CAREER: Combinatorial Development of the Catalytic Asymmetric Aldol-Tishchenko Reaction

职业：催化不对称羟醛-季先科反应的组合开发

• 批准号: 9875488
• 负责人: James Morken
• 金额: $ 35万
• 依托单位: University of North Carolina at Chapel Hill
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-15 至 2004-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9875488&HistoricalAwards=false
• 关键词: CAREER; Combinatorial; Development; Catalytic; Asymmetric

Professor Morken is studying the sequential Aldol-Tischenko reaction that has been found to undergo catalysis by lithium alkoxides. A variety of chiral lithium alkoxides as well as alkoxides of other metals such as magnesium will be tested for their ability to catalyze the reaction while imparting control over its absolute stereochemistry. In order to simultaneously assess the reactivity of large numbers of catalysts, a thermographic screening technique will be employed. Since the Aldol-Tischenko reaction sequence has the potential to create a single 1,3-diol monoester from three different component aldehydes or ketones, a synthesis of the anticancer agent epithilone will be attempted. The key three-component assembly of the formal target molecule will create two asymmetric centers, a new C-C bond, and the ester functionality of the incipient macrolactone. Professor Morken's teaching focus is on the introduction of a multidisciplinary approach to scientific problem-solving. This will occur primarily in the laboratory portion of introductory chemistry courses, starting with sophomore honors organic students. The experimental focus will be the use of combinatorial synthesis for the preparation of Diels-Alder adducts that will be characterized using simple biochemical screens.With this CAREER award, the Synthetic Organic Program supports the teaching and research activities of Dr. James P. Morken of the University of North Carolina, Chapel Hill. The research aspect of these activities involves the combination of two or three molecules into a single unit while controlling its ultimate stereochemistry (three-dimensional structure). A specific anticancer compound, epithilone, is targeted as a demonstration of the power of this method to rapidly assemble a complex molecule from simpler component parts. Professor Morken's teaching efforts emphasize a multidisciplinary approach to the undergraduate teaching laboratory where combinatorial chemistry will be used as a vehicle for discovery-based learning. Students will carry out reactions on solid supports and use a number of techniques to characterize their products, which will include some that are known to be active in biochemical assays.

Morken教授正在研究连续的aldoll - tischenko反应，该反应被发现可以由锂烷氧化物催化。将测试各种手性锂烷氧化物以及其他金属（如镁）的烷氧化物在催化反应的同时控制其绝对立体化学的能力。为了同时评价大量催化剂的反应性，将采用热成像筛选技术。由于Aldol-Tischenko反应序列有可能从三种不同的醛或酮成分中产生单一的1,3-二醇单酯，因此将尝试合成抗癌剂上皮酮。正式目标分子的关键三组分组装将产生两个不对称中心，一个新的C-C键和早期大内酯的酯功能。Morken教授的教学重点是引入多学科方法来解决科学问题。这将主要发生在化学导论课程的实验部分，从大二荣誉有机学生开始。实验重点将是使用组合合成方法制备Diels-Alder加合物，该加合物将使用简单的生化筛选进行表征。有了这个职业奖，合成有机项目支持北卡罗来纳大学教堂山分校的詹姆斯·p·莫肯博士的教学和研究活动。这些活动的研究方面包括将两个或三个分子结合成一个单元，同时控制其最终的立体化学（三维结构）。一种特殊的抗癌化合物，上皮酮，被作为该方法的目标，以证明该方法可以从简单的组成部分快速组装成复杂的分子。Morken教授的教学工作强调在本科教学实验室中采用多学科方法，组合化学将被用作基于发现的学习工具。学生们将在固体载体上进行反应，并使用多种技术来表征他们的产物，其中包括一些已知在生化分析中具有活性的技术。