Enantioselective stationary phases

由于许多酶和细胞表面受体具有手性，因此外消旋化合物对的对映异构体可以以不同的方式被吸附、活化和/或降解。 在某些情况下，给定外消旋药物的两种对映异构体可能具有不同或甚至相反的药理学活性。 这一方面与制药工业中的其他因素一起刺激了对映体纯中间体和散装光学活性化合物的需求。 快速获得合理量的对映体纯材料以评估其药物活性是许多制药公司高度期望的。在用于分析和分离光学活性化合物的不对称技术中，通过HPLC在对映选择性固定相上直接分离对映体一直是研究的热点。 因此，各种各样的对映体选择性固定相已被开发出来。 虽然对目前所有的对映选择性色谱柱进行全面的评价是不可能的，但常用的色谱柱似乎确实有其局限性。 公平地说，外消旋物质的手性拆分仍然是一个重大挑战。该建议旨在快速开发更有效的对映体选择性色谱固定相。具体而言，平行组合库提出了发展的对映体选择性固定相。 这些方法将被应用于开发有效的对映体选择性固定相，用于分离几种具有重要药用价值的化合物的外消旋体。

As many enzymes and cell surface receptors possess handedness, the enantiomers of a racemic pair of compounds may be adsorbed, activated, and/or degraded in different manners. In some instances, two enantiomers of a given racemic drug may have different or even opposite pharmacological activities. This aspect in conjunction with other factors within the pharmaceutical industry have stimulated the need for enantiomerically pure intermediates and bulk optically active compounds. Quick access to reasonable amounts of enantiomerically pure materials to assess their pharmaceutical activity is highly desirable to many pharmaceutical companies. Among the asymmetric technologies developed to analyze and separate optically active compounds, the direct separation of enantiomers by HPLC on enantioselective stationary phases has been a subject of intense investigation. As a result, a wide variety of enantioselective stationary phases have been developed. Although a thorough evaluation of all the current enantioselective columns is impossible, the commonly used ones do seem to have their limitations. It is fair to say that the chiral resolution of racemic materials remains a major challenge. This proposal in intended for the rapid development of more efficient stationary phases for enantioselective chromatography. Specifically, parallel combinatorial libraries are proposed for the development of enantioselective stationary phases. These methods will be applied to develop efficient enantoselective stationary phases for separating racemates of several compounds of pharmaceutical importance.