In the search for treatments of type 2 diabetes, scientists have been studying molecules that activate glucokinase. The enzyme catalyzes the first step in the human body’s breakdown of glucose and controls insulin secretion. In 2011, a trio of molecules named tatanans A–C that were purified from a traditional Chinese medicine attracted attention because they appeared to be the first natural products known to activate glucokinase. After completing the total synthesis of the tatanans, a team is now calling the original result into question (Nat. Chem., DOI: 10.1038/nchem.1597). Armen Zakarian and coworkers at the University of California, Santa Barbara, teamed with Brian G. Miller of Florida State University to take on the tatanans. They devised a 13-step route to tatanan A that used consecutive sigmatropic rearrangements to set three adjacent chiral centers. They relied on a different approach to make tatanans B and C. When they repeated the 2011 experiments with human glucokinase and the synthesized tatanans, they saw no enzyme activation. It’s possible that another natural product was the glucokinase activator in the original study, the team speculates, and that it tagged along with the tatanans during isolation from the medicinal plant.