Synthesis of the Core Structure of P2X₇ Receptor Antagonists

Significance

P2X₇ receptors on cells of the immune system play an important role in the development and progression of chronic inflammation, neurodegeneration, and chronic pain. The key step in this multikilogram-scale synthesis of a core structure of P2X₇ receptor antagonists (six steps, 22% overall yield) is the methanolytic desymmetrization of the glutaric anhydride derivative D using 2 mol% of the thiourea catalyst E.