Chemo-Enzymatic Synthesis of Enantiopure β-Antagonist (<i>S</i>)-Betaxolol
The β-blocker (<i>S</i>)-betaxolol has been synthesized in 99% enantiomeric excess (<i>ee</i>) from the commercially available precursor 4-(2-hydroxyethyl)phenol. The racemic chlorohydrin 1-chloro-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-ol was esterified with vinyl...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Catalysts |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4344/12/12/1645 |
| Summary: | The β-blocker (<i>S</i>)-betaxolol has been synthesized in 99% enantiomeric excess (<i>ee</i>) from the commercially available precursor 4-(2-hydroxyethyl)phenol. The racemic chlorohydrin 1-chloro-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-ol was esterified with vinyl acetate catalyzed by lipase B from <i>Candida antarctica</i>, which gave the <i>R</i>-chlorhydrin (<i>R</i>)-1-chloro-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-ol in 99% <i>ee</i> with 38% yield. The enantiomeric excess of the <i>R</i>-chlorohydrin was retained in an amination reaction with isopropylamine in methanol to yield (<i>S</i>)-betaxolol in 99% <i>ee</i> and with 9% overall yield. We are under way to improve the yield. |
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| ISSN: | 2073-4344 |