New Approaches to Catalyst Screening and Development

技术概述：美国国家科学基金会将资助内布拉斯加大学在Stephen G. DiMagno教授（代替David Berkowitz教授）指导下的研究，以开发新的基于酶的催化剂筛选方法。这种方法涉及使用酶报告酶与被筛选的有机/有机金属催化剂串联工作，前者在水报告层中，后者在同一容器内的有机溶剂层中。这种安排允许实时评估关键变量，包括相对反应速率和对映体选择性，因此被称为“原位酶筛选”（ISES）。这里特别关注的是确定新的筛选酶/条件，这将允许实验人员检查新的离开基团和新的转化，并从环境温度转移到高温。转化的目标包括那些生物有机和药物化学家特别感兴趣的转化，例如催化途径到对映体富集，季，α -乙烯基氨基酸作为潜在的基于机制的酶抑制剂。非技术总结：本研究项目本质上是跨学科的，处于有机化学和生物学的界面，因为自然界的催化剂被用来协助开发有用的人造化学合成催化剂。从事该项目的科学家将获得一线不对称催化剂开发和现代制备酶学的实践经验。该研究有望在有机合成、绿色化学、生物催化和过程化学等领域产生更广泛的科学影响。PI将继续为博士后、研究生和本科生提供跨学科培训，该小组将继续通过化学日与高中生接触。

TECHNICAL SUMMARY:With this award the National Science Foundation is funding studies at the University of Nebraska, under the direction of Professor Stephen G. DiMagno (substitute PI for Professor David Berkowitz), to develop new enzyme-based methods for catalyst screening. This approach involves the use of enzymatic reporting enzymes operating in tandem with the organic/organometallic catalysts being screened, with the former in an aqueous reporting layer, and the latter in an organic solvent layer within the same vessel. This arrangement permits for the assessment of key variables including relative reaction rate and enantioselectivity, in real time, and is thus termed "In Situ Enzymatic Screening" (ISES). Particular focus here is on the identification of new screening enzymes/conditions that will permit the experimentalist to examine new leaving groups and new transformations and to move from ambient to elevated temperatures. Transformations being targeted include those of particular interest to bioorganic and medicinal chemists, such as catalytic routes to enantio-enriched, quaternary, alpha-vinyl amino acids as potential mechanism-based enzyme inhibitors.NON-TECHNICAL SUMMARY:This research project is inherently interdisciplinary, at the interface between organic chemistry and biology, as Nature's catalysts are exploited to assist with the development of useful human-made catalysts for chemical synthesis. Scientists working on the project will gain hands-on experience with both frontline asymmetric catalyst development and with modern preparative enzymology. The research is expected to have broader scientific impact on the areas of organic synthesis, green chemistry, biocatalysis, and process chemistry. The PI will continue to provide cross-disciplinary training to postdocs, graduate, and undergraduate students, and the group will continue to reach out to high school students through Chemistry Day.