New Approaches to Catalyst Screening and Development

催化剂筛选和开发的新方法

• 批准号: 1214019
• 负责人: Stephen DiMagno
• 金额: $ 46.5万
• 依托单位: University of Nebraska-Lincoln
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1214019&HistoricalAwards=false
• 关键词: New; Approaches; Catalyst; Screening; Development

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.

技术摘要：国家科学基金会凭借该奖项资助内布拉斯加大学在 Stephen G. DiMagno 教授（代替 David Berkowitz 教授的 PI）的指导下进行研究，开发基于酶的催化剂筛选新方法。 该方法涉及使用与被筛选的有机/有机金属催化剂串联操作的酶报告酶，前者在水性报告层中，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选择性，因此被称为“原位酶筛选”(ISES)。 这里特别关注新的筛选酶/条件的鉴定，这些酶/条件将允许实验人员检查新的离去基团和新的转化，并从环境温度转移到高温。 目标转化包括生物有机和药物化学家特别感兴趣的转化，例如作为潜在的基于机制的酶抑制剂的对映体富集、季铵、α-乙烯基氨基酸的催化途径。非技术摘要：该研究项目本质上是跨学科的，处于有机化学和生物学之间的界面，利用大自然的催化剂来协助开发用于化学合成的有用的人造催化剂。 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。 该研究预计将对有机合成、绿色化学、生物催化和过程化学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活动接触高中生。