University of MichiganJul 2 2024 The class of compounds, called azetidines, had been previously identified as a good candidate to build therapeutic drugs, but the compounds are difficult to produce in chemical reactions. Now, a team led by University of Michigan chemist Corinna Schindler has developed a method to produce a specific class of azetidines called monocyclic azetidines using visible light and a photocatalyst. Their results are published in the journal Science.
Instead, researchers suggest using monocyclic azetidines, a more stable four-membered ring system. But, says Emily Wearing, lead author of the study who recently earned her doctorate from Schindler’s lab, the key reactions chemists use to produce azetidines have specific challenges. In the reaction, the researchers used two classes of compounds called acyclic imines and alkenes, which are highly desirable as starting materials because they can be easily varied to produce different products, Wearing says. However, when you use light to excite the imine, the acyclic imine decays from the excited state before it can undergo the cycloaddition, Schindler says.
Their method uses visible light and a photocatalyst to allow access to the required excited state intermediates in what’s called an aza Paternò-Büchi reaction. To determine exactly why the reaction worked, Schindler’s lab teamed up with the lab of Heather Kulik, associate professor of chemical engineering at the Massachusetts Institute of Technology.
“Someone might show that a new reaction works, but if it only works on a single compound, it is not useful to anyone because pharmaceutical companies are likely wanting to use the reaction on their unique compound,” Parikh said. “What we can do is show that the reaction works on a diverse range of substrates to essentially prove that the reaction is worth the pharmaceutical company’s time to try.”