Chemoenzymatic synthesis of rasagiline mesylate using lipases

Abstract

A straightforward chemoenzymatic synthesis of rasagiline mesylate has been developed. The key steps for the introduction of chirality involved kinetic enzymatic resolution with lipases via acetylation of rac-indanol and an inversion configuration Mitsunobu reaction of the produced (S)-indanol. Immobilized lipase from Thermomyces lanuginosus proved to be a robust biocatalyst in the kinetic resolution, leading to (S)-indanol with high selectivity (e.e.>99%, E>200) in just 15min, at 35°C, in hexane, being reused for ten-times without significant loss of the activity and selectivity.