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

莫肯教授正在研究顺序的Aldol-Tischenko反应，已发现该反应经历了锂醇盐的催化。各种手性锂醇氧化物以及其他金属的醇氧化物，如镁，将被测试其催化反应的能力，同时给予其绝对立体化学控制。为了同时评估大量催化剂的反应活性，将采用热像筛选技术。由于Aldol-Tischenko反应序列有可能从三种不同成分的醛或酮生成单一的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，以及初始大内酯的酯功能。莫肯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入门课程的实验室部分，从大二的有机优等生开始。实验的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。有了这个职业奖，合成有机计划支持了北卡罗来纳大学教堂山分校的James P.Morken博士的教学和研究活动。这些活动的研究方面涉及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)。一种特定的抗癌化合物，上皮酮，被用作展示这种方法的力量，从较简单的组成部分快速组装复杂的分子。莫肯教授的教学努力强调了本科教学实验室的多学科方法，在那里组合化学将被用作基于发现的学习的工具。学生将在固体载体上进行反应，并使用一些技术来表征他们的产品，其中包括一些已知在生化分析中具有活性的产品。

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.