Synthesis Based Upon Reactions of Oxocarbenium Ions

描述：（由申请人提供）氧碳正离子具有重要的反应活性 生物有机化学和合成有机化学的中间体。的目标 我们的研究是为了加深我们对空间和电子 效应支配氧碳正离子和亚胺正离子的选择性反应， 使用这些效应来完成立体选择性转化。 在建议的拨款期内，我们会达致以下目的：（1） 我们将证明杂原子所产生的强大的电子效应 六元环氧代碳鎓和亚胺鎓离子上的取代基将控制 分子间和分子内的立体化学结果 亲核攻击(2)我们还将证明， 取代基可用于控制这些反应中的立体选择性， 我们将探讨几个取代基如何相互作用，以加强或反对每个 其他.这些实验将加深我们对电子影响的理解 立体选择性以及介绍新的方法，形成各种 杂原子取代氧和氮杂环。(3)我们将 证明中环氧碳正离子和亚胺离子的反应将 也由取代基的电子性质控制，因此导致 远程非对称感应的新方法。(4)的详细 碳阳离子反应的电子效应的知识，我们将 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 已被证明可逆转白血病的多药耐药性的长春定 细胞和月桂酸，一种具有替代模式的海洋天然产物 这将是电子效应的强大影响力的展示 对氧碳正离子构象的影响

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.