Discovery Chemistry Department, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
J Chromatogr A. 2013 Aug 30;1305:310-9. doi: 10.1016/j.chroma.2013.07.046. Epub 2013 Jul 17.
A rapid screening method to identify the best conditions for chiral separations is described. We analyzed a representative set of 80 racemic compounds against 25 different chiral stationary phases with three different mobile phases to identify the combination of columns and mobile phases that will separate the most compounds on the initial screen. While the OD separated the largest number of compounds, we found the best combination of six columns to be the AD, AS, AY, CC4, ID and Whelk-O1. The second team included the CCC, Cellulose-1, Cellulose-3 or OJ, IA, IE and IF. All 80 compounds were separated with a resolution range of 0.65-15.36. Screening the covalently bonded phases provided separation for 79 of the 80 compounds. We also found ethanol (0.1% NH4OH) separated more compounds than methanol (0.1% NH4OH) or isopropanol (0.1% NH4OH). As part of this study, we also compared the effectiveness of stationary phases that have the same chiral selector. Finally, we demonstrated the effectiveness of using a fast, 1.5-min screening method that utilizes a 1.7μm coated polysaccharide chiral stationary phase.
描述了一种快速筛选方法,用于确定手性分离的最佳条件。我们分析了一组具有代表性的 80 个外消旋化合物,使用三种不同的流动相分析了 25 种不同的手性固定相,以确定在初始筛选中分离最多化合物的柱和流动相组合。虽然 OD 分离了最多数量的化合物,但我们发现最佳的六根柱组合为 AD、AS、AY、CC4、ID 和 Whelk-O1。第二组包括 CCC、Cellulose-1、Cellulose-3 或 OJ、IA、IE 和 IF。所有 80 种化合物都得到了分离,分辨率范围为 0.65-15.36。筛选共价键合相为 80 种化合物中的 79 种提供了分离。我们还发现乙醇(0.1%NH4OH)比甲醇(0.1%NH4OH)或异丙醇(0.1%NH4OH)分离更多的化合物。作为这项研究的一部分,我们还比较了具有相同手性选择器的固定相的有效性。最后,我们展示了使用快速、1.5 分钟筛选方法的有效性,该方法利用 1.7μm 涂层多糖手性固定相。