DESIGNING ATROPISOMERIC SENSORS FOR ENANTIOSELECTIVE RECOGNITION OF CHIRAL COMPOUNDS

许多具有生物活性的化合物，包括药物、农用化学品、调味品、香料和营养素，都是手性的，今天超过50%的手性化合物都是手性的。美国最畅销的药物都是以单一对映体的形式销售的。对映体纯化学品的需求不断增加，伴随着不对称合成的重大进展，这需要开发快速准确测定手性化合物的立体化学纯度和完整性的分析技术。目前药物发现的瓶颈是分析这些反应混合物的对映体组成和产率。因此，Wolf小组将开发新的传感器，可用于测定各种化合物的对映体纯度和总浓度，从而为快速筛选反应混合物和手性化合物库提供新的入口。这些传感器的独特设计有助于基于紫外和荧光光谱或其他光学方法区分对映体。该小组将开发和测试结合联合收割机几个有吸引力的特点的传感分析：（1）快速测定未知混合物的浓度和对映体组成;（2）简单的光学测量将提供具有高重现性的准确值;（3）不需要费力的底物衍生化;以及（4）使用成本有效且灵敏的技术（UV或荧光光谱法）将大大减少所需的传感器和分析物的量。基于上述对映体选择性分析的重要性，预计该研究的基础和应用方面将使学术和工业化学家受益。来自科学界代表性不足的团体的几名学生将参加这个项目，并在立体化学，合成化学，立体选择性识别和手性拆分方面获得丰富的经验。这将为在制药、食品和农业化学工业工作的下一代化学家提供肥沃的培训基础。

Many biologically active compounds, including pharmaceuticals, agrochemicals, flavors, fragrances, and nutrients, are chiral, and more than 50% of today?s top-selling drugs are sold as single enantiomers. The increasing demand for enantiopure chemicals has been accompanied by significant progress in asymmetric synthesis, and it requires the development of analytical techniques for fast and accurate determination of the stereochemical purity and integrity of chiral compounds. The current bottleneck in drug discovery is to analyze the enantiomeric composition and yield of these reaction mixtures. The Wolf group will therefore develop new sensors that can be used to determine both the enantiomeric purity and the overall concentration of a wide range of compounds, thus providing a new entry to rapid screening of reaction mixtures and libraries of chiral compounds. The unique design of these sensors facilitates differentiation of enantiomers based on ultraviolet and fluorescence spectroscopy or other optical methods. The group will develop and test sensing assays that combine several attractive features: (1) fast determination of both concentration and enantiomeric composition of unknown mixtures; (2) simple optical measurements will provide accurate values with high reproducibility; (3) laborious substrate derivatization will become unnecessary; and (4) the use of cost-effective and sensitive techniques (UV or fluorescence spectroscopy) will greatly reduce the amount of sensor and analyte required. Based on the significance of enantioselective analysis outlined above, it is expected that the fundamental and applied aspects of the proposed research will benefit academic and industrial chemists alike. Several students from groups that are underrepresented in the sciences will participate in this project and receive extensive experience in stereochemistry, synthetic chemistry, stereoselective recognition and chiral resolution. This will provide fertile training grounds for the next generation of chemists working in the pharmaceutical, food and agrochemical industries.