Lipase-Catalyzed Synthesis of the Antidepressant Moclobemide

A chemoenzymatic route is disclosed for the synthesis of the antidepressant drug Moclobemide, a reversible and selective inhibitor of the monoamine oxidase A (MAO-A) enzyme. The reactivities of 4-chlorobenzoic acid and ethyl 4-chlorobenzoate with 4-(2-aminoethyl)morpholine have been studied by using immobilized lipases as biocatalysts in organic media. The optimal reaction conditions were found using a well-known and commercially available lipase, Candida antarctica lipase type B (CAL-B), which efficiently catalyzes the aminolysis reaction of ethyl 4-chlorobenzoate. After CAL-B was identified as the best enzyme for this biotransformation, an optimization study of the reaction conditions was performed, analyzing the influence of different parameters such as ester and amine concentrations, CAL-B loading, organic solvent type, temperature, and reaction time. This has allowed the synthesis of the desired Moclobemide in a high isolated yield (86%) at the gram scale.