DEVELOPMENT OF MORE EFFICIENT CHIRAL STATIONARY PHASES

开发更高效的手性固定相

• 批准号: 6856994
• 负责人: Tingyu Li
• 金额: $ 4.9万
• 依托单位: MISSISSIPPI STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6856994
• 关键词: combinatorial chemistry; physical separation; stereochemistry; technology /technique development

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.

由于许多酶和细胞表面受体具有惯用性，因此可以以不同的方式吸收，激活和/或降解的一对外消旋化合物的对映异构体。 在某些情况下，给定药物的两个种族可能具有不同甚至相反的药理学活动。 与制药行业中其他因素结合的这一方面刺激了对映体纯中间体和散装光学活性化合物的需求。 对于许多制药公司来说，非常需要快速获取合理数量的手性材料来评估其药物活动。在为分析和分离光学活性化合物开发的不对称技术中，HPLC在手性固定相上直接分离对映异构体一直是一项激烈研究的主题。 结果，已经开发了多种手性固定相。尽管不可能对所有当前的手性柱进行彻底评估，但通常使用的手性柱确实有其局限性。可以公平地说，外消旋材料的手性解决仍然是一个重大挑战。该建议旨在快速开发用于手性色谱法的更有效的固定相。具体而言，提出了组合图书馆方法来发展手性固定相。 这些方法将用于开发有效的手性固定相，以分离几种药物重要性化合物的种族。 还将研究与二氧化硅凝胶上手性固定相的表征相关的化学因素。