Green Chemo-Enzymatic Protocols for the Synthesis of Enantiopure β -Blockers ( S )-Esmolol and ( S )-Penbutolol
The β -blocker ( S )-esmolol, has been synthesized in 97% enantiomeric excess and 26% total yield in a four-step synthesis, with a transesterification step of the racemic chlorohydrin methyl 3-(4-(3-chloro-2-hydroxypropoxy)phenyl)propanoate, catalysed by lipase B from Candida antarctica from Syncozy...
Published in: | Catalysts |
---|---|
Main Authors: | , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
MDPI AG
2022
|
Subjects: | |
Online Access: | https://doi.org/10.3390/catal12090980 https://doaj.org/article/bbab54645daf483581e182c23fc4b43a |
id |
ftdoajarticles:oai:doaj.org/article:bbab54645daf483581e182c23fc4b43a |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:bbab54645daf483581e182c23fc4b43a 2023-05-15T13:58:18+02:00 Green Chemo-Enzymatic Protocols for the Synthesis of Enantiopure β -Blockers ( S )-Esmolol and ( S )-Penbutolol Susanne Hansen Troøyen Lucas Bocquin Anna Lifen Tennfjord Kristoffer Klungseth Elisabeth Egholm Jacobsen 2022-08-01T00:00:00Z https://doi.org/10.3390/catal12090980 https://doaj.org/article/bbab54645daf483581e182c23fc4b43a EN eng MDPI AG https://www.mdpi.com/2073-4344/12/9/980 https://doaj.org/toc/2073-4344 doi:10.3390/catal12090980 2073-4344 https://doaj.org/article/bbab54645daf483581e182c23fc4b43a Catalysts, Vol 12, Iss 980, p 980 (2022) ( S )-esmolol ( S )-penbutolol enantiopure building blocks characterisation of a dimeric by-product Candida antarctica lipase B chiral chromatography Chemical technology TP1-1185 Chemistry QD1-999 article 2022 ftdoajarticles https://doi.org/10.3390/catal12090980 2022-12-30T20:32:44Z The β -blocker ( S )-esmolol, has been synthesized in 97% enantiomeric excess and 26% total yield in a four-step synthesis, with a transesterification step of the racemic chlorohydrin methyl 3-(4-(3-chloro-2-hydroxypropoxy)phenyl)propanoate, catalysed by lipase B from Candida antarctica from Syncozymes, Shanghai, China. The β -blocker ( S )-penbutolol, has been synthesized in 99% enantiomeric excess and in 22% total yield. The transesterification step of the racemic chlorohydrin 1-chloro-3-(2-cyclopentylphenoxy)propan-2-ol was catalyzed by the same lipase as used for the esmolol building block. We have used different bases for the deprotonation step of the starting phenols, and vinyl butanoate as the acyl donor in the transesterification reactions. The reaction times for the kinetic resolution steps catalysed by the lipase varied from 23 to 48 h, and were run at 30–38 °C. Specific rotation values confirmed the absolute configuration of the enantiopure drugs, however, an earlier report of the specific rotation value of ( S )-esmolol is not consistent with our measured specific rotation values, and we here claim that our data are correct. Compared to the previously reported syntheses of these two enantiopure drugs, we have replaced toluene or dichloromethane with acetonitrile, and replaced the flammable acetyl chloride with lithium chloride. We have also reduced the amount of epichlorohydrin and bases, and identified dimeric byproducts in order to obtain higher yields. Article in Journal/Newspaper Antarc* Antarctica Directory of Open Access Journals: DOAJ Articles Catalysts 12 9 980 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
( S )-esmolol ( S )-penbutolol enantiopure building blocks characterisation of a dimeric by-product Candida antarctica lipase B chiral chromatography Chemical technology TP1-1185 Chemistry QD1-999 |
spellingShingle |
( S )-esmolol ( S )-penbutolol enantiopure building blocks characterisation of a dimeric by-product Candida antarctica lipase B chiral chromatography Chemical technology TP1-1185 Chemistry QD1-999 Susanne Hansen Troøyen Lucas Bocquin Anna Lifen Tennfjord Kristoffer Klungseth Elisabeth Egholm Jacobsen Green Chemo-Enzymatic Protocols for the Synthesis of Enantiopure β -Blockers ( S )-Esmolol and ( S )-Penbutolol |
topic_facet |
( S )-esmolol ( S )-penbutolol enantiopure building blocks characterisation of a dimeric by-product Candida antarctica lipase B chiral chromatography Chemical technology TP1-1185 Chemistry QD1-999 |
description |
The β -blocker ( S )-esmolol, has been synthesized in 97% enantiomeric excess and 26% total yield in a four-step synthesis, with a transesterification step of the racemic chlorohydrin methyl 3-(4-(3-chloro-2-hydroxypropoxy)phenyl)propanoate, catalysed by lipase B from Candida antarctica from Syncozymes, Shanghai, China. The β -blocker ( S )-penbutolol, has been synthesized in 99% enantiomeric excess and in 22% total yield. The transesterification step of the racemic chlorohydrin 1-chloro-3-(2-cyclopentylphenoxy)propan-2-ol was catalyzed by the same lipase as used for the esmolol building block. We have used different bases for the deprotonation step of the starting phenols, and vinyl butanoate as the acyl donor in the transesterification reactions. The reaction times for the kinetic resolution steps catalysed by the lipase varied from 23 to 48 h, and were run at 30–38 °C. Specific rotation values confirmed the absolute configuration of the enantiopure drugs, however, an earlier report of the specific rotation value of ( S )-esmolol is not consistent with our measured specific rotation values, and we here claim that our data are correct. Compared to the previously reported syntheses of these two enantiopure drugs, we have replaced toluene or dichloromethane with acetonitrile, and replaced the flammable acetyl chloride with lithium chloride. We have also reduced the amount of epichlorohydrin and bases, and identified dimeric byproducts in order to obtain higher yields. |
format |
Article in Journal/Newspaper |
author |
Susanne Hansen Troøyen Lucas Bocquin Anna Lifen Tennfjord Kristoffer Klungseth Elisabeth Egholm Jacobsen |
author_facet |
Susanne Hansen Troøyen Lucas Bocquin Anna Lifen Tennfjord Kristoffer Klungseth Elisabeth Egholm Jacobsen |
author_sort |
Susanne Hansen Troøyen |
title |
Green Chemo-Enzymatic Protocols for the Synthesis of Enantiopure β -Blockers ( S )-Esmolol and ( S )-Penbutolol |
title_short |
Green Chemo-Enzymatic Protocols for the Synthesis of Enantiopure β -Blockers ( S )-Esmolol and ( S )-Penbutolol |
title_full |
Green Chemo-Enzymatic Protocols for the Synthesis of Enantiopure β -Blockers ( S )-Esmolol and ( S )-Penbutolol |
title_fullStr |
Green Chemo-Enzymatic Protocols for the Synthesis of Enantiopure β -Blockers ( S )-Esmolol and ( S )-Penbutolol |
title_full_unstemmed |
Green Chemo-Enzymatic Protocols for the Synthesis of Enantiopure β -Blockers ( S )-Esmolol and ( S )-Penbutolol |
title_sort |
green chemo-enzymatic protocols for the synthesis of enantiopure β -blockers ( s )-esmolol and ( s )-penbutolol |
publisher |
MDPI AG |
publishDate |
2022 |
url |
https://doi.org/10.3390/catal12090980 https://doaj.org/article/bbab54645daf483581e182c23fc4b43a |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Catalysts, Vol 12, Iss 980, p 980 (2022) |
op_relation |
https://www.mdpi.com/2073-4344/12/9/980 https://doaj.org/toc/2073-4344 doi:10.3390/catal12090980 2073-4344 https://doaj.org/article/bbab54645daf483581e182c23fc4b43a |
op_doi |
https://doi.org/10.3390/catal12090980 |
container_title |
Catalysts |
container_volume |
12 |
container_issue |
9 |
container_start_page |
980 |
_version_ |
1766266537550807040 |