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

• 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

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.