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.

项目摘要 该项目开发的基础技术是Photoredox催化，这是一个活跃的研究领域 发展学术和工业兴趣。预计光电毒素催化的影响将超过钯 催化作用，诺贝尔奖获奖的化学反应促进了毒品发现的黄金时代。光毒素催化 使用光激活化学反应，而不是在常规过程中加热。唯一的单电子 通过光吸收获得根本化学，实现新的反应率和前所未有的过程 效率，例如较少步骤的候选毒品合成。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和结构上多样的原材料，否则 在常规过程中无反应。从公共卫生的角度来看，Photoredox催化具有潜力 通过实现加速药物，可以大大降低治疗剂的成本并改善整体人类健康 开发和降低药物制造成本。 完成此NIH SBIR II期项目将导致高性能有机商业化 Photoredox催化剂（PC）产品。 PC是光电毒素催化的关键推动力。但是，PC 今天主要使用的是基于虹膜和唯一，两种稀有且昂贵的贵金属 不超过研发的规模，构成了工业用途的严重成本和供应问题。有机PC提供 解决方案。它们是由丰富的元素制成的，它们是可持续的，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，以具有关键特性 解决早期几代的许多局限性。在许多应用中，它们被证明是匹配的，在某些应用中 案例超过了贵金属PC的性能。这里开发的有机PC提供了可扩展的 用于药物开发和制造所需的光电毒催化解决方案。 具体而言，该项目集成了三个主要组成部分，以实现工业应用 光电毒素催化，即i）有机PC，ii）光化学反应和iii）光反应器技术。为了 有机PC（目标1和2），许多PC候选者将通过扩展的反应性范围合成 能够适应许多工业反应条件。对于光化学反应（目标3和4）， 新颖和具有医学重要的反应（具有扩展的基板范围）会陈述客户兴趣 使用各种类别的有机PC开发。最后，用于光电反应器的集成（AIM 5），商业上 将确定可用的光电反应器设计和相关的反应条件，使最大化 有机PC的性能。