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Figure: A new, versatile reaction enables heterobenzylic C-H fluorination.

A new tool for making drugs

The motivation Adding a fluorine atom to a drug molecule can have dramatic effects on its activity and improve its pharmaceutical properties. Not surprisingly, roughly 30% of all FDA approved pharmaceuticals contain at least one fluorine atom. Considering the importance of fluorine to drug discovery, there is great interest in finding new ways of adding fluorine atoms to molecules. This is especially critical, as drug molecules are often complex structures that mimic bio-molecules, and many of these biochemicals contain carbon rings that include nitrogen atoms (heterocycles). The goal of this study was to develop a convenient and effective reaction that allows for direct fluorination of heterocycles.   

The discovery – Researchers from the labs of Simon Fraser University’s Rob Britton and Paul Schaffer (TRIUMF), along with Dr. Rainer Martin from Hoffmann-La Roche Ltd. (Switzerland) discovered a unique reaction that allows for facile fluorination of heterocycle-containing molecules.  This reaction involves simply heating the heterocycle with a stable and commonly used fluorination reagent known as NFSI. While such reactions were expected to decompose the reagent NFSI, these researchers found that the decomposition product made the heterocycle highly susceptible to fluorination.

Its significance – Because heterocycles are a very common component of drug molecules and their presence often prevents fluorination, this significant new reaction provides an easy, straightforward way for medicinal chemists to tune the pharmaceutical properties of molecules. Furthermore, it may enable new approaches to developing radiotracers for positron emission tomography (PET) imaging.

This paper was selected by the Editor for the “2018 Chemical Science HOT Article Collection.”

Read the paper“Direct heterobenzylic fluorination, difluorination and trifluoromethylthiolation with dibenzenesulfonamide derivatives” by Michael Meanwell, Bharani Shashank Adluri, Zheliang Yuan, Josiah Newton, Philippe Prevost, Matthew B. Nodwell, Chadron M. Friesen, Paul Schaffer, Rainer E. Martin and Robert Britton. Chemical Science 2018(9):5608-5613 (2018) DOI: 10.1039/C8SC01221K

Website article compiled by Jacqueline Watson with Theresa Kitos