Lipase- and Base Catalyzed Synthesis of Enantiopure β-Blocker (S)-Atenolol

Elisabeth Jacobsen; Mari Bergan Hansen; Anna Lifen Tennfjord; Fredrik Heen Blindheim; Lucas Hugo Yvan Bocquin

doi:10.20944/preprints202402.1059.v1

A peer-reviewed article of this Preprint also exists.

Hansen, M.B.; Tennfjord, A.L.; Blindheim, F.H.; Bocquin, L.H.Y.; Jacobsen, E.E. Synthesis of Enantiopure (S)-Atenolol by Utilization of Lipase-Catalyzed Kinetic Resolution of a Key Intermediate. Int. J. Mol. Sci. 2024, 25, 3497. Hansen, M.B.; Tennfjord, A.L.; Blindheim, F.H.; Bocquin, L.H.Y.; Jacobsen, E.E. Synthesis of Enantiopure (S)-Atenolol by Utilization of Lipase-Catalyzed Kinetic Resolution of a Key Intermediate. Int. J. Mol. Sci. 2024, 25, 3497.

Abstract

(S)-Atenolol ((S)-2-(4-(2-Hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) has been synthesized in >99% ee with use of Candida antarctica lipase B from Syncozymes (Shanghai, China), in a kinetic resolution of the corresponding racemic chlorohydrin. Deprotonation of the starting phenol building block was base catalyzed. The enantiopurity of the chlorohydrin building block remained unchanged upon subsequent amination. 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 compared to previously reported protocols.

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Lipase- and Base Catalyzed Synthesis of Enantiopure β-Blocker (S)-Atenolol

Abstract

Keywords

Subject

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