Enantioselective stationary phases

对映选择性固定相

• 批准号: 6520570
• 负责人: Tingyu Li
• 金额: $ 21.56万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6520570
• 关键词: bioengineering /biomedical engineering; biomedical automation; biomimetics; chemical registry /resource; chemical structure function; circular magnetic dichroism; combinatorial chemistry; enzymes; high performance liquid chromatography; high throughput technology; peptide chemical synthesis; peptide library; pharmacology; polarimetry; protein purification; stereochemistry; stereoisomer; technology /technique development; ultraviolet spectrometry

As many enzymes and cell surface receptors possess handedness, the enantiomers of a racemic pair of compounds may be adsorbed, activated, and/or degraded in different manners. In some instances, two enantiomers of a given racemic 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 enantiomerically pure 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 enantioselective stationary phases has been a subject of intense investigation. As a result, a wide variety of enantioselective stationary phases have been developed. Although a thorough evaluation of all the current enantioselective columns is impossible, the commonly used ones do seem to have their limitations. It is fair to say that the chiral resolution of racemic materials remains a major challenge. This proposal in intended for the rapid development of more efficient stationary phases for enantioselective chromatography. Specifically, parallel combinatorial libraries are proposed for the development of enantioselective stationary phases. These methods will be applied to develop efficient enantoselective stationary phases for separating racemates of several compounds of pharmaceutical importance.

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附，激活和/或降解一对外消旋化合物的对映异构体。 在某些情况下，给定的外星人药物的两个对映异构体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，快速获取合理数量的对映体纯材料来评估其药物活动是非常需要的。在为分析和单独的光学活性化合物开发的不对称技术中，HPLC在对映选择性固定相上直接分离对映体的对照组一直是一项激烈研究的主题。 结果，已经开发了各种各样的对映选择性固定相。 尽管不可能对所有当前的对映选择柱进行彻底评估，但常用的对映射列似乎确实有其局限性。 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。该提案旨在快速开发更有效的固定相，用于对映选择色谱法。具体而言，提出了平行的组合文库，以开发对映选择性固定相。 这些方法将用于开发有效的对映选择性固定相，以分离几种药物重要性化合物的种族。