CAREER: Reactive Intermediate Promoted Polycyclization Reactions

在化学学部有机动力学项目的支持下，加州大学戴维斯分校的Dean J. Tantillo教授将进行多环化机制的理论和实验研究，该多环化机制是由有机反应中间体的生成引发的，被称为反应性中间体促进多环化（RIPP）反应。多环化反应，即分子形成多个新环的单一转化，是已知最有效的化学转化之一。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尚不清楚。提出的现代量子化学将用于阐明在各种化学环境下合成和生物合成的RIPP反应的机制。课程将特别强调使用“theozyme”（理论酶）方法获得对催化多环化过程的定量理解，以及以前未在自然界中观察到的新反应的理论设计，也未在实验室中尝试过，这种策略被Tantillo教授称为“从头开始反应设计”。本研究的总体目标是为设计高效的多环化工艺提供一套详细的指导方针。有机和大分子化学项目支持加州大学戴维斯分校的Dean J. Tantillo教授，他在本提案中描述的项目旨在使学生能够构建完整的故事，包括理论模型的发展，以解释实验观察，将这些模型应用于新反应的设计，并通过实验室实验对这些设计进行测试。这些研究的结果将在资助期间由PI和他的学生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.