Synthesis Based Upon Reactions of Oxocarbenium Ions

基于氧碳鎓离子反应的合成

• 批准号: 6833443
• 负责人: KEITH ALLEN WOERPEL
• 金额: $ 19.97万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6833443
• 关键词: alkaloids; biological products; carbene; chemical reaction; chemical synthesis; drug design /synthesis /production; imines; ionic bond; stereochemistry

DESCRIPTION: (provided by applicant) Oxocarbenium ions are important reactive intermediates in both bioorganic and synthetic organic chemistry. The goal of our research is to deepen our understanding of how steric and electronic effects govern the selective reactions of oxocarbenium and iminium ions and to use these effects to accomplish stereoselective transformations. During the proposed funding period, we will accomplish the following goals: (1) We will demonstrate that the powerful electronic effect exerted by heteroatom substituents on six-membered ring oxocarbenium and iminium ions will control the stereochemical outcomes of both intermolecular and intramolecular nucleophilic attack. (2) We will also show that a variety of heteroatom substituents can be used to control stereoselectivity in these reactions, and we will explore how several substituents interact to reinforce or oppose each other. These experiments will deepen our understanding of electronic influences on stereoselectivity as well as introduce new methods for forming various heteroatom-substituted oxygen and nitrogen heterocycles. (3) We will demonstrate that reactions of medium-ring oxocarbenium and iminium ions will also be controlled by the electronic nature of substituents, therefore leading to new approaches for remote asymmetric induction. (4) With a detailed knowledge of electronic effects on reactions of carbocations, we will demonstrate that this phenomenon can be used as a guiding principle for retrosynthetic analysis. We will complete syntheses of the alkaloid vincarodine, which has been shown to reverse multi-drug resistance in leukemia cells, and laurefucin, a marine natural product with a substitution pattern that will be a demonstration of the powerful influences of electronic effects on oxocarbenium ion conformation.

描述：(申请人提供)氧碳正离子在生物有机化学和合成有机化学中都是重要的活性中间体。的目标是 我们的研究是为了加深我们对空间和电子如何 影响控制氧碳正离子和亚胺离子的选择性反应，并 使用这些效果可以完成立体选择变换。在拟议的资助期内，我们将实现以下目标：(1) 我们将证明杂原子施加的强大电子效应 六元环上的取代基氧碳正离子和亚胺离子将起控制作用 分子间和分子内的立体化学结果 亲核攻击。(2)我们还将展示各种杂原子 取代基可以用来控制这些反应中的立体选择性，并且 我们将探索几个取代基如何相互作用来加强或反对每个取代基 其他的。这些实验将加深我们对电子影响的理解 关于立体选择性以及介绍形成不同种类的新方法 杂原子取代的氧和氮杂环。(3)我们会 证明了中环氧碳正离子与亚胺离子的反应将 也受取代基的电子性质控制，因此领先 到远程不对称诱导的新方法。(4)详细说明 关于碳正离子反应的电子效应的知识，我们将 证明这一现象可以作为指导原则 逆合成分析。我们将完成生物碱的合成 长春花碱，已被证明可以逆转白血病的多药耐药性 细胞，以及具有替代模式的海洋天然产物月桂茶素 这将是电子效应强大影响的一个例证。 氧碳正离子构象的研究。