Monday 15 April 2024

Student Research: Insights into Powerful Reactions for Drug Discovery

Recent DPhil graduate Dr Violeta Stojalnikova (DPhil Organic Chemistry, 2018), researcher at the Department of Chemistry, was lead author in a study on how ‘Chelation enables selective enantioconvergent Suzuki–Miyaura coupling’, a process that has provided critical insights for drug discovery. The paper has been published in the prestigious journal, Nature Chemistry.


Dr Violeta Stojalnikova and her collaborators, Stephen Webster and Ke Liu, and Professor Stephen Fletcher, discovered a way to ‘asymmetrically add aromatic and heteroaromatic rings to racemic mixtures of non-cyclic, non-symmetric allyl systems’.

The named ‘Suzuki–Miyaura-cross-coupling reaction’ uses chelation to convert both enantiomers of non-symmetrical starting materials into a single enantiomer of product.

Researchers realised a need to ‘reliably produce small molecules with a wider variety of structures’, allowing for novel ways to make chiral molecules enantioselectively – a critical advancement for new drug discovery.

Violeta and her collaborators are the first to achieve non-symettric allyl systems, with symmetric reactions being developed previously by The Fletcher Group to ‘synthesise biologically active and pharmacologically relevant molecules such as (S)-curcumene and the antidepressant sertraline (Zoloft®)’.

Asymmetric addition to a racemic starting material bearing an CO2Et group is used to generate a variety of functionalized products, and alkyl, branched and aromatic rings are tolerated at the centre where the stereogenic centre is controlled.

Regarding the possibilities of this advancement, Dr Violeta Stojalnikova says:

There are vast possibilities that this new reaction unlocks, and we are excited to see all the creative ways medicinal chemists are going to use it.