New Catalytic Strategies for Metal-Free C-C Bond Formation

无金属 C-C 键形成的新催化策略

• 批准号: 2281174
• 金额: --
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2281174
• 关键词: New; Catalytic; Strategies; Metal; Free

Amines and N-heterocycles are key building blocks for pharmaceutical compounds, arising in 60% of all small-molecule drugs. However, a consortium of major pharmaceutical companies recently identified a lack of practical methods for N-heterocycle synthesis as a serious impediment to drug development (see Nature Chem. 2018, 10, 383). The problem is not that these structures cannot in principle be accessed, but that the existing technology to synthesise them is so laborious and time-consuming that chemists are often forced to overlook regions of chemical space that may well provide the most optimal drug candidates. The aim of this project is to find new synthetic methods for amine and N-heterocycle synthesis that can be easily applied in industry. My research will address the above challenges for some of the most highly sought-after N-heterocyclic scaffolds, including those containing only a single nitrogen atom and more exotic ring-systems comprising two nitrogen atoms.Our lab has recently discovered a ground-breaking process to functionalise carbon-hydrogen (C-H) bonds in simple, nitrogen-containing starting materials called primary amines, in which two different catalysts orchestrate a carbon-carbon (C-C) bond formation under visible-light irradiation. I will leverage this novel reactivity to design novel and innovative chemical transformations to assemble important N-heterocycles with unprecedented efficiency, requiring only a single synthetic operation. In contrast, the current state-of-the-art for these targets prescribes extended linear sequences of up to five (or more) chemical steps, so the contributions here are set to be transformative. We are further setting ourselves the challenge of ensuring that all of our processes are potentially executable on a process scale, which requires kilogram quantities of material. To achieve this goal, I will utilise modern flow chemistry techniques that run chemical reactions in tubing-based reactors, as opposed to conventional glassware. In conjunction with our industrial partner (AstraZeneca), I will also explore the potential for using automated robotic platforms in unity with our chemistry to generate novel libraries of high-value compounds for drug discovery.

胺和N-杂环是药物化合物的关键基础，在所有小分子药物中有60％产生。但是，主要制药公司的一个联盟最近确定缺乏N-杂环合成的实际方法是对药物开发的严重障碍（见Nature Chem。2018，10，10，383）。问题不是原则上无法访问这些结构，而是要合成它们的现有技术是如此艰辛和耗时，以至于化学家通常被迫忽略可能提供最佳候选药物的化学空间区域。该项目的目的是找到可以轻松应用于行业的胺和N-杂环合成的新合成方法。我的研究将针对某些最受欢迎的N型型脚手架的挑战，包括仅包含一个单个氮原子和包括两个氮原子的更异国情调的环形系统的脚手架的脚支架，它最近发现了一个突破性的过程，可以在碳质（C-H）中构成两种启动型ny nitrogen的突破性过程，从而启动了两种链接，从而启动了niTogents NITONT的纽带构造，该过程启动了nitrogen的启动，该过程启动了nItrogen，该过程启动了nItrogen，该过程构成了构造的构造，该过程构成了consent introgent introgent in nitor introgen。在可见光照射下编排碳碳（C-C）键形成。我将利用这种新颖的反应性来设计新颖和创新的化学转化，以前所未有的效率组装重要的N-杂环，仅需要一个合成操作。相比之下，这些目标的当前最新面积规定了最多五个（或更多）化学步骤的延长线性序列，因此这里的贡献将具有变换性。我们进一步为确保我们所有的过程都可以在过程量表上执行，这需要千克数量。为了实现这一目标，我将利用现代流动化学技术在基于管道的反应器中运行化学反应，而不是传统的玻璃器皿。与我们的工业合作伙伴（阿斯利康）一起，我还将探索使用与我们的化学统一的自动化机器人平台来生成高价值化合物的新型图书馆进行药物发现的潜力。