New Approaches to Catalyst Screening and Development

在化学系化学催化计划的资助下，内布拉斯加州大学林肯分校的大卫·伯科维茨博士正在开发新的反应，以帮助工业和制药部门以及学术界的化学家。目标分子在药物发现和新材料合成中有应用。他和他的团队探索的反应结合了生物学的各个方面，以获得关于反应速度的信息。这些反应还结合了生物学来制造大量特定的产品。伯科维茨博士积极参与促进学生参与科学、技术、工程和数学(STEM)学科的外展活动。这些活动包括在伯科维茨博士的实验室进行本科生研究实习，向来自四个州的高中生及其家长做开放演讲，让学生在教育发展的早期接触到STEM研究。Berkowitz和他的同事开发了一种催化剂筛选过程，称为原位酶筛选(ISES)。该方法利用“报告酶”为一组感兴趣的平行有机/有机金属反应提供有关相对速率、立体选择性和底物范围的实时信息。伯科维茨博士正在研究与镍的第一个催化不对称烯丙基胺化反应，以及有望从β-蒎烯和beta-D-(carba)fructopyranose-derived-1，2-diamines.衍生的新的手性Salen配体一种新的形式硫氰化/碳环化转化被发现，并被应用于构建面向多样性合成(DOS)的密集官能化和多环文库。通过开发替代光谱读出和筛选阵列来解决吞吐量问题。温度变化正在通过引入嗜热“报告酶”来发展“热-ISES”而被扩大。新的过渡金属-配体组合被探索用于合成化学家、药物化学家和化学生物学家感兴趣的四元、β、伽马不饱和氨基酸目标的立体控制结构。为了支持该项目的更广泛影响，伯科维茨博士在他的实验室里指导女学生和传统上不受重视的群体的成员。学生在化学/生物界面上接受的跨学科培训包括大量接触光谱学和动力学。这些技能为这些学生在现代工业和学术化学环境中的职业生涯做好了准备。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With funding from the Chemical Catalysis Program of the Division of Chemistry, Dr. David Berkowitz of the University of Nebraska-Lincoln is developing new reactions to help chemists in the industrial and pharmaceutical sectors and in academia. The target molecules have applications in drug discovery and the synthesis of new materials. The reactions that he and his team explore incorporate aspects of biology to get information on how fast reactions are going. These reactions also incorporate biology to make a large array of specific products. Dr. Berkowitz is actively engaged in outreach activities that promote the engagement of students in science, technology, engineering and mathematics (STEM) disciplines. These activities, which include undergraduate research internships in Dr. Berkowitz's laboratory, and open house presentations to high school students and their parents from a four-state area, are exposing students to STEM research early in their educational development.Dr. Berkowitz and co-workers develop a catalyst screening process, termed In Situ Enzymatic Screening (ISES). The method utilizes "reporting enzymes" to provide real time information on relative rate, stereoselectivity and substrate scope for a set of parallel organic/organometallic reactions of interest. Dr. Berkowitz is studying the first catalytic asymmetric allylic amination reaction with Ni and promising new chiral salen ligands that derive from beta-pinene- and beta-D-(carba)fructopyranose-derived-1,2-diamines. A promising new formal thiocyanopalladation/carbocyclization transformation has been discovered and is being applied to the construction of densely functionalized and polycyclic libraries for diversity-oriented synthesis (DOS). Throughput is addressed with the development of alternative spectroscopic read-outs and screening arrays. Temperature variation is being expanded via the development of "thermal-ISES" through the introduction of thermophilic "reporting enzymes." New transition metal-ligand combinations are explored toward the stereocontrolled construction of quaternary, beta,gamma-unsaturated amino acid targets of interest to synthetic chemists, medicinal chemists, and chemical biologists. In support of the broader impacts of the project, Dr. Berkowitz mentors female students and members of traditionally underreperesented groups in his laboratory. The interdisciplinary training that students receive at the chemistry/biology interface includes significant exposure to spectroscopy and kinetics. These skills is equiping these students for careers in both modern industrial and academic chemistry settings.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.