Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol
Sustainable methods for producing enantiopure drugs have been developed. Chlorohydrins as building blocks for several β-blockers have been synthesized in high enantiomeric purity by chemo-enzymatic methods. The yield of the chlorohydrins increased by the use of catalytic amount of base. The reason f...
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MDPI AG
2021
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ftdoajarticles:oai:doaj.org/article:e23418b4dc844c919f544d2fd4ff7f69 2023-05-15T13:46:33+02:00 Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol Morten Andre Gundersen Guro Buaas Austli Sigrid Sløgedal Løvland Mari Bergan Hansen Mari Rødseth Elisabeth Egholm Jacobsen 2021-04-01T00:00:00Z https://doi.org/10.3390/catal11040503 https://doaj.org/article/e23418b4dc844c919f544d2fd4ff7f69 EN eng MDPI AG https://www.mdpi.com/2073-4344/11/4/503 https://doaj.org/toc/2073-4344 doi:10.3390/catal11040503 2073-4344 https://doaj.org/article/e23418b4dc844c919f544d2fd4ff7f69 Catalysts, Vol 11, Iss 503, p 503 (2021) ( S )-practolol paracetamol ( S )-pindolol ( S )-carteolol Candida antarctica Lipase B chiral chromatography Chemical technology TP1-1185 Chemistry QD1-999 article 2021 ftdoajarticles https://doi.org/10.3390/catal11040503 2022-12-31T13:48:37Z Sustainable methods for producing enantiopure drugs have been developed. Chlorohydrins as building blocks for several β-blockers have been synthesized in high enantiomeric purity by chemo-enzymatic methods. The yield of the chlorohydrins increased by the use of catalytic amount of base. The reason for this was found to be the reduced formation of the dimeric by-products compared to the use of higher concentration of the base. An overall reduction of reagents and reaction time was also obtained compared to our previously reported data of similar compounds. The enantiomers of the chlorohydrin building blocks were obtained by kinetic resolution of the racemate in transesterification reactions catalyzed by Candida antarctica Lipase B (CALB). Optical rotations confirmed the absolute configuration of the enantiopure drugs. The β-blocker ( S )-practolol (( S )- N -(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) was synthesized with 96% enantiomeric excess ( ee ) from the chlorohydrin ( R )- N -(4-(3-chloro-2 hydroxypropoxy)phenyl)acetamide, which was produced in 97% ee and with 27% yield. Racemic building block 1-((1 H -indol-4-yl)oxy)-3-chloropropan-2-ol for the β-blocker pindolol was produced in 53% yield and ( R )-1-((1 H -indol-4-yl)oxy)-3-chloropropan-2-ol was produced in 92% ee . The chlorohydrin 7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1 H )-one, a building block for a derivative of carteolol was produced in 77% yield. ( R )-7-(3-Chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1 H )-one was obtained in 96% ee . The S -enantiomer of this carteolol derivative was produced in 97% ee in 87% yield. Racemic building block 5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1 H )-one, building block for the drug carteolol, was also produced in 53% yield, with 96% ee of the R -chlorohydrin ( R )-5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1 H )-one. ( S )-Carteolol was produced in 96% ee with low yield, which easily can be improved. Article in Journal/Newspaper Antarc* Antarctica Directory of Open Access Journals: DOAJ Articles Catalysts 11 4 503 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
( S )-practolol paracetamol ( S )-pindolol ( S )-carteolol Candida antarctica Lipase B chiral chromatography Chemical technology TP1-1185 Chemistry QD1-999 |
spellingShingle |
( S )-practolol paracetamol ( S )-pindolol ( S )-carteolol Candida antarctica Lipase B chiral chromatography Chemical technology TP1-1185 Chemistry QD1-999 Morten Andre Gundersen Guro Buaas Austli Sigrid Sløgedal Løvland Mari Bergan Hansen Mari Rødseth Elisabeth Egholm Jacobsen Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol |
topic_facet |
( S )-practolol paracetamol ( S )-pindolol ( S )-carteolol Candida antarctica Lipase B chiral chromatography Chemical technology TP1-1185 Chemistry QD1-999 |
description |
Sustainable methods for producing enantiopure drugs have been developed. Chlorohydrins as building blocks for several β-blockers have been synthesized in high enantiomeric purity by chemo-enzymatic methods. The yield of the chlorohydrins increased by the use of catalytic amount of base. The reason for this was found to be the reduced formation of the dimeric by-products compared to the use of higher concentration of the base. An overall reduction of reagents and reaction time was also obtained compared to our previously reported data of similar compounds. The enantiomers of the chlorohydrin building blocks were obtained by kinetic resolution of the racemate in transesterification reactions catalyzed by Candida antarctica Lipase B (CALB). Optical rotations confirmed the absolute configuration of the enantiopure drugs. The β-blocker ( S )-practolol (( S )- N -(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) was synthesized with 96% enantiomeric excess ( ee ) from the chlorohydrin ( R )- N -(4-(3-chloro-2 hydroxypropoxy)phenyl)acetamide, which was produced in 97% ee and with 27% yield. Racemic building block 1-((1 H -indol-4-yl)oxy)-3-chloropropan-2-ol for the β-blocker pindolol was produced in 53% yield and ( R )-1-((1 H -indol-4-yl)oxy)-3-chloropropan-2-ol was produced in 92% ee . The chlorohydrin 7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1 H )-one, a building block for a derivative of carteolol was produced in 77% yield. ( R )-7-(3-Chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1 H )-one was obtained in 96% ee . The S -enantiomer of this carteolol derivative was produced in 97% ee in 87% yield. Racemic building block 5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1 H )-one, building block for the drug carteolol, was also produced in 53% yield, with 96% ee of the R -chlorohydrin ( R )-5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1 H )-one. ( S )-Carteolol was produced in 96% ee with low yield, which easily can be improved. |
format |
Article in Journal/Newspaper |
author |
Morten Andre Gundersen Guro Buaas Austli Sigrid Sløgedal Løvland Mari Bergan Hansen Mari Rødseth Elisabeth Egholm Jacobsen |
author_facet |
Morten Andre Gundersen Guro Buaas Austli Sigrid Sløgedal Løvland Mari Bergan Hansen Mari Rødseth Elisabeth Egholm Jacobsen |
author_sort |
Morten Andre Gundersen |
title |
Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol |
title_short |
Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol |
title_full |
Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol |
title_fullStr |
Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol |
title_full_unstemmed |
Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol |
title_sort |
lipase catalyzed synthesis of enantiopure precursors and derivatives for β-blockers practolol, pindolol and carteolol |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doi.org/10.3390/catal11040503 https://doaj.org/article/e23418b4dc844c919f544d2fd4ff7f69 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Catalysts, Vol 11, Iss 503, p 503 (2021) |
op_relation |
https://www.mdpi.com/2073-4344/11/4/503 https://doaj.org/toc/2073-4344 doi:10.3390/catal11040503 2073-4344 https://doaj.org/article/e23418b4dc844c919f544d2fd4ff7f69 |
op_doi |
https://doi.org/10.3390/catal11040503 |
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Catalysts |
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11 |
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4 |
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503 |
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1766244102243876864 |