Department of Analytical Chemistry, University of Vienna, Waehringer Strasse 38, 1090 Vienna, Austria.
J Chromatogr A. 2013 Oct 4;1310:56-65. doi: 10.1016/j.chroma.2013.08.019. Epub 2013 Aug 13.
In the present contribution we report a HPLC enantioseparation method for a library of amido-aminophosphonate structures generated by a novel Ugi-multicomponent reaction. The enantioseparation of these novel potentially bioactive molecules was achieved by means of HPLC on cinchona-carbamate based chiral anion-exchangers under polar organic elution conditions. The compounds were synthesized with the aim of offering a wide degree of heterogeneity in terms of structural elements to evaluate the influence of various structural motifs on enantioselectivity. The resultant compound library allows to derive structure-enantioselectivity relationships useful for understanding the chiral recognition process. As part of the study mobile phase characteristics such as concentration and type of counterion, mobile phase composition, apparent pH and temperature were investigated with regards to their effect on the separation performances. Employing a single mass spectrometry-compatible mobile phase, 23 compounds out of a pool of 42 racemic amido-aminophosphonate structures reached full baseline separation (Rs>1.5) and 5 were almost baseline separated (1<Rs<1.5). This result clearly demonstrates the wide applicability of carbamoylated-cinchona alkaloids as chiral stationary phases for this class of analytes.
在本研究中，我们报道了一种通过新型 Ugi 多组分反应生成的酰胺-氨基膦酸酯结构库的 HPLC 对映体拆分方法。通过在极性有机洗脱条件下使用基于辛可宁-氨基甲酸酯的手性阴离子交换剂在 HPLC 上实现了这些新型潜在生物活性分子的对映体拆分。这些化合物的合成旨在提供在结构元素方面具有高度异质性的程度，以评估各种结构基序对对映选择性的影响。所得的化合物库允许得出有用的结构-对映选择性关系，有助于理解手性识别过程。作为该研究的一部分，考察了流动相特性，例如浓度和抗衡离子的类型、流动相组成、表观 pH 值和温度，以研究它们对分离性能的影响。使用单一质谱兼容的流动相，在 42 个外消旋酰胺-氨基膦酸酯结构的池中共分离出 23 个化合物达到完全基线分离（Rs>1.5），5 个化合物几乎达到基线分离（1<Rs<1.5）。这一结果清楚地表明，辛可宁衍生的手性固定相可广泛应用于这类分析物的对映体拆分。
