Organic photoredox catalysts as sustainable and cost-effective replacement forprecious metal complexes in light-driven drug synthesis

有机光氧化还原催化剂作为光驱动药物合成中贵金属配合物的可持续且经济有效的替代品

• 批准号: 10011197
• 负责人: Chern-Hooi Lim
• 金额: $ 76.64万
• 依托单位: NEW IRIDIUM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-05 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011197
• 关键词: Age; Amines; Architecture; Area; Benchmarking; Catalysis; Chemistry; Coupling; Development; Electrons; Elements; Generations; Health; Human; Hydrophobicity; Industrialization; Iridium; Life; Light; Measures; Metals; Methods; Nobel Prize; Oxidants; Palladium; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Photochemistry; Process; Production; Property; Public Health; Reaction; Reducing Agents; Research; Route; Ruthenium; Safety; Savings; Scheme; Scientist; Small Business Innovation Research Grant; Solubility; Solvents; Structure; System; Technology; Therapeutic; Time; United States National Institutes of Health; absorption; aqueous; base; catalyst; chemical reaction; commercialization; cost; cost effective; design; drug candidate; drug development; drug discovery; drug synthesis; empowered; hydrophilicity; improved; interest; metal complex; novel; novel therapeutics; phenoxazine; quantum; research and development; simulation

PROJECT SUMMARY The underlying technology developed in this project is photoredox catalysis, an active research area with growing academic and industrial interest. The impact of photoredox catalysis is expected to exceed palladium catalysis, the Nobel-prize-winning chemistry that fueled the golden age of drug discovery. Photoredox catalysis uses light to activate chemical reactions, as opposed to heat in conventional processes. Unique single-electron radical chemistry is accessed through light absorption enabling new reactivities and unprecedented process efficiencies e.g. synthesis of drug candidates in fewer steps. Of additional industrial interest, it also permits the use of low-cost and structurally diverse raw materials in drug development and manufacturing that are otherwise unreactive in conventional processes. From a public health perspective, photoredox catalysis has the potential to substantially lower the cost of therapeutics and improve overall human health by enabling accelerated drug development and reduced drug manufacturing costs. Completing this NIH SBIR Phase II project will result in the commercialization of high performance organic photoredox catalyst (PC) products. PCs are the key enabler of photoredox catalysis. However, PCs predominantly used today are based on iridium and ruthenium, two rare and expensive precious metals that do not scale beyond R&D usage, posing serious cost and supply issues for industrial use. Organic PCs provide the solution. Made from abundant elements, they are sustainable and can easily scale to meet industrial demand. Notably, the organic PCs of interest here were designed by quantum simulations to possess critical properties resolving many limitations of earlier generations. In many applications, they were shown to match and in some cases exceed the performance of precious metal PCs. The organic PCs developed here provide the scalable solution for photoredox catalysis required for drug development and manufacturing. Specifically, this project integrates three main components pivotal to enabling industrial application of photoredox catalysis, namely i) organic PCs, ii) photochemical reactions, and iii) photoreactor technology. For organic PCs (Aims 1 and 2), a number of PC candidates will be synthesized with expanded ranges of reactivities capable of accommodating many industrial reaction conditions. For photochemical reactions (Aims 3 and 4), novel and medicinally important reactions (with extended substrate scope) with stated customer interest will be developed using various classes of organic PCs. Finally, for photoreactor integration (Aim 5), commercially available photoreactor designs and associated reaction conditions will be identified that maximize the performance of organic PCs.

项目概要 该项目开发的基础技术是光氧化还原催化，这是一个活跃的研究领域 日益增长的学术和工业兴趣。光氧化还原催化的影响力有望超过钯 催化作用，一种荣获诺贝尔奖的化学物质，推动了药物发现的黄金时代。光氧化还原催化 使用光来激活化学反应，而不是传统过程中的热。独特的单电子 通过光吸收获得自由基化学，从而实现新的反应性和前所未有的过程 效率，例如以更少的步骤合成候选药物。具有额外的工业利益，它还允许 在药物开发和制造中使用低成本且结构多样的原材料 在传统工艺中不发生反应。从公共卫生的角度来看，光氧化还原催化具有潜力 通过加速药物治疗，大幅降低治疗成本并改善人类整体健康 开发并降低药品生产成本。 完成这个 NIH SBIR 二期项目将导致高性能有机产品的商业化 光氧化还原催化剂（PC）产品。 PC 是光氧化还原催化的关键推动者。然而，个人电脑 如今主要使用的材料是铱和钌，这两种稀有且昂贵的贵金属 规模不能超出研发用途，给工业用途带来严重的成本和供应问题。有机 PC 提供 解决方案。它们由丰富的元素制成，具有可持续性，并且可以轻松扩展以满足工业需求。 值得注意的是，这里感兴趣的有机 PC 是通过量子模拟设计的，具有关键特性 解决了前几代产品的许多限制。在许多应用中，它们被证明是匹配的，并且在某些应用中 表壳的性能超越了贵金属 PC。这里开发的有机 PC 提供了可扩展的 药物开发和制造所需的光氧化还原催化解决方案。 具体来说，该项目集成了对于实现工业应用至关重要的三个主要组件 光氧化还原催化，即 i) 有机 PC，ii) 光化学反应，以及 iii) 光反应器技术。为了 有机 PC（目标 1 和 2），将合成许多具有扩大反应范围的候选 PC 能够适应许多工业反应条件。对于光化学反应（目标 3 和 4）， 新颖且具有医学重要性的反应（具有扩展的底物范围）以及明确的客户兴趣将是 使用各种类别的有机 PC 开发。最后，对于光反应器集成（目标 5），商业化 将确定可用的光反应器设计和相关的反应条件，以最大化 有机 PC 的性能。