Oligoproline chiral selectors and their applications

描述（由申请人提供）：由于酶和其他生物受体具有手性中心，外消旋化合物的对映体可能以不同的方式被它们吸收、激活和降解。由于这种现象，在许多情况下，一种外消旋药物的两个对映体可能具有非常不同的药理活性。认识到手性在药物开发中的重要性，美国食品和药物管理局（FDA）于1992年发布了关于具有手性中心的药物的立体异构体的指南。从那时起，越来越多的药物以纯对映体的形式上市。为了开发这样的对映体纯药物，对手性分离技术的需求很大。在分析分离中需要它们来确定分析物的对映体纯度。它们也被广泛用于提供快速获取合理数量的对映体纯物质的有效方法，以便在药物开发中评估其药物活性。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一些局限性。公平地说，外消旋体材料的手性拆分仍然是一个重大挑战。本区域提案旨在继续PI的努力，以开发有效的手性色谱固定相。具体目标包括进一步改进低聚脯氨酸手性选择剂，开发新型低聚脯氨酸手性固定相，以及将脯氨酸手性选择剂应用于其他分离方法。

DESCRIPTION (provided by applicant): Since enzymes and other biological receptors possess chiral centers, enantiomers of a racemic compound may be absorbed, activated, and degraded by them in different manners. Due to this phenomenon, in many instances, two enantiomers of a racemic drug may have very different pharmacological activities. Recognizing the importance of chirality in drug development, the US Food and Drug Administration (FDA) issued guidelines in 1992 regarding the stereoisomers of drugs with chiral centers. Since then, drugs are increasingly marketed as pure enantiomers. To develop such enantiomerically pure drugs, techniques for chiral separations are in high demand. They are needed for analytic separations to determine the enantiomerical purity of analytes. They are also widely used as efficient methods to provide quick access to reasonable amounts of enantiomerically pure materials in order to assess their pharmaceutical activity in drug development. 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 some limitations. It is fair to say that the chiral resolution of racemic materials remains a major challenge. This AREA proposal is intended to continue the PI's efforts to develop efficient stationary phases for chiral chromatography. Specific aims include further improvement of the oligoproline chiral selectors, newer types of oligoproline chiral stationary phases, and the application of proline chiral selectors to other separation methods. If the aims of the proposal are successfully achieved, enantiomerically pure compounds could be made readily available. These compounds are very important in drug development, as many drugs are either commercialized in enantiomerically pure form or developed from enantiomerically pure compounds.