Oligoproline chiral selectors and their applications

描述（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以以不同的方式被它们吸收、活化和降解。由于这种现象，在许多情况下，外消旋药物的两种对映异构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导方针。从那时起，药物越来越多地作为纯对映体销售。为了开发这种对映体纯的药物，对手性分离技术的需求很高。它们用于分析分离以确定分析物的对映体纯度。它们也被广泛用作快速获得合理量的对映体纯材料的有效方法，以评估其在药物开发中的药物活性。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。尽管不可能对当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存在一些局限性。公平地说，外消旋物质的手性拆分仍然是一个重大挑战。本AREA提案旨在继续PI开发高效手性色谱固定相的努力。具体目标包括进一步改进寡脯氨酸手性选择剂，新型寡脯氨酸手性固定相，以及脯氨酸手性选择剂在其他分离方法中的应用。 如果该提案的目标能够成功实现，就可以很容易地获得对映体纯的化合物。这些化合物在药物开发中非常重要，因为许多药物要么以对映体纯的形式商业化，要么从对映体纯的化合物开发。

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.