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.

抽象的。我们的研究计划的一个核心目标是为晚期开发新平台小分子和生物分子等蛋白质的功能化。近年来，这些努力已经专注于将光毒素催化作用作为合成化学中的独特启示范式的应用。光催化剂的独特特征，特别是它们容易影响单电子转移的能力从而产生反应性开放式激进物种，为反应创造了新的机会开发，在合成序列中提供了高度启示的新型键断离。一个区域光电毒素催化的应用非常成功的是metallaphotoredox催化，光催化与过渡金属催化的结合。 metallaphotoredox平台有助于进入反应平台，使非传统伙伴能够参与交叉耦合化学。彼此之间，我们小组和其他人的努力已经解决了许多长期的综合挑战。这研究建议概述了Photoredox协议有可能实现的新领域重大影响。研究计划的目的是开发新的Photoredox介导的将使酪氨酸和方法残差的选择性生物结合的方法蛋白质用于药物输送和生物成像。在研究计划II中，我们建议利用光电毒素催化可逆清除并形成C – H键的能力。该策略将有助于氢同位素交换，并将启用C – H立体化学的动态控制以进行应用上坡异构化和动态动力学溶液。最后，研究计划III旨在探索金属局部毒性催化中的新方向，例如利用光电毒素激活模式规避铜和钴催化中的挑战基本步骤，以及扩大效用和镍/光电氧双催化的范围。