Chemists decipher cinchona alkaloid biosynthesis

Cinchona alkaloids have a long and storied history in chemistry. Derived from Cinchona plants, members of the molecular family include the chiral catalyst cinchonidine and quinine, an early antimalarial compound that is extracted from cinchona bark on a large scale to flavor tonic water. But precisely how plants make these complex molecules has been a mystery—until now.Scientists led by Sarah E. O’Connor at the Max Planck Institute for Chemical Ecology and C. Robin Buell at the University of Georgia have identified the genes that are responsible for the biosynthesis of cinchona alkaloids’ distinctive quinoline-quinuclidine scaffold. The discovery could help chemists make cinchona alkaloids and their analogs via metabolic engineering.“Can we make quinine and similar alkaloids in an economically friendly way so that we’re not solely limited to extracting these compounds from cinchona bark?” O’Connor asked during her presentation on the work via video today as part of the Division of Medicinal Chemistry’s Global Virtual Symposium at ACS Spring 2026. The researchers also published their results recently in Nature (2026, DOI: 10.1038/s41586-026-10227-x).O’Connor’s group has a long-standing interest in monoterpene indole alkaloids, a class of molecules that includes the antimalarial quinine, the poison strychnine, and the psychoactive compound ibogaine. Five different plant families make monoterpene indole alkaloids; by comparing their biosynthetic pathways, chemists can study how the plants’ evolution diverged to make wildly different molecules from the compound strictosidine, which is made from tryptamine and secologanin starting materials. “It’s a really fascinating chemical and evolutionary and biochemical question: How can nature start