Semmelweis University, Department of Pharmaceutical Chemistry, Budapest, H-1092 Hogyes Endre u. 9, Hungary.
J Pharm Biomed Anal. 2010 Dec 15;53(5):1258-66. doi: 10.1016/j.jpba.2010.07.032. Epub 2010 Jul 30.
In this work, the enantiomeric separation of three vinca alkaloid enantiomers (vincamine, vinpocetine and vincadifformine) has been investigated in an aqueous capillary electrophoresis (CE) system using cyclodextrins (CDs). The investigated CDs were the native alpha-, beta-, and gamma-CDs and their hydroxypropylated, randomly methylated, carboxymethylated and sulfobutylated derivatives. The first part of this study consisted of the determination of the apparent averaged complex stability constants with the selected CDs. Several parameters, such as the nature and the concentration of the CD, were studied and were found to have a significant effect on the enantiomeric resolution for all studied compounds. All three vinca alkaloids were successfully enantioseparated with CDs where different migration orders were observed in case of several CDs depending on the cavity size or substituent of the host. Chiral separation and determination of the stability constants were also performed with NMR spectroscopy which confirmed the CE results. Averaged stoichiometries of the complexes were determined using the Job plot method resulting in a 1:1 complex irrespective of the alkaloid enantiomers or cyclodextrin derivative. The structures of the inclusion complexes were elucidated using 2D ROESY NMR spectroscopy. On the basis of NMR results reversal of enantiomer migration order was clarified in various cases.
在这项工作中，使用环糊精（CDs）研究了水相毛细管电泳（CE）体系中三种长春生物碱对映体（长春胺、长春西汀和长春氟宁）的对映体分离。所研究的 CD 为天然的 α-、β-和 γ-CD 及其羟丙基化、随机甲基化、羧甲基化和磺丁基化衍生物。本研究的第一部分包括用选定的 CDs 测定表观平均配合物稳定常数。研究了几种参数，如 CD 的性质和浓度，发现它们对所有研究化合物的对映体分辨率都有显著影响。所有三种长春生物碱都成功地与 CD 对映体分离，在几种 CD 的情况下观察到不同的迁移顺序，这取决于主体的空腔大小或取代基。用 NMR 光谱法进行手性分离和稳定常数的测定，也证实了 CE 结果。使用 Job 图法确定了配合物的平均化学计量比，得到了 1:1 的配合物，与生物碱对映体或环糊精衍生物无关。使用 2D ROESY NMR 光谱法阐明了包合物的结构。根据 NMR 结果，在各种情况下阐明了对映体迁移顺序的反转。
