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

点击翻译按钮获取中文摘要

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.