Versatile skeletal editing strategies upgrade nitrogen compounds into drug building blocks

Two new skeletal editing techniques offer a way to create an array of nitrogen-containing rings. Nitrogen heterocycles are valuable structures in many drug molecules, with the researchers behind the studies saying that these synthetic strategies could help accelerate the discovery of candidate drug compounds.

More than 80% of new small molecule drugs approved by the US Food and Drug Administration between 2013 and 2023 contained nitrogen heterocycles, such as piperidines. Chemists often make such rings through the Beckmann rearrangement, which involves reacting a cyclic oxime with an acid to create an amide. However, this approach suffers from poor regioselectivity, requires harsh reaction conditions to reduce the amide to the amine and only leads to ring expansion.