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.

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