NEW METHODS FOR STEREOSELECTIVE ADDITIONS TO CARBONYLS

羰基立体选择性加成的新方法

• 批准号: 6519516
• 负责人: TAREK SAMMAKIA
• 金额: $ 23.13万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6519516
• 关键词: Diels Alder reaction; aldehydes; alkyl group; antifungal agents; carbonyl compound; catalyst; chemical addition; chemical synthesis; heterocyclic compounds; ketones; reducing agents; ruthenium; stereochemistry

DESCRIPTION: (Principal Investigator's Abstract) The medicinal chemist relies on the tools of organic synthesis to prepare new therapeutic agents, or to prepare molecules to study the mechanism of action of existing therapeutic agents. Given the importance of chirality in the biological activity of drugs, medicinal chemists need methods for the preparation of enantiomerically and diastereomerically pure molecules. This grant supports a research program the aims of which are to discover new stereoselective and chemoselective reactions and reagents in organic synthesis. The tools of mechanistic organic chemistry are used to study the mechanism of action of selective reagents and catalysts. The results of these studies are then used to devise new reagents and catalysts that offer advantages over the original. In this proposal, a continuation of work on the development of enantioselective reducing agents for ketones and aldehydes using chiral ruthenium complexes is described. The use of these complexes in the kinetic resolution of chiral alpha- and beta-alkoxy aldehydes and ketones will be studied. A second chiral reducing agent is described that is based on work undertaken in the last funding period wherein hydroxyl-directed catalysts which bear separate binding and catalytic sites were designed and their mechanisms studied. This reducing agent is derived from the Corey-Bakshi-Shibata (CBS) catalyst which has been rendered alkoxy-directed by the incorporation of a binding site. As in the ruthenium derived system, the kinetic resolution of chiral alpha- and beta-alkoxy aldehydes and ketones will be studied with this catalyst. Also, the synthesis of skipped 1,3,5-triols will be undertaken, the application of this chemistry being to the synthesis of the antifungal agent mycoticin. A second project relates to the use of vinyl oxocarbenuim ions in the ionic Diels-Alder reaction. This ongoing project focuses on studying the stereoselectivity of this reaction, especially in systems which can display remote asymmetric induction. Finally, the synthesis of substituted heterocycles using variants of the halogen dance and the newly ,discovered tin dance reaction is described.

描述：（主要研究者摘要）药物化学家依赖于 有机合成的工具，以制备新的治疗药物，或 制备分子以研究现有治疗药物的作用机制 剂.鉴于手性在药物生物活性中的重要性， 药物化学家需要制备对映体和 非对映异构体纯的分子。这项拨款支持一项研究计划， 其目的是发现新的立体选择性和化学选择性反应， 和有机合成试剂。机械有机化学的工具 用于研究选择性试剂和催化剂的作用机理。 这些研究的结果被用来设计新的试剂和催化剂 比原版有优势在本提案中， 致力于开发酮的对映选择性还原剂， 描述了使用手性钌络合物的醛。使用这些 手性α-和β-烷氧基醛动力学拆分中的络合物 和酮将被研究。描述了第二手性还原剂，其 基于上一个供资期开展的工作， 带有单独结合和催化位点的羟基导向催化剂 并对其机制进行了研究。该还原剂来源于 已被赋予烷氧基导向Corey-Bakshi-柴田（CBS）催化剂 通过结合位点的结合。如在钌衍生体系中， 手性α-和β-烷氧基醛和酮动力学拆分将 用这种催化剂进行研究。此外，跳过的1，3，5-三醇的合成将 在这种情况下，这种化学的应用是合成的。 抗真菌剂真菌素。第二个项目涉及使用乙烯基 在离子Diels-Alder反应中的氧代卡宾离子。这个正在进行的项目 重点研究了该反应的立体选择性，特别是在 可以显示远程不对称感应的系统。最后，综合 取代的杂环，使用卤素舞的变体和新的 描述了发现的锡舞反应。