DEVELOPMENT OF LIGAND ASSISTED ASYMMETRIC SYNTHESES

描述：(首席调查员)多年来，有一个 非常重视有机化学中的不对称合成。在这 背景下，高效反应的发现和发展一直是 主要研究活动的舞台。这种新的合成物的有效性 传统上，进程的评估是通过它们在合成 自然界中发现的一系列有机分子。从合成的 对合成多种酶具有重要生物学意义的天然产物 抑制剂或受体激动剂或拮抗剂，对 对映体选择性键构筑的一般策略 立体可预测的时尚。此外，与日俱增的孤立和 多种具有重要生物活性的复杂天然产物的表征 功能以及对许多复杂人类的认识不断加深 分子水平上的疾病，要求开发更新的合成 方法论。分子结合的问题和概念， 结构-功能关系、反应性、分子间以及 分子内键相互作用都处于有机研究的前沿 化学反应。不对称合成现在面临着新的挑战和 机遇。很自然地，基础知识的扩展，发展 关于较新的不对称合成和对各种不对称的理解 分子水平上的反应具有巨大的意义。在这 背景，我的计划是设计和开发各种配体辅助 化学计量不对称合成和催化不对称合成 在合成天然和非天然有机分子方面的应用。这个 本提案的具体目标是：(A)深入执行 不对称酯烯醇醛缩合反应的机理研究 不对称催化杂Diels-Alder反应；(B)利用 获得进一步发展这些反应的分子洞察力以及 发现新的不对称过程；(C)展示这种 不对称反应在合成多种具有重要生物学意义的化合物中的应用 分子，如马杜霉素。除了广泛的范围和 总而言之，这一研究领域将提供极好的机会 在实验室教授和培训研究生和本科生。

DESCRIPTION: (Principal Investigator's) Over the years, there has been an enormous emphasis on asymmetric synthesis in organic chemistry. In this context, the discovery and development of efficient reactions has been the arena of major research activities. The effectiveness of such new synthetic processes is traditionally evaluated by their utility in the synthesis of an array of organic molecules that are found in nature. From synthesis of biologically important natural products to synthesis of various enzyme inhibitors or receptor agonists or antagonists, there is a growing need for general strategies for enantioselective bond construction in a stereopredictable fashion. In addition, the growing isolation and characterization of many complex natural products with important biological functions as well as the increasing understanding of many complex human diseases at the molecular level, demands the development of newer synthetic methodologies. The questions and concepts of molecular binding, structure-function relationship, reactivity, and intermolecular as well as intramolecular bonding interactions all are at the forefront of organic chemistry. Asymmetric synthesis is now faced with new challenges and opportunities. Quite naturally, expansion of basic knowledge, development of newer asymmetric synthesis and understanding of various asymmetric reactions at the molecular level are of enormous significance. In this context, my plan is to design and develop various ligand assisted stoichiometric and catalytic asymmetric syntheses and demonstrate their utility in the synthesis of natural and unnatural organic molecules. The specific aims of the present proposal are: (a) to perform in-depth mechanistic studies of asymmetric ester enolate aldol reactions and asymmetric catalytic hetero Diels-Alder reactions; (b) to utilize the obtained molecular insight to further develop these reactions as well as discover new asymmetric processes; (c) to demonstrate the utility of such asymmetric reactions in the synthesis of various biologically important molecules, such as madumycin. Besides the broad range of scope and generality, this line of research will provide excellent opportunities to teach and train graduate and undergraduate students in the laboratory.