CAREER: SusChEM: New organocatalytic approaches to the stereo- and regioselective construction of acetals

职业：SusChEM：缩醛立体和区域选择性构建的新有机催化方法

• 批准号: 1350060
• 负责人: Pavel Nagorny
• 金额: $ 60.32万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 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: 2014-01-15 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1350060&HistoricalAwards=false
• 关键词: CAREER; SusChEM; New; organocatalytic; approaches

With this award, the Chemical Catalysis Program of the Division of Chemistry supports the research of Professor Pavel Nagorny of the Department of Chemistry at the University of Michigan. This research project develops new chiral catalyst-controlled stereoselective transformations that proceed through highly reactive oxocarbenium ion intermediates. The chemistry of oxocarbenium ions is central to the synthesis of acetal-containing compounds such as carbohydrates and spiroketals, as well as heterocyclic compounds containing tetrahydrofuran and tetrahydropyran moieties. These functionalities are also present in numerous bioactive natural products as well as drugs and are often vital to the biological properties of these compounds. Harnessing the reactivity of oxocarbenium ions is a long-standing challenge, which is addressed utilizing chiral phosphoric acid-based catalysts to control the course of important transformations proceeding through the intermediacy of oxocarbenium ions. This project is focused on investigating catalyst-controlled stereo- and regioselective acetalization reactions. New chiral catalysts are synthesized and examined for the stereoselective/regioselective formation of spiroketals, acetals and glycosides. Structural and computational studies are performed to elucidate the mechanism of activation and the origins of selectivity. Mechanistic studies contribute to fundamental insights into catalyst structure and function, and provide opportunities for hypothesis-driven catalyst design. Professor Nagorny's research efforts revolve around the development of new chiral phosphoric acid-based transformations involving oxocarbenium ions and application of these transformations to the synthesis of bioactive compounds and natural products. These studies will produce new techniques that will enable the discovery of new small-molecule-based therapeutic agents and improve the understanding of fundamentally important chemical and biochemical processes. In addition, these efforts will advance the field of chemical synthesis and produce new catalysts that will allow chemists to shorten synthetic sequences, saving time, money and natural resources. This research is considered sustainable as it uses phosphorus-based catalysts (organocatalysts) rather than expensive, costly and sometimes toxic transition metal-based catalysts. In addition to the technical applications of the research, this project encourages sophomore undergraduate students to consider the historical, economic, social, psychosocial, societal and legal issues associated with pharmaceuticals design and production. Students will also be carefully trained to edit Wikipedia entries in order to learn how to explain their science to a broad and diverse audience.

通过此奖项，化学系的化学催化计划支持密歇根大学化学系帕维尔·纳戈尔尼教授的研究。该研究项目开发了新的手性催化剂控制的立体选择性转换，这些转换通过高反应性氧化核离子中间体进行。氧化碳离子的化学对于合成含有乙酰化化合物（例如碳水化合物和螺旋体）以及含有四氢呋喃和四氢吡喃部分部分的杂环化合物而言至关重要。这些功能也存在于许多生物活性天然产物和药物中，通常对这些化合物的生物学特性至关重要。 利用氧化核离子的反应性是一项长期的挑战，它利用基于手性磷酸的催化剂来解决通过氧化碳离子中间人进行重要转化的过程。该项目的重点是研究催化剂控制的立体和区域选择性乙酰化反应。 合成并检查了新的手性催化剂，并检查了螺旋体，乙酰糖和糖苷的立体选择性/区域选择性形成。进行结构和计算研究以阐明激活机理和选择性的起源。 机械研究有助于对催化剂结构和功能的基本见解，并为假设驱动的催化剂设计提供了机会。 Nagorny教授的研究工作围绕着涉及氧化碳离子的新型手性磷酸转化的发展以及这些转化在生物活性化合物和天然产物的合成中的应用。这些研究将产生新的技术，以发现新的基于小分子的治疗剂，并提高对根本重要的化学和生化过程的理解。此外，这些努力将推进化学合成领域，并产生新的催化剂，使化学家能够缩短合成序列，节省时间，金钱和自然资源。 这项研究被认为是可持续的，因为它使用基于磷的催化剂（有机催化剂）而不是昂贵，有时有毒过渡金属的催化剂。 除了研究的技术应用外，该项目还鼓励大二本科生考虑与药品设计和生产相关的历史，经济，社会，社会，社会，社会和法律问题。 还将对学生进行仔细培训，以编辑Wikipedia条目，以了解如何向广泛而多样的受众解释他们的科学。