Realising Fragment-Oriented Synthesis

Fragment-based approaches are a new paradigm in drug discovery, and rely on the biophysical screening of small (<19 heavy atom) molecules, known as fragments, at high concentrations to efficiently scope chemical space. The bottleneck in converting fragment 'hits' to tractable 'leads' for development into drug candidates is the requirement for de novo synthesis of larger derivatives of the initial hits. This project will form part of a larger EPSRC/industrially-funded project to find catalytic methods to directly functionalise fragment hits and thus accelerate the key fragment-to-hit stage, unblocking the bottleneck. Specifically, this project will focus on chemocatalytic methods for the functionalization of amines in the alpha, beta and gamma positions. The new methodologies will be road-tested on known (novel, proprietary to Leeds) protein-binding fragments.