DEVELOPMENT OF LIGAND ASSISTED ASYMMETRIC SYNTHESES

配体辅助不对称合成的开发

• 批准号: 6138561
• 负责人: ARUN K GHOSH
• 金额: $ 16.22万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6138561
• 关键词: Diels Alder reaction; aldehydes; antibiotics; chemical models; chemical synthesis; enolate; esters; model design /development; stereochemistry

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.

描述：（主要研究者）多年来， 有机化学中对不对称合成的极大重视。 在这 高效反应的发现和发展一直是 主要研究活动的竞技场。 这种新型合成药物的有效性 传统上通过它们在合成一种 自然界中发现的一系列有机分子。 的合成的 生物学上重要的天然产物对各种酶的合成 抑制剂或受体激动剂或拮抗剂，对 一般策略的对映选择性键的建设， 立体可预测的时尚 此外，日益孤立和 许多复杂的天然产物具有重要的生物学特性， 功能以及对许多复杂的人类 在分子水平上的疾病，需要开发新的合成 方法论。 分子结合的问题和概念， 结构-功能关系、反应性和分子间以及 分子内键合相互作用都是有机化学的前沿 化学. 不对称合成现在面临着新的挑战， 机会 很自然地，基础知识的扩展， 新的不对称合成和理解各种不对称 分子水平上的反应是非常重要的。 在这 在此背景下，我的计划是设计和开发各种配体辅助 化学计量和催化不对称合成，并证明其 在天然和非天然有机分子的合成中的用途。 的 本建议的具体目标是：（a）深入开展 不对称酯烯醇化物aldol反应的机理研究 不对称催化杂Diels-Alder反应;（B）利用 获得了分子洞察力，以进一步发展这些反应，以及 发现新的不对称过程;（c）证明这种方法的实用性 在合成各种生物重要的不对称反应 分子，如马杜霉素。 除了广泛的范围和 一般来说，这条研究路线将提供极好的机会， 在实验室中教授和培训研究生和本科生。