CAREER: Reactive Intermediate Promoted Polycyclization Reactions

在化学系有机动力学项目的支持下，加州-戴维斯大学的Dean J. Tantillo教授将进行研究，包括对由有机反应中间体产生引发的多环化机制的理论和实验研究，称为反应中间体促进的多环化（RIPP）反应。多环化反应，其中形成具有多个新环的分子的单一转变，是已知的最有效的化学转变之一。 然而，在许多情况下，几何、立体电子、静电和疏水效应在控制多环化的速率、区域选择性和立体选择性方面的相对重要性是未知的。建议现代量子化学将用于阐明在各种化学环境中的合成和生物合成RIPP反应的机制。特别强调的是将被放置在使用“theozyme”（理论酶）方法获得多环化过程的催化的定量理解和新的反应的理论设计上没有以前观察到的性质，也没有以前尝试在实验室中，一个策略，教授坦蒂洛呼吁“从头反应设计”。拟议的研究的总体目标是提供一套详细的指导方针，设计有效的多环化过程。 有机和大分子化学计划支持教授院长J.坦蒂洛的加州-戴维斯的大学，其项目中描述的本建议书的目的是让学生可以构建完整的故事，涉及理论模型的发展，解释实验观察，这些模型的应用，以设计新的反应，并通过实验室实验测试这些设计。这些研究的结果将在PI及其学生在资助期间组织的年度会议上发表，该会议将汇集来自研究生和本科教育机构以及制药和软件开发行业的理论和计算化学家。

With the support of the Organic Dynamics Program in the Chemistry Division, Professor Dean J. Tantillo of the University of California- Davis will perform research that consists of both theoretical and experimental studies of polycyclization mechanisms that are initiated by the generation of an organic reactive intermediate, referred to as Reactive Intermediate Promoted Polycyclization (RIPP) reactions. Polycyclization reactions, single transformations in which molecules with multiple new rings are formed, are among the most efficient chemical transformations known. In many cases, however, the relative importance of geometric, stereoelectronic, electrostatic and hydrophobic effects in controlling the rate, regioselectivity and stereoselectivity of polycyclization is not known. The proposed Modern Quantum Chemistry will be used to elucidate the mechanisms of both synthetic and biosynthetic RIPP reactions in various chemical environments. Particular emphasis will be placed on obtaining a quantitative understanding of catalysis of polycyclization processes using the "theozyme" (theoretical enzyme) method and on the theoretical design of new reactions not previously observed in nature and not previously attempted in the lab, a strategy that Professor Tantillo calls "ab initio reaction design". The overall goal of the proposed research is to provide a detailed set of guidelines for designing efficient polycyclization processes. The Organic and Macromolecular Chemistry Program supports Professor Dean J. Tantillo of the University of California- Davis whose projects described in this proposal are designed so that students can construct complete stories that involve the development of theoretical models to explain experimental observations, application of these models to the design of new reactions, and testing of these designs through laboratory experiments. The results of these studies will be presented at an annual conference that will be organized during the grant period by the PI and his students, which will bring together theoretical and computational chemists from graduate and undergraduate educational institutions and from the pharmaceutical and software development industries.