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、香料、香料和营养素，都是手性的，而今天超过50%的S畅销药物是作为单一对映体出售的。随着对映体化合物需求的增加，不对称合成技术也取得了长足的进步，这就需要发展分析技术来快速准确地确定手性化合物的立体化学纯度和完整性。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，可用于确定多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途径。这些传感器的独特设计便于根据紫外线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了几个有吸引力的功能的传感分析：(1)快速确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精确值，且重复性高；(3)将不再需要费力的底物衍生化；以及(4)使用经济高效和灵敏的技术(紫外或荧光光谱)将大大减少所需的传感器和分析物的数量。基于上述对映体选择性分析的意义，预计拟议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群体的几名学生将参与这一项目，并获得在立体化学、合成化学、立体选择性识别和手性拆分方面的丰富经验。这将为在制药、食品和农化行业工作的下一代化学家提供肥沃的培训场地。

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.