An Enantioselective Synthesis of Prozac

Abstract

The enantioselective synthesis of (S)-Fluoxetine, also known as Prozac^?, is presented. As a selective serotonin reuptake inhibitor, Prozac^? prevents the reabsorption of the neurotransmitter serotonin into the pre-synaptic cell, thereby increasing its extracellular concentration. Low extracellular concentrations of serotonin are known to cause depression, anxiety, and personality disorders. While Prozac^? is marketed as a racemic drug, one of its enantiomers, (S)-fluoxetine, has been proven to exhibit greater physiological activity. Our unique synthetic approach begins with the induction of asymmetry in the achiral starting material with the inexpensive yet powerful enzyme oxynitrilase, which we isolate from commercial grade raw almonds. The crucial palladium-catalyzed chiral shift reaction transfers the stereocenter and introduces necessary functionality, while preserving high levels of enantiopurity.