Chemo-Enzymatic Synthesis of Enantiopure β-Antagonist ( S )-Betaxolol

The β-blocker ( S )-betaxolol has been synthesized in 99% enantiomeric excess ( ee ) 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 fro...

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Bibliographic Details
Published in:Catalysts
Main Authors: Susanne Hansen Troøyen, Elisabeth Egholm Jacobsen
Format: Article in Journal/Newspaper
Language:English
Published: MDPI AG 2022
Subjects:
( S )-betaxolol
enantiopure building blocks
Candida antarctica lipase B
chiral chromatography
Chemical technology
TP1-1185
Chemistry
QD1-999
Antarc*
Antarctica
Online Access:https://doi.org/10.3390/catal12121645
https://doaj.org/article/7c57bfdc357745489ee1dfb413380feb
Description
Summary:The β-blocker ( S )-betaxolol has been synthesized in 99% enantiomeric excess ( ee ) 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 Candida antarctica , which gave the R -chlorhydrin ( R )-1-chloro-3-(4-(2-(cyclopropylmethoxy)ethyl)phenoxy)propan-2-ol in 99% ee with 38% yield. The enantiomeric excess of the R -chlorohydrin was retained in an amination reaction with isopropylamine in methanol to yield ( S )-betaxolol in 99% ee and with 9% overall yield. We are under way to improve the yield.

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