DEVELOPMENT OF MORE EFFICIENT CHIRAL 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收、激活和/或降解。在某些情况下，给定药物的两种外消旋物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。快速获取合理数量的手性材料以评估其药物活性是许多制药公司非常需要的。在分析和分离旋光性化合物的不对称技术中，手性固定相直接分离对映体的高效液相色谱技术一直是研究的热点。因此，各种各样的手性固定相被开发出来。虽然对目前所有的手性色谱柱进行全面的评估是不可能的，但常用的手性色谱柱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手性色谱固定相。具体地说，我们提出了组合库方法来开发手性固定相。这些方法将应用于开发有效的手性固定相，用于分离几种具有药物重要性的化合物的外消旋物。本文还将研究与硅胶手性固定相表征相关的化学反应。

As many enzymes and cell surface receptors possess handedness, the enantiomers of a racemic pair of compounds may be absorbed, activated, and/or degraded in different manners. In some instances, two racemates of a given 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 chiral 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 chiral stationary phases has been a subject of intense investigation. As a result, a wide variety of chiral stationary phases have been developed. Although a thorough evaluation of all the current chiral columns is impossible, the commonly used chiral columns do seem to have their limitations. It is fair to say that the chiral resolution of racemic materials remains a major challenge. This proposal is intended for the rapid development of more efficient stationary phases for chiral chromatography. Specifically, combinatorial library approaches are proposed for the development of chiral stationary phases. These methods will be applied to develop efficient chiral stationary phases for separating racemates of several compounds of pharmaceutical importance. The chemistry associated with the characterization of chiral stationary phases on silica gel will also be studied.