CAREER: Design and Synthetic Applications of New Multicomponent Reactions

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。美国国家科学基金会化学部的有机和大分子化学项目支持加州大学戴维斯分校的Jared T. Shaw教授。他将开发一种新的反应性范例，使多组分反应（mcr）的设计和发现成为可能。mcr是由简单的起始物质在一次操作中形成复杂产物的反应，它只能从反应性的仔细平衡中产生，从而使连续的成键事件按顺序进行。在这些反应中，最有价值的是那些每个成分都可以独立于其他成分而变化的反应。肖教授发现了一种新的四组分反应（4CR），它以高产量生成具有两个或三个立体中心的高非对映选择性的γ -内酰胺。重要的是，这种“绿色”反应发生在一种无害的溶剂中，并产生水作为唯一的反应副产物。这个新的4CR构成了提案中描述的该领域更大的研究项目的基础。所提出的研究将证明所观察到的反应模式对发现新反应具有预测价值。该研究方向的主要成果包括：(1)以前所未有的效率组装具有多个立体中心的杂环化合物的新反应；(2)合成以mcr为中心组装核心结构的复杂天然产物的新方法。mcr和天然产物目标的合成将形成概念节点，可以连接不同的科学领域和不同的社会部门。由于mcr提供了快速合成具有有趣的生物或物理特性的分子的机会，PI将从其他部门征求可以使用这种策略执行的合作项目。这种方法将允许本科生学习如何制造有机分子，更重要的是，为什么他们的努力对其他学科很重要。肖教授将与一个高中班级合作，在加州大学戴维斯分校的植物园设计和安装一个展览，突出展示加州本土药用植物的化学成分。植物园将提供一个理想的环境，让市民了解药物所用化合物的来源，并激发他们进一步研究合成天然化合物的热情。提案中描述的研究和教育计划将把mcr和化学合成结合起来，以推进科学前沿，教育下一代科学家，并与公众联系。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).The Organic and Macromolecular Chemistry Program in the Chemistry Division at the National Science Foundation supports Professor Jared T. Shaw at the University of California at Davis. He will develop a new paradigm of reactivity that will enable the design and discovery of multicomponent reactions (MCRs). MCRs are reactions that form complex products from simple starting materials in a single operation, which can only emerge from a careful balance of reactivity that allows the successive bond-forming events to proceed in sequence. Among these reactions, the most valuable are those in which each of the components can be varied independently of the others. Professor Shaw has discovered a new four component reaction (4CR) that forms gamma-lactams in high yield with two or three stereogenic centers in high diastereoselectivity. Importantly, this "green" reaction takes place in a benign solvent and produces water as the only reaction by-product. This new 4CR forms the basis for a larger research program in this area that is described in the proposal. The studies that are proposed will demonstrate that the reactivity pattern observed has predictive value in the discovery of new reactions. The following outcomes of the proposed line of research are (1) new reactions of unprecedented efficiency for the assembly of heterocyclic compounds with multiple stereogenic centers, and (2) new approaches to the synthesis of complex natural products centered on MCRs for the assembly of core structures.MCRs and the synthesis of natural products targets will form conceptual nodes that can connect different areas of science as well as different sectors of society. Because MCRs offer the opportunity for rapid synthesis of molecules with interesting biological or physical properties, the PI will solicit collaborative projects from other departments that can be executed using this strategy. This approach will allow undergraduate students to learn how to make organic molecules and, more importantly, why their efforts are important to other disciplines. Professor Shaw will work with a high school class on the design and installation of an exhibit at the UC Davis arboretum that highlights the chemical components of medicinal plants native to California. The arboretum will provide an ideal setting for educating the public on the origin of chemical compounds used in medicines and inspire enthusiasm in further study of natural compounds through synthesis. The research and education plans described in the proposal will unite MCRs and chemical synthesis for the purpose of advancing the frontiers of science, educating the next generation of scientists, and connecting with the general public.