Automated Late-Stage C-H Diversification of Complex Drugs and Natural Products

药物通常是高度复杂的分子，需要在其设计和开发中花费大量资源。药物的后期C-H官能化（LSF）允许调节高度官能化分子的性质，而无需进行从头设计和合成，从而允许成本和时间有效地生产用于不同目的的高效类似物。目前，该领域的一个主要限制是服从C-H键的LSF的化学反应很少，并且在大多数情况下仅允许引入一个特定的官能团。我们建议在这个项目中使用高通量反应筛选技术，发明一种新的反应，允许引入一个合成处理到芳香族化合物。反应条件必须以这样的方式发展，即大多数药物可以官能化，然后使用现代技术如光氧化还原或电化学催化进行多样化。最终，我们希望实现一个自动化的工作流程，其中机器人将使用将要开发的反应来多样化并制造先导化合物或商业药物的类似物。该项目由杨森制药（约翰逊&约翰逊）共同资助，并有可能在Beerse（比利时，杨森的主要研究中心）进行工业实习，作为博士课程的一部分。

Drugs are often highly complex molecules that require lots of resources spent in their design and development. The late-stage C-H functionalization (LSF) of drugs allows the modulation of the properties of highly functionalized molecules, without committing to de novo design and synthesis, allowing cost- and time-efficient production of highly potent analogues for different purposes. Currently, one major limitation in the field is that chemical reactions amenable to the LSF of C-H bonds are scarce, and in most cases allow the introduction of only one specific functional group. We propose in this project to use high-throughput reaction screening techniques to invent a new reaction that allows the introduction of a synthetic handle onto aromatic compounds. The reaction conditions must be developed in such way that most drugs can be functionalized and then diversified using modern technologies such as photoredox or electrochemical catalysis. Ultimately, we wish to implement an automated workflow in which a robot will use the reactions that will be developed to diversify and make analogues of lead compounds or commercial drugs. The project is co-funded by Janssen Pharmaceutica (Johnson&Johnson) and there is the possibility to undertake an industrial placement in Beerse (Belgium, main research site of Janssen) as part of the PhD programme.