirality. 2014 May;26(5):272-8. doi: 10.1002/chir.22318. Epub 2014 Mar 27.
Mexiletine, an effective class IB antiarrhythmic agent, and its analogs were resolved on three different crown ether-based chiral stationary phases (CSPs), one (CSP 1) of which is based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid and the other two (CSP 2 and CSP 3) are based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6. Mexiletine was resolved with a resolution (R(S)) of greater than 1.00 on CSP 1 and CSP 3 containing residual silanol group-protecting n-octyl groups on the silica surface, but with a resolution (R(S)) of less than 1.00 on CSP 2. The chromatographic behaviors for the resolution of mexiletine analogs containing a substituted phenyl group at the chiral center on the three CSPs were quite dependent on the phenoxy group of analytes. Namely, mexiletine analogs containing 2,6-dimethylphenoxy, 3,4-dimethylphenoxy, 3-methylphenoxy, 4-methylphenoxy, and a simple phenoxy group were resolved very well on the three CSPs even though the chiral recognition efficiencies vary with the CSPs. However, mexiletine analogs containing 2-methylphenoxy group were not resolved at all or only slightly resolved. Among the three CSPs, CSP 3 was found to show the highest chiral recognition efficiencies for the resolution of mexiletine and its analogs, especially in terms of resolution (R(S)).
美西律是一种有效的IB类抗心律失常药物，其类似物在三种不同的基于冠醚的手性固定相（CSP）上实现了拆分。其中一种（CSP 1）基于（+）-（18-冠-6）-2,3,11,12-四羧酸，另外两种（CSP 2和CSP 3）基于（3,3'-二苯基-1,1'-联萘基）-20-冠-6。在硅胶表面含有残留硅烷醇基团保护正辛基的CSP 1和CSP 3上，美西律的拆分度（R(S)）大于1.00，但在CSP 2上拆分度（R(S)）小于1.00。在这三种CSP上拆分手性中心含有取代苯基的美西律类似物的色谱行为很大程度上取决于分析物的苯氧基。也就是说，含有2,6-二甲基苯氧基、3,4-二甲基苯氧基、3-甲基苯氧基、4-甲基苯氧基和简单苯氧基的美西律类似物在这三种CSP上都能很好地拆分，尽管手性识别效率因CSP而异。然而，含有2-甲基苯氧基的美西律类似物根本无法拆分或只能轻微拆分。在这三种CSP中，发现CSP 3在拆分美西律及其类似物方面表现出最高的手性识别效率，尤其是在拆分度（R(S)）方面。
