Chemoenzymatic synthesis of (S)-Pindolol using lipases

Abstract A straightforward chemoenzymatic synthesis of ( S )-Pindolol has been developed. The key step involved the enzymatic kinetic resolution of rac- 2-acetoxy-1-(1 H -indol-4-yloxy)-3-chloropropane with lipase from Pseudomonas fluorescens via hydrolytic process to obtain enantiomerically enriched halohydrin ( 2 S )-1-(1 H -indol-4-yloxy)-3-chloro-2-propanol (96% ee ) and (2 R )-2-acetoxy-1-(1 H -indol-4-yloxy)-3-chloropropane (97% ee ). The latter was subjected to a hydrolysis reaction catalyzed by Candida rugosa leading to ( 2 R )-1-(1 H -indol-4-yloxy)-3-chloro-2-propanol (97% ee ), followed by a reaction with isopropylamine, producing ( S )-Pindolol (97% ee ) in quantitative yield.