Enantioselective stationary phases

由于许多酶和细胞表面受体具有手性，外消旋对化合物的对映体可能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个对映体可能具有不同甚至相反的药理活性。这方面与制药行业内的其他因素一起刺激了对对映体纯中间体和散装光学活性化合物的需求。对许多制药公司来说，快速获得合理数量的对映体纯材料以评估其药物活性是非常可取的。在分析和分离旋光性化合物的不对称技术中，利用高效液相色谱在对映体选择固定相上直接分离对映体一直是研究的热点。因此，各种各样的对映选择性固定相被开发出来。尽管对当前所有的对映体选择列进行全面的评估是不可能的，但常用的列似乎确实有其局限性。公平地说，外消旋体材料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选择色谱固定相。具体地说，并行组合库被提出用于开发对映选择性固定相。这些方法将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物意义的化合物的外消旋物。

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.