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.

凭借该奖项，化学部化学催化项目支持了密歇根大学化学系Pavel Nagorny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化，通过高反应性的氧碳鎓离子中间体进行。氧碳鎓离子的化学性质对于含缩醛化合物（例如碳水化合物和螺缩酮）以及含有四氢呋喃和四氢吡喃部分的杂环化合物的合成至关重要。这些功能也存在于许多生物活性天然产物和药物中，并且通常对这些化合物的生物特性至关重要。 利用氧碳鎓离子的反应性是一个长期存在的挑战，利用手性磷酸基催化剂来控制通过氧碳鎓离子中介进行的重要转化过程来解决这一挑战。该项目的重点是研究催化剂控制的立体和区域选择性缩醛化反应。 合成并检查了新的手性催化剂，用于螺酮缩醛、缩醛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制和选择性的起源。 机理研究有助于对催化剂结构和功能的基本了解，并为假设驱动的催化剂设计提供机会。 Nagorny 教授的研究工作围绕开发涉及氧碳鎓离子的新型手性磷酸基转化，以及将这些转化应用于生物活性化合物和天然产物的合成。这些研究将产生新技术，使新的小分子治疗药物的发现成为可能，并提高对根本上重要的化学和生化过程的理解。此外，这些努力将推动化学合成领域的发展，并生产新的催化剂，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，因为它使用磷基催化剂（有机催化剂），而不是昂贵、昂贵且有时有毒的过渡金属基催化剂。 除了研究的技术应用之外，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、心理、社会和法律问题。 学生还将接受编辑维基百科条目的精心培训，以便学习如何向广泛而多样化的受众解释他们的科学。

项目成果

Exploration of chiral diastereomeric spiroketal (SPIROL)-based phosphinite ligands in asymmetric hydrogenation of heterocycles

基于手性非对映螺缩酮（SPIROL）的次亚膦酸酯配体在杂环不对称氢化中的探索

• DOI: 10.1039/d0cc03088k
• 发表时间: 2020-07
• 期刊: Chemical Communications
• 影响因子: 4.9
• 作者: Sun, Siyuan;Nagorny, Pavel
• 通讯作者: Nagorny, Pavel