Skeletal edit swaps carbon for nitrogen

A team of researchers led by Mark Levin at the University of Chicago has unveiled a reaction that can perform a C-to-N swap in aromatic molecules that already contain a nitrogen atom, such as quinolines ( Nature 2023, DOI: 10.1038/s41586-023-06613-4 ). This approach, along with another that Levin’s lab unveiled in September, should enable medicinal chemists to make these single-atom substitutions in a swath of common molecules, easing efforts to generate analogs of drug candidates. “This is the problem that I started my lab to tackle,” Levin says. The method is the latest entrant to the growing field of skeletal editing , which aims to add, delete, or swap single atoms within a molecule’s backbone. Such alterations can have a profound effect on a molecule’s biological activity. Swapping out carbon in favor of nitrogen is a common tactic for boosting the potency of pharmaceuticals, but in practice these analogs often