Koppenhoefer B, Zhu X, Jakob A, Wuerthner S, Lin B
Institute of Organic Chemistry, University of Tübingen, Germany.
J Chromatogr A. 2000 Apr 14;875(1-2):135-61. doi: 10.1016/s0021-9673(99)01210-8.
This is a selected review, highlighting our results obtained in an extended screening program ("The German-Chinese Drug Screening Program"), with a focus on a set of original data obtained with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TM-beta-CD) as the chiral solvating agent (CSA). The enantioseparation of 86 drugs by capillary zone electrophoresis in the presence of this CSA was successful for 47 drugs. The migration separation factors (alpham) and the migration retardation factors (Rm) were compared with those found for native beta-cyclodextrin (beta-CD). The patterns thus obtained were also compared with those observed for hexakis(2,3,6-tri-O-methyl)-alpha-CD (TM-alpha-CD) and octakis(2,3,6-tri-O-methyl)-gamma-CD (TM-gamma-CD), respectively. From the statistical data, it can be concluded that there is a remarkable influence of the analyte structure on the electrophoretic data. A substructure 4H was found in the analyte structure that has a significant influence on the analytes' behaviour. Thus, analytes bearing the substructure 4H do not only have a strong affinity to the CDs but also a high rate of success of chiral separation in all systems reviewed. In light of this, the different ring sizes of native cyclodextrins (alpha-, beta- and gamma-CD) readily explain their behaviour towards a limited test set of chiral drugs. Sterical considerations point to the significance of side-on-binding versus inclusion in the cavity of the host. In addition to the findings from the screening program, numerous references to the literature are given.
这是一篇综述，重点介绍了我们在一个扩展筛选项目（“德中药物筛选项目”）中取得的成果，该成果集中于以七（2,3,6-三-O-甲基）-β-环糊精（TM-β-CD）作为手性溶剂化剂（CSA）获得的一组原始数据。在该CSA存在下，通过毛细管区带电泳对86种药物进行对映体拆分，其中47种药物成功拆分。将迁移分离因子（αm）和迁移阻滞因子（Rm）与天然β-环糊精（β-CD）的相应因子进行了比较。由此获得的模式还分别与六（2,3,6-三-O-甲基）-α-环糊精（TM-α-CD）和八（2,3,6-三-O-甲基）-γ-环糊精（TM-γ-CD）观察到的模式进行了比较。从统计数据可以得出结论，分析物结构对电泳数据有显著影响。在分析物结构中发现了一个子结构4H，它对分析物的行为有重大影响。因此，带有子结构4H的分析物不仅对环糊精有很强的亲和力，而且在所有综述的系统中手性拆分成功率都很高。据此，天然环糊精（α-、β-和γ-CD）不同的环大小很容易解释它们对手性药物有限测试集的行为。空间因素表明侧链结合与主体空腔内包合的重要性。除了筛选项目的研究结果外，还给出了大量的文献参考。
