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Photoredox Catalysis Applications in Organometallics and Chemical Biology

光氧化还原催化在有机金属学和化学生物学中的应用

基本信息

批准号：
10544541
负责人：
David W MacMillan
金额：
$ 91.89万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2024-12-31
项目状态：
已结题

项目摘要

Abstract. A central goal of our research program is to develop new platforms for the late-stage functionalization of small molecules and biomolecules such as proteins. In recent years, these efforts have focused on the application of photoredox catalysis as a uniquely enabling paradigm in synthetic chemistry. The distinct features of photocatalysts, in particular their ability to readily effect single-electron transfers and thereby generate reactive open-shell radical species, have created new opportunities for reaction development, providing highly enabling, novel bond disconnections in synthetic sequences. An area in which the application of photoredox catalysis has been notably successful is metallaphotoredox catalysis, the combination of photocatalysis with transition-metal catalysis. Metallaphotoredox platforms facilitate entry into reaction platforms that enable non-traditional partners to participate in cross-coupling chemistry. Accordingly, efforts by our group and others have addressed many long-standing synthetic challenges. This research proposal outlines new fields in which photoredox protocols have the potential to achieve significant impact. The objective of Research Program I is to develop new photoredox-mediated methodologies that will enable the selective bioconjugation of tyrosine and methionine residues in native proteins for application in drug delivery and bioimaging. In Research Program II, we propose to harness the ability of photoredox catalysis to reversibly cleave and form C–H bonds. This strategy will facilitate hydrogen isotope exchange and will enable dynamic control of C–H stereochemistry for application in uphill isomerizations and dynamic kinetic resolutions. Finally, Research Program III aims to explore novel directions in metallaphotoredox catalysis, such as harnessing photoredox activation modes to circumvent challenging elementary steps in copper and cobalt catalysis, as well as to expand the utility and scope of nickel/photoredox dual catalysis.

抽象。我们研究计划的一个中心目标是为后期开发新的平台，小分子和生物分子如蛋白质的功能化。近年来，这些努力集中在光氧化还原催化的应用作为一个独特的合成化学使范例。光催化剂的独特特征，特别是它们容易实现单电子转移的能力从而产生活性开壳自由基物质，为反应创造了新的机会开发，提供高度使能的，新的键断开的合成序列。的区域其中光氧化还原催化的应用已经非常成功的是金属光氧化还原催化，催化剂与过渡金属催化剂的结合。金属光氧化还原平台促进进入反应平台，使非传统的合作伙伴参与交叉偶联化学。因此，我们集团和其他方面的努力解决了许多长期存在的综合挑战。这一项研究提案概述了光氧化还原协议有可能实现的新领域重大影响。研究计划I的目标是开发新的光氧化还原介导的这些方法将使得能够在天然细胞中选择性地生物缀合酪氨酸和甲硫氨酸残基，用于药物递送和生物成像的蛋白质。在研究计划II中，我们建议利用光氧化还原催化可逆裂解和形成C-H键的能力。这一战略将有助于氢同位素交换，并将使得能够动态控制C-H立体化学，用于上坡异构化和动态动力学拆分。最后，研究计划三旨在探索金属光氧化还原催化的新方向，如利用光氧化还原活化模式，规避铜和钴催化中具有挑战性的基本步骤，以及扩大实用性，镍/光氧化还原双重催化的范围。