Synthesis of Quaternary Stereocentres via Hydrogen Borrowing Catalysis

University of Oxford

Improving methods of making 3D molecules to create better medicines
The function of a drug molecule is determined by its shape and structure, and by the atoms that make up its 3D structure. Lead molecules, which are to be developed into new medicines, often have a largely flat, almost 2D-like, molecular shape which tends to result in binding to a range of target proteins. This lack of selectivity results, in part, from a mismatch with the 3D shape of the binding ‘pocket’ of the target protein. Candidate drugs with a more specific 3D shape and therefore highly optimised molecular recognition for these 3D binding pockets will generally result in more targeted biological activity, with reduced potential for side effects.

Making such 3D drugs has proved difficult in the past and often requires highly dense packing of functional groups (relevant groups of atoms with distinct properties) around a single carbon atom. Jessica’s research will investigate how a new method of forming carbon-carbon bonds, the bonds that form the skeleton of many drugs, called ‘hydrogen-borrowing catalysis’, can be employed to bring multiple functional groups around single carbon atoms, fully exploring the available 3D space. The ‘hydrogen-borrowing’ method has distinct advantages over existing methods because the chemicals required for its function can be derived from sustainable chemical feedstocks, and it produces zero toxic waste.

This research seeks to bolster the pharmaceutical industry with insights into how to produce the next generation of highly potent and selective drugs for specific biological targets. It also has the potential to reduce the costs and environmental impact involved in developing complex drug candidates, providing economic and therapeutic benefit to patients globally.

Jessica completed her Master’s degree in Chemistry at the University of Oxford, Somerville College in 2020, and is currently a PhD student in the Synthesis for Biology and Medicine CDT at the University of Oxford. She has won a number of scholarships and prizes during her studies including the Gibbs Prize, Principal’s Prize, Bryant Scholarship and Haynes Scholarship. During her time at Oxford, Jessica has worked as a personal tutor and continued to pursue her passion in outreach and public engagement, developing an outreach programme about the science behind cooking and baking. Jessica also acts as Event Coordinator on the committee for the Oxford Women in Chemistry society.


“The complex 3D structures of many drug targets are often not well matched to the repertoire of available drug-like molecules. This new chemical method will enable easier access to more selective, 3D, drug-like molecules, and has the potential to pave the way for more efficient and sustainable production methods for future medicines.”