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：
10326379
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.

摘要：我们研究计划的中心目标是为后期开发新平台。近年来，这些努力已经实现了小分子和生物分子（例如蛋白质）的功能化。专注于光氧化还原催化作为合成化学中独特的范例的应用。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反应性开壳自由基物种，为反应创造了新的机会开发，在合成序列中提供高度可行的、新颖的键断开。其中光氧化还原催化的应用取得显着成功的是金属光氧化还原催化，光催化与过渡金属催化的结合促进了金属光氧化还原平台的发展。进入反应平台，使非传统合作伙伴能够参与交叉偶联化学。因此，我们的团队和其他人的努力解决了许多长期存在的综合挑战。研究提案概述了光氧化还原协议有潜力实现的新领域研究计划 I 的目标是开发新的光氧化还原介导的。能够选择性生物共轭天然酪氨酸和蛋氨酸残基的方法在研究计划 II 中，我们建议利用蛋白质在药物输送和生物成像中的应用。光氧化还原催化可逆地裂解和形成 C-H 键的能力将促进这一策略。氢同位素交换将能够动态控制 C-H 立体化学，应用于最后，研究计划 III 旨在探索上坡异构化和动态动力学解析。金属光氧化还原催化的新方向，例如利用光氧化还原激活模式规避铜和钴催化中具有挑战性的基本步骤，以及扩大实用性和镍/光氧化还原双重催化的范围。