CAREER: Strategic Advancement of Chemical Theory and Computations towards Complex Synthetic Transformations

职业：化学理论和计算在复杂合成转化方面的战略进步

• 批准号: 1352663
• 负责人: Ha-Yeon Cheong
• 金额: $ 54.71万
• 依托单位: Oregon State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1352663&HistoricalAwards=false
• 关键词: CAREER; Strategic; Advancement; Chemical; Theory

In this CAREER award funded by the Chemical Catalysis program of the Chemistry Division, Professor (Paul) Ha-Yeon Cheong of Oregon State University is developing new software methods for applying computational chemistry to study reactions that form complex compounds useful for pharmaceutical technology and the study of biochemical processes. Many catalytic reactions are important for the synthesis of molecules that display useful pharmacological or biological properties; however, it is often a challenge to devise experimental methods to define the fundamental details of how these reactions proceed. Very often, computational methods can be used to provide such deeper insights. In this research project, new software and computational methods are being developed to improve the level of detail at which a catalytic reaction can be studied. The longer range impacts of such work would be to allow the chemist to use a computer to design a catalytic reaction to make a specific product, thus saving the time and expense of performing preliminary laboratory work. Professor Cheong's research project is expanding the reach of computations and theory towards the efficient elucidation of mechanisms and factors that control the reactivity and selectivity of chemical transformations involving structures with significant conformational flexibility and where the interactions responsible for the reactivity and selectivity are largely non-covalent, weak, and/or complex. Specifically, Professor Cheong is developing theoretical tools and applying these methods in order to determine the central factors that determine the mechanism and the stereoselectivity of: (i) site-selective desymmetrization of cis-1,2-diols by scaffolding organic catalysts; (ii) kinetic resolution of beta-amino alcohols by beta-hairpin peptide-catalyzed acylation, and (iii) phosphine-catalyzed nucleophilic coupling of allenoates. Ultimately, this line of research will inform experimentalists with an intuitive understanding of the key factors in order to design better reactions and processes. The developed software platform and the scientific discoveries are being shared with the public and experts alike via an online gallery. An introductory undergraduate course in academic and career development for students planning for a career in science and technology is being offered at the university. Finally, a student organization has been created where the goal is to provide peer mentorship and support structures between student peers across the post-secondary education strata.

在这个由化学系化学催化项目资助的CAREER奖中，俄勒冈州州立大学的（Paul）Ha-Yeon Cheong教授正在开发新的软件方法，用于应用计算化学研究形成复杂化合物的反应，这些反应对制药技术和生物化学过程的研究有用。 许多催化反应对于合成显示有用的药理学或生物学性质的分子是重要的;然而，设计实验方法来定义这些反应如何进行的基本细节通常是一个挑战。 通常，计算方法可以用来提供这种更深入的见解。 在该研究项目中，正在开发新的软件和计算方法，以提高研究催化反应的细节水平。 这项工作的长远影响是使化学家能够使用计算机设计催化反应以制造特定产品，从而节省进行初步实验室工作的时间和费用。Cheong教授的研究项目正在扩大计算和理论的范围，以有效阐明控制化学转化反应性和选择性的机制和因素，这些化学转化涉及具有显著构象灵活性的结构，并且负责反应性和选择性的相互作用主要是非共价的，弱的和/或复杂的。 具体来说，Cheong教授正在开发理论工具并应用这些方法，以确定决定以下机制和立体选择性的核心因素：（i）通过骨架有机催化剂对顺式-1，2-二醇进行位点选择性去对称化;（ii）通过β-发夹肽催化酰化反应对β-氨基醇进行动力学拆分;以及（iii）膦催化的联烯酸酯亲核偶联。 最终，这一系列的研究将为实验者提供对关键因素的直观理解，以设计更好的反应和过程。开发的软件平台和科学发现正在通过在线画廊与公众和专家分享。该大学正在为计划从事科学和技术职业的学生提供学术和职业发展方面的本科生入门课程。最后，成立了一个学生组织，其目标是在中学后教育阶层的学生之间提供同伴指导和支持结构。