A common problem encountered by medicinal chemists is synthetic intractability. This issue can have a huge impact on the drug development process; challenging syntheses not only impact the time it takes to access target compounds, but in severe cases, it may cause us to abandon promising drug designs due to a lack of synthetic precedent.

This project focused on the use of robotic platforms to enable automated synthesis in FBDD. The ability to perform and analyse hundreds or thousands of reactions a day is transformative for a synthetic chemist. In FBDD, this gives us the opportunity to rapidly optimise reaction conditions, speeding up the time it takes us to progress an initial fragment hit to a prospective drug candidate. Furthermore, using an automated approach to synthesis we can broaden the chemical space that we work in, allowing us to explore the use of state-of-the-art synthetic methods such as transition metal catalysed C–H activation and photoredox catalysis to achieve precision synthesis of challenging bonds in fragment drug growth and elaboration.

Dr Rachel Grainger is now a Research Associate in the Chemistry Department, Astex Pharmaceuticals, UK.