Chemoenzymatic Protocol for the Synthesis of Enantiopure β-Blocker (S)-Bisoprolol

The β-blocker (S)-bisoprolol hemifumarate has been synthesised in 96% enantiomeric excess with 19% total yield in a six-step synthesis. A transesterification reaction of the racemic chlorohydrin 1-chloro-3-(4-((2-isopropoxyethoxy)methyl)phenoxy)propan-2-ol catalysed by lipase B from Candida antarcti...

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Bibliographic Details
Published in:Catalysts
Main Authors: Lucas Bocquin, Elisabeth Egholm Jacobsen
Format: Text
Language:English
Published: Multidisciplinary Digital Publishing Institute 2022
Subjects:
( S )-bisoprolol
enantiopure building blocks
Candida antarctica lipase B
chiral chromatography
Antarc*
Antarctica
Online Access:https://doi.org/10.3390/catal13010054
Description
Summary:The β-blocker (S)-bisoprolol hemifumarate has been synthesised in 96% enantiomeric excess with 19% total yield in a six-step synthesis. A transesterification reaction of the racemic chlorohydrin 1-chloro-3-(4-((2-isopropoxyethoxy)methyl)phenoxy)propan-2-ol catalysed by lipase B from Candida antarctica resulted in the R-chlorohydrin in high enantiomeric purity. Reaction of this building block with isopropylamine in methanol gave (S)-bisoprolol, and further reaction with fumaric acid gave (S)-bisoprolol fumarate in 96% ee. Specific rotation value confirmed the absolute configuration of the enantiopure drug.

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