Chemoenzymatic Protocol for the Synthesis of Enantiopure <i>β</i>-Blocker (<i>S</i>)-Bisoprolol
The <i>β</i>-blocker (<i>S</i>)-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 catal...
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MDPI AG
2022-12-01
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| Series: | Catalysts |
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| Online Access: | https://www.mdpi.com/2073-4344/13/1/54 |
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| author | Lucas Bocquin Elisabeth Egholm Jacobsen |
| author_facet | Lucas Bocquin Elisabeth Egholm Jacobsen |
| author_sort | Lucas Bocquin |
| collection | DOAJ |
| description | The <i>β</i>-blocker (<i>S</i>)-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 <i>Candida antarctica</i> resulted in the <i>R</i>-chlorohydrin in high enantiomeric purity. Reaction of this building block with isopropylamine in methanol gave (<i>S</i>)-bisoprolol, and further reaction with fumaric acid gave (<i>S</i>)-bisoprolol fumarate in 96% ee. Specific rotation value confirmed the absolute configuration of the enantiopure drug. |
| first_indexed | 2024-03-09T13:15:39Z |
| format | Article |
| id | doaj.art-9514243c1ce44a368fd6aa0b4dcacb1b |
| institution | Directory Open Access Journal |
| issn | 2073-4344 |
| language | English |
| last_indexed | 2024-03-09T13:15:39Z |
| publishDate | 2022-12-01 |
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| spelling | doaj.art-9514243c1ce44a368fd6aa0b4dcacb1b2023-11-30T21:36:26ZengMDPI AGCatalysts2073-43442022-12-011315410.3390/catal13010054Chemoenzymatic Protocol for the Synthesis of Enantiopure <i>β</i>-Blocker (<i>S</i>)-BisoprololLucas Bocquin0Elisabeth Egholm Jacobsen1Department of Chemistry, Norwegian University of Science and Technology, Høgskoleringen 5, 7491 Trondheim, NorwayDepartment of Chemistry, Norwegian University of Science and Technology, Høgskoleringen 5, 7491 Trondheim, NorwayThe <i>β</i>-blocker (<i>S</i>)-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 <i>Candida antarctica</i> resulted in the <i>R</i>-chlorohydrin in high enantiomeric purity. Reaction of this building block with isopropylamine in methanol gave (<i>S</i>)-bisoprolol, and further reaction with fumaric acid gave (<i>S</i>)-bisoprolol fumarate in 96% ee. Specific rotation value confirmed the absolute configuration of the enantiopure drug.https://www.mdpi.com/2073-4344/13/1/54(<i>S</i>)-bisoprololenantiopure building blocks<i>Candida antarctica</i> lipase Bchiral chromatography |
| spellingShingle | Lucas Bocquin Elisabeth Egholm Jacobsen Chemoenzymatic Protocol for the Synthesis of Enantiopure <i>β</i>-Blocker (<i>S</i>)-Bisoprolol Catalysts (<i>S</i>)-bisoprolol enantiopure building blocks <i>Candida antarctica</i> lipase B chiral chromatography |
| title | Chemoenzymatic Protocol for the Synthesis of Enantiopure <i>β</i>-Blocker (<i>S</i>)-Bisoprolol |
| title_full | Chemoenzymatic Protocol for the Synthesis of Enantiopure <i>β</i>-Blocker (<i>S</i>)-Bisoprolol |
| title_fullStr | Chemoenzymatic Protocol for the Synthesis of Enantiopure <i>β</i>-Blocker (<i>S</i>)-Bisoprolol |
| title_full_unstemmed | Chemoenzymatic Protocol for the Synthesis of Enantiopure <i>β</i>-Blocker (<i>S</i>)-Bisoprolol |
| title_short | Chemoenzymatic Protocol for the Synthesis of Enantiopure <i>β</i>-Blocker (<i>S</i>)-Bisoprolol |
| title_sort | chemoenzymatic protocol for the synthesis of enantiopure i β i blocker i s i bisoprolol |
| topic | (<i>S</i>)-bisoprolol enantiopure building blocks <i>Candida antarctica</i> lipase B chiral chromatography |
| url | https://www.mdpi.com/2073-4344/13/1/54 |
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