Synthesis of Enantiopure (S)-Atenolol by Utilization of Lipase-Catalyzed Kinetic Resolution of a Key Intermediate

Int J Mol Sci. 2024 Mar 20;25(6):3497. doi: 10.3390/ijms25063497.


(S)-Atenolol ((S)-2-(4-(2-Hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) has been synthesized in >99% enantiomeric excess (ee) with the use of Candida antarctica lipase B from Syncozymes (Shanghai, China), in a kinetic resolution of the corresponding racemic chlorohydrin. A catalytic amount of base was used in deprotonation of the phenol building block. The enantiopurity of the chlorohydrin building block remained unchanged upon subsequent amination to yield the final drug. All four steps in the synthesis protocol have been optimized compared to previously reported methods, which makes this new protocol more sustainable and in accordance with green chemistry principles. The overall yield of (S)-atenolol was 9.9%, which will be further optimized.

Keywords: Candida antarctica lipase B; Chiralcel OD-H column; base catalysis; enantiopure (S)-atenolol.

MeSH terms

  • Atenolol*
  • Catalysis
  • China
  • Chlorohydrins*
  • Fungal Proteins / metabolism
  • Kinetics
  • Lipase / metabolism
  • Stereoisomerism


  • Atenolol
  • Lipase
  • Fungal Proteins
  • Chlorohydrins

Grants and funding

This research received no external funding.