DEVELOPMENT OF MORE EFFICIENT CHIRAL STATIONARY PHASES

由于许多酶和细胞表面受体具有利手性，一对外消旋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，一种药物的两个外消旋体可能具有不同的甚至相反的药理活性。这一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大宗光学活性化合物的需求。对于许多制药公司来说，快速获得合理数量的手性材料以评估其药物活性是非常必要的。在发展起来的分析和分离光学活性化合物的不对称技术中，手性固定相液相色谱直接拆分对映体一直是人们研究的热点。因此，各种手性固定相应运而生。虽然不可能对目前所有的手性柱进行彻底的评估，但常用的手性柱似乎确实有其局限性。公平地说，外消旋材料的手性拆分仍然是一个主要的挑战。这一建议是为了快速开发更有效的手性色谱固定相。具体地说，提出了用于手性固定相开发的组合库方法。这些方法将被应用于开发高效的手性固定相，用于分离几种具有重要药用价值的化合物的外消旋。还将研究与硅胶上手性固定相表征相关的化学。

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.