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教授正在研究依次的藻静脉反应，该反应已被发现通过烷氧化锂进行催化。 各种手性锂烷氧化物以及其他金属（例如镁）的烷氧化物将用于催化反应的能力，同时控制其绝对立体化学。 为了同时评估大量催化剂的反应性，将采用热力计筛选技术。 由于醛醇 - 静脉反应序列具有从三种不同的成分醛或酮产生单个1,3-二醇单酯的潜力，因此将尝试尝试抗癌剂上皮酮的合成。 正式目标分子的关键三组分组件将创建两个不对称中心，一个新的C-C键和初始大分子的酯功能。 莫肯教授的教学重点是引入一种多学科的科学问题解决方法。 这将主要发生在化学入门课程的实验室部分，从大二学生荣誉有机学生开始。 实验重点将是使用组合合成来制备Diels-Alder加合物，这些加合物将使用简单的生化筛选来表征。在此职业奖中，合成有机计划支持詹姆斯·P·Morken博士的教学和研究活动。北卡罗来纳大学教堂山。 这些活动的研究方面涉及将两个或三个分子组合为一个单元，同时控制其最终立体化学（三维结构）。 特定的抗癌化合物上皮酮的靶向是该方法快速从较简单的部分中快速组装复杂分子的能力。 Morken教授的教学工作强调了本科教学实验室的多学科方法，其中组合化学将用作基于发现的学习工具。 学生将对稳固的支持进行反应，并使用许多技术来表征其产品，其中包括一些已知在生化测定中活跃的产品。