Tiandi Wu, Raghavan Rajagopalan, Kevin D. Moeller
DOI: 10.1016/j.tetlet.2025.155777
Tetrahedron Letters

Nature frequently builds the molecules it uses for communication and the regulation of pathways in cells from common core scaffolds. It is simply more energy efficient for a cell to use the same collection of starting points to make the compounds it needs. With this in mind, medicinal chemists have identified “privileged structures” that mimic one of the common core scaffolds, and in the same way Nature uses the core scaffolds it needs to build the molecules it needs, medicinal chemists use the privileged structure to build new pharmaceuticals that can control pathways in the cell. Because these privileged structures are used frequently, the syntheses employed to construct them have to be efficient and high yielding. In the work presented here, the Moeller group collaborated with a local pharmaceutical company in St. Louis to improve the synthesis of a privileged structure central to their mission by helping them replace a very problematic chemical step in the sequence with a much higher yielding, more selective process using electricity. The result is a better process for building the privileged structure and in turn a better opportunity to build new pharmaceuticals using that core scaffold.