In FBDD, medicinal chemists often face synthetic tractability challenges which make synthesis rate-limiting for the fragment-to-lead (F2L) process. State-of-the-art chemical methodologies such as electrochemistry, photoredox catalysis and C–H activation provide new opportunities for enabling difficult growth vectors; however, they are largely untested on fragments and fragment-like molecules.
Recent developments in synthetic technologies, like robotics for high-throughput experimentation (HTE), provide new opportunities to enable chemistry in FBDD in a standardised, reproducible and robust way. This project aims to utilise these innovative technologies to expedite reaction development in FBDD; the speed and reliability of HTE and automated synthesis technologies will be exploited to assess the innate reactivity of fragments using novel activation modes such as electrochemistry, photoredox and C–H activation.
The information gained from this project will help with our continued goal to construct a chemical reactivity map around fragments and address intrinsic challenges in FBDD such as elaborating fragments which have poorly accessible growth vectors (so-called unsociable fragments).