Abstract

The discovery of bioactive small molecules is a challenge that is central to both drug discovery and chemical biology. However, given that there may be >10^30 drug-like small molecules, how can we discover molecules with specific biological functions? The challenge is compounded by chemists’ highly uneven and unsystematic historic exploration of chemical space: the reliance of a small toolkit of reactions means that the known chemistry ‘universe’ is dominated by a small number of structural classes that are found in many different molecules.

First, I will explain how we can draw inspiration directly from the structures of nature’s bioactive small molecules: natural products. Second, I will explain how we have been inspired by how biosynthetic pathways emerge in the first place to develop our function-directed discovery approach: activity-directed synthesis. Finally, I will discuss the prospects for realising fully autonomous molecular discovery: this would require chemical design to be algorithmically-driven and all experimental tasks are fully automated and integrated.