An Asymmetric Synthesis of Prozac

Abstract

A total enantioselective synthesis of the SSRI (-)-Fluoxetine (Prozac?) is presented. Selective Serotonin Reuptake Inhibitors (SSRIs) work to prevent the reabsorption of serotonin, thus increasing the extracellular concentration of this important neurotransmitter. Low concentrations of serotonin are responsible for a variety of mental disorders, including depression, anxiety, and personality disorders. While Prozac is sold as a racemic drug, it has been shown that one enantiomer is more potent than the other. Our concise synthesis begins with the enzyme oxynitrilase to induce the proper asymmetry in near perfect enantiopurity. The strength of our synthesis lies in its novel use of palladium pi-allyl chemistry to carefully functionalize the molecule while still displaying a high degree of enantiofidelity.