Institute for Research in Biomedicine Barcelona, Parc Cientific de Barcelona, Baldiri Reixac 10, E-08028 Barcelona, Spain.
J Chromatogr A. 2010 Feb 19;1217(8):1183-90. doi: 10.1016/j.chroma.2009.12.023. Epub 2009 Dec 18.
The racemic compound (+/-)-N-(3,4-cis-3-decyl-1,2,3,4-tetrahydrophenanthren-4-yl)-3,5-dinitrobenzamide ((+/-)-1), an analogue of increased lipophilicity of the chiral selector (CS) contained in the Whelk-O HPLC chiral stationary phase (CSP) has been resolved into its enantiomers by applying centrifugal partition chromatography (CPC). Considering the known enantioselectivity of the Whelk-O CS for naproxen, and the reciprocity concept in enantioseparation, (S)-naproxen related compounds were tested as CSs. In the search for an adequate solvent system, the partition behaviour of the two solutes, CS and racemate, has been studied using several biphasic solvent mixtures. The optimal CS concentration and sample loading capacity were determined in the chosen solvent system. The search for an appropriate CS and solvent system, the scale-up and optimization of the enantiomer separation by CPC, as well as the rationale for the unexpected elution order of enantiomers, are here described. The comparison of the preparative CPC separation achieved with that in HPLC, using a CSP containing an analogous CS, resulted favourable to the former in terms of loading capacity, solvent consumption and throughput.
外消旋化合物（±）-N-（3,4-顺-3-癸基-1,2,3,4-四氢菲-4-基）-3,5-二硝基苯甲酰胺（（±）-1）是手性选择剂（CS）亲脂性增加的类似物，该 CS 存在于 Whelk-O HPLC 手性固定相（CSP）中，通过应用离心分配色谱（CPC）将其对映异构体拆分。考虑到 Whelk-O CS 对萘普生的已知对映选择性，以及对映体分离中的相互作用概念，测试了（S）-萘普生相关化合物作为 CS。在寻找合适的溶剂系统时，使用几种双相溶剂混合物研究了两种溶质 CS 和外消旋体的分配行为。在所选溶剂系统中确定了最佳 CS 浓度和样品负载容量。对合适 CS 和溶剂系统的寻找、通过 CPC 对映体分离的放大和优化，以及对外消旋体出人意料的洗脱顺序的基本原理进行了描述。通过与使用类似 CS 的 CSP 进行的 HPLC 制备性 CPC 分离进行比较，就负载容量、溶剂消耗和通量而言，前者更有利。
