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

Autor: Hansen MB; Department of Chemistry, Norwegian University of Science and Technology (NTNU), Høgskoleringen 5, N-7491 Trondheim, Norway., Tennfjord AL; Department of Chemistry, Norwegian University of Science and Technology (NTNU), Høgskoleringen 5, N-7491 Trondheim, Norway., Blindheim FH; Department of Chemistry, Norwegian University of Science and Technology (NTNU), Høgskoleringen 5, N-7491 Trondheim, Norway., Bocquin LHY; Department of Chemistry, Norwegian University of Science and Technology (NTNU), Høgskoleringen 5, N-7491 Trondheim, Norway., Jacobsen EE; Department of Chemistry, Norwegian University of Science and Technology (NTNU), Høgskoleringen 5, N-7491 Trondheim, Norway.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Mar 20; Vol. 25 (6). Date of Electronic Publication: 2024 Mar 20.
DOI: 10.3390/ijms25063497
Abstrakt: ( 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.
Databáze: MEDLINE
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