DEVELOPMENT OF MORE EFFICIENT CHIRAL 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收、活化和/或降解。 在某些情况下，给定药物的两种外消旋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。 快速获得合理量的手性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，在手性固定相上通过HPLC直接分离对映体一直是研究的热点。 因此，各种各样的手性固定相已被开发出来。虽然对目前所有的手性柱进行全面的评价是不可能的，但常用的手性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手性色谱固定相。具体而言，组合库方法提出了手性固定相的发展。 这些方法将被应用于开发高效的手性固定相，用于分离几种重要的药物化合物的外消旋体。 与硅胶上的手性固定相的表征相关的化学也将被研究。

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.