TRANSITION METAL CATALYZED C-C BONDING FORMING REACTION

描述：(申请人摘要)合成有机化学继续 在优化生物治疗活性中发挥主导作用 主动结构。我所在团队的研究方向是开发 新型过渡金属催化碳-碳键形成反应 适用于不饱和底物的碳环化。我们的目标是 为有机合成提供新的环化方法，利用 常见的有机官能团，并在金属中进行催化。到目前为止我们的 方法一直是解决自行车运动的两个机械性方面，如 以及非常简单的新方法的合成应用。前一部 资助期标志着从方法论向综合化转变 申请。这一竞争性续订申请延续了这一趋势。论 在之前的基础上完成的发现和开发工作 NIH的支持对无障碍环路系统进行了很好的调查， 可容忍的功能和立体化学控制 铁催化的二烯碳环化和钯催化的双二烯 碳环化反应。我们现在将更有针对性的问题集中在合成 与药物相关的分子。这项提议的具体目的是 证明这些新的键结构作为战略层面的可行性 用于复杂分子全合成的反应。目标包括A80577， 前列腺素、布雷菲尔丁和类固醇。他们的合成是为了利用 有机金属中间体的独特结构和活性来控制 碳-碳键结构的立体化学和区域化学过程，但 并不是我们现在知道的简单的化学应用。每个应用程序都是 旨在推动金属环化方法的极限，以及 因此，需要有针对性的发展工作才能取得成功。

DESCRIPTION: (Applicant's Abstract) Synthetic organic chemistry continues to play a dominant role in optimizing the therapeutic-activity of biologically active structures. Research in my group is directed toward the development of novel catalytic transition-metal-mediated carbon-carbon bond forming reactions applied to the carbocyclization of unsaturated substrates. Our goal is to provide novel cyclization methodologies for organic synthesis that utilize common organic functional groups and proceed catalytic in metal. To date our approach has been to address both mechanistic aspects of the cyclizations as well as very simple synthetic applications of the new methods. The prior funding period marked a transition away from methodology and toward synthetic applications. This competitive renewal application continues that move. On the basis of the discovery and developmental work that was completed under prior NIH support there is a good survey of the accessible rings systems, functionalities tolerated and the stereochemical control in both the iron-catalyzed enediene carbocyclizations and the palladium-catalyzed bisdiene carbocyclizations. We now focus more targeted problems in the synthesis of pharmaceutically relevant molecules. The specific aim of the proposal is to demonstrate the viability of these novel bond constructions as strategy-level reactions for complex molecule total synthesis. The targets include A80577, prostanoids, brefeldin, and steroids. Their syntheses are designed to exploit the unique structure and reactivity of organometal intermediates to control the stereochemical and regiochemical course of carbon-carbon bond construction, but are not simply applications of chemistry we now know. Each application is designed to push the limits of the metal-mediated cyclization methodology, and as such will require targeted developmental work to be successful.