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

( 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 a...

Full description

Bibliographic Details
Published in:International Journal of Molecular Sciences
Main Authors: Mari Bergan Hansen, Anna Lifen Tennfjord, Fredrik Heen Blindheim, Lucas Hugo Yvan Bocquin, Elisabeth Egholm Jacobsen
Format: Article in Journal/Newspaper
Language:English
Published: MDPI AG 2024
Subjects:
enantiopure ( S )-atenolol
Candida antarctica lipase B
base catalysis
Chiralcel OD-H column
Biology (General)
QH301-705.5
Chemistry
QD1-999
Antarc*
Antarctica
Online Access:https://doi.org/10.3390/ijms25063497
https://doaj.org/article/4cae09d68bce4c37b584e8be741a7120
Description
Summary:( 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.

Similar Items