An Environmentally Responsible and Cost-effective Synthesis of the Antimalarial Drug Pyronaridine

Two routes to Pyronaridine are described. The first is a linear sequence that includes a 2-step, 1-pot transformation in an aqueous surfactant medium, enabling an overall yield of 87%. Alternatively, the convergent route utilizes a telescoped 3-step sequence involving an initial neat reaction, followed by two steps performed under aqueous micellar catalysis conditions, producing Pyronaridine in 95% yield. Comparisons to existing literature performed exclusively in organic solvents reveal a five-fold decrease in environmental impact as measured by E Factors.