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

通过这个奖项，化学系的化学催化项目支持了密歇根大学化学系Pavel Nagorny教授的研究。本研究项目开发了一种新的手性催化剂控制的立体选择转化，该转化通过高活性的氧羰基离子中间体进行。氧羰基离子的化学性质是合成含缩醛化合物的核心，如碳水化合物和螺旋酮，以及含有四氢呋喃和四氢吡喃基团的杂环化合物。这些功能也存在于许多生物活性天然产物以及药物中，并且通常对这些化合物的生物学特性至关重要。利用氧羰基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羰基离子中间体进行的重要转化过程。本项目主要研究催化剂控制的立体和区域选择性缩化反应。合成了新的手性催化剂，并对其立体选择性/区域选择性生成螺旋酮、缩醛和糖苷进行了研究。进行了结构和计算研究，以阐明活化机制和选择性的起源。机理研究有助于深入了解催化剂的结构和功能，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着开发新的手性磷酸基转化，包括氧羰基离子，并将这些转化应用于生物活性化合物和天然产物的合成。这些研究将产生新的技术，从而能够发现新的小分子治疗药物，并提高对重要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，因为它使用的是磷基催化剂（有机催化剂），而不是昂贵、昂贵、有时有毒的过渡金属基催化剂。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物设计和生产相关的历史、经济、社会、心理社会、社会和法律问题。学生们还将被认真训练编辑维基百科条目，以学习如何向广泛和多样化的受众解释他们的科学。

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.