This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: When drugmakers want to improve on compounds they have already created, they can replace a carbon atom with a nitrogen atom. While effective, the techniques they use to perform this chemical swap, known as skeletal editing, have some downsides.
For example, older approaches often require harsh chemicals or only work on specific types of molecules. That got researchers led by Mark D. Levin at the University of Chicago searching for a gentler and more versatile way to do it.
Unlike older methods that fail when a specific chemical step goes wrong, their new technique turns that exact problem into a helpful tool. The new process involves three main steps, as the team details in their paper published in the journal Science. First, they started with ring-shaped molecules containing an added group of nitrogen atoms.
Next, they shone a blue light on them in the presence of oxygen and a reagent called tetramethylthiourea, setting off a series of reactions that opened up the carbon ring and rearranged its atoms. Finally, a further chemical treatment sealed the ring back together, leaving the new nitrogen atom in place of the old carbon atom. Earlier approaches ran into a problem at this stage.
Right after the light hit the molecule, the process would stall because a reactive chemical switched into a state in which it could no longer rearrange. Instead of trying to prevent that state, the researchers added the reagent, which allowed the molecule to complete the swap through a different reaction. "By embracing rather than avoiding this otherwise parasitic spin state, we achieve a reaction with much more versatile applicability, enabling the interrogation of C-to-N replacement in genuinely complex natural products," commented the study authors.
To demonstrate their new technique actually worked, the team tried it out on several families of ring-shaped molecules commonly found in pharmaceuticals. They successfully performed the carbon-to-nitrogen swap across dozens of different compounds. These included the heart-rhythm drug dronedarone as well as the pharmacologically active compounds vinpocetine, yohimbine and catharanthine.
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