Liquid chromatography enantiomeric separation of chiral ethanolamine substituted compounds
Liquid chromatography enantiomeric separation of chiral ethanolamine substituted compounds
复制标题
手性乙醇胺取代化合物的液相色谱对映体分离
DOI：
10.1002/chir.23419
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发表时间：
2022
期刊：
影响因子：
2
通讯作者：
Armstrong, Daniel W.
中科院分区：
文献类型：
--
作者：
Firooz, Sepideh Khaki;Putman, Joshua;Fulton, Brandon;Lovely, Carl J.;Berthod, Alain;Armstrong, Daniel W.
合成了11种外消旋乙醇胺衍生物，并采用液相色谱法在不同手性柱上对它们的对映体进行了分离。这些衍生物包括手性邻氨基醇、β-羟基脲、β-羟基硫脲和β-羟基胍，所有这些都存在于许多活性药物成分中。筛选研究进行了6个手性固定相包含柱，包括最近推出的表面多孔颗粒键合两个大环糖肽，环糊精衍生物和cyclofructan衍生物。剩下的两个柱含有手性固定相，基于纤维素衍生物或衍生的直链淀粉，两者都结合到完全多孔的颗粒上。环糊精和纤维素基手性固定相被证明是最广泛有效的选择剂，能够分别分离11种测试化合物中的8种和7种。关于分析物的结构特征，显着的差异，在对映体识别观察到的化合物之间含有苯基和环己基邻近的立体中心。此外，用较大且电负性较小的硫原子取代小的电负性氧原子，会导致纤维素衍生物和基于万古霉素的手性选择剂的手性识别产生显着差异。
Eleven racemic ethanolamine derivatives were prepared, and their enantiomers were separated using liquid chromatography with various chiral columns. These derivatives included chiral vicinal amino alcohols, β‐hydroxy ureas, β‐hydroxy thioureas, and β‐hydroxy guanidines, all of which are present in many active pharmaceutical ingredients. The screening study was performed with six chiral stationary phase containing columns, including four recently introduced superficially porous particles bonded with two macrocyclic glycopeptides, a cyclodextrin derivative and a cyclofructan derivative. The two remaining columns contained chiral stationary phases, based on either a cellulose derivative or derivatized amylose, both bonded to fully porous particles. The cyclodextrin and cellulose‐based chiral stationary phases proved to be the most broadly effective selectors and were able to separate 8 and 7 of the 11 tested compounds, respectively. With respect to analyte structural features, marked differences in enantiorecognition were observed between compounds containing phenyl and cyclohexyl groups adjacent to the stereogenic center. Additionally, replacing a small electronegative oxygen atom by a larger and less electronegative sulfur atom induced a significant difference in chiral recognition by the cellulose derivative as well as by the vancomycin‐based chiral selectors.