Continuous Diastereomeric Kinetic Resolution—Silybins A and B
The natural diastereomeric mixture of silybins A and B is often used (and considered) as a single flavonolignan isolated from the fruit extract of milk thistle ( Silybum marianum ), silymarin. However, optically pure silybin diastereomers are required for the evaluation of their biological activity....
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ftdoajarticles:oai:doaj.org/article:f1d309fa28434cfdad3643fd86ea6ac3 2023-05-15T14:03:28+02:00 Continuous Diastereomeric Kinetic Resolution—Silybins A and B David Biedermann Martina Hurtová Oldřich Benada Kateřina Valentová Lada Biedermannová Vladimír Křen 2021-09-01T00:00:00Z https://doi.org/10.3390/catal11091106 https://doaj.org/article/f1d309fa28434cfdad3643fd86ea6ac3 EN eng MDPI AG https://www.mdpi.com/2073-4344/11/9/1106 https://doaj.org/toc/2073-4344 doi:10.3390/catal11091106 2073-4344 https://doaj.org/article/f1d309fa28434cfdad3643fd86ea6ac3 Catalysts, Vol 11, Iss 1106, p 1106 (2021) silybin silymarin Silybum marianum milk thistle lipase Novozym 435 Chemical technology TP1-1185 Chemistry QD1-999 article 2021 ftdoajarticles https://doi.org/10.3390/catal11091106 2022-12-31T04:33:20Z The natural diastereomeric mixture of silybins A and B is often used (and considered) as a single flavonolignan isolated from the fruit extract of milk thistle ( Silybum marianum ), silymarin. However, optically pure silybin diastereomers are required for the evaluation of their biological activity. The separation of silybin diastereomers by standard chromatographic methods is not trivial. Preparative chemoenzymatic resolution of silybin diastereomers has been published, but its optimization and scale-up are needed. Here we present a continuous flow reactor for the chemoenzymatic kinetic resolution of silybin diastereomers catalyzed by Candida antarctica lipase B (CALB) immobilized on acrylic resin beads (Novozym ® 435). Temperature, flow rate, and starting material concentration were varied to determine optimal reaction conditions. The variables observed were conversion and diastereomeric ratio. Optimal conditions were chosen to allow kilogram-scale reactions and were determined to be −5 °C, 8 g/L silybin, and a flow rate of 16 mL/min. No significant carrier degradation was observed after approximately 30 cycles (30 days). Under optimal conditions and using a 1000 × 15 mm column, 20 g of silybin per day can be easily processed, yielding 6.7 and 5.6 g of silybin A and silybin B, respectively. Further scale-up depends only on the size of the reactor. Article in Journal/Newspaper Antarc* Antarctica Directory of Open Access Journals: DOAJ Articles Catalysts 11 9 1106 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
silybin silymarin Silybum marianum milk thistle lipase Novozym 435 Chemical technology TP1-1185 Chemistry QD1-999 |
spellingShingle |
silybin silymarin Silybum marianum milk thistle lipase Novozym 435 Chemical technology TP1-1185 Chemistry QD1-999 David Biedermann Martina Hurtová Oldřich Benada Kateřina Valentová Lada Biedermannová Vladimír Křen Continuous Diastereomeric Kinetic Resolution—Silybins A and B |
topic_facet |
silybin silymarin Silybum marianum milk thistle lipase Novozym 435 Chemical technology TP1-1185 Chemistry QD1-999 |
description |
The natural diastereomeric mixture of silybins A and B is often used (and considered) as a single flavonolignan isolated from the fruit extract of milk thistle ( Silybum marianum ), silymarin. However, optically pure silybin diastereomers are required for the evaluation of their biological activity. The separation of silybin diastereomers by standard chromatographic methods is not trivial. Preparative chemoenzymatic resolution of silybin diastereomers has been published, but its optimization and scale-up are needed. Here we present a continuous flow reactor for the chemoenzymatic kinetic resolution of silybin diastereomers catalyzed by Candida antarctica lipase B (CALB) immobilized on acrylic resin beads (Novozym ® 435). Temperature, flow rate, and starting material concentration were varied to determine optimal reaction conditions. The variables observed were conversion and diastereomeric ratio. Optimal conditions were chosen to allow kilogram-scale reactions and were determined to be −5 °C, 8 g/L silybin, and a flow rate of 16 mL/min. No significant carrier degradation was observed after approximately 30 cycles (30 days). Under optimal conditions and using a 1000 × 15 mm column, 20 g of silybin per day can be easily processed, yielding 6.7 and 5.6 g of silybin A and silybin B, respectively. Further scale-up depends only on the size of the reactor. |
format |
Article in Journal/Newspaper |
author |
David Biedermann Martina Hurtová Oldřich Benada Kateřina Valentová Lada Biedermannová Vladimír Křen |
author_facet |
David Biedermann Martina Hurtová Oldřich Benada Kateřina Valentová Lada Biedermannová Vladimír Křen |
author_sort |
David Biedermann |
title |
Continuous Diastereomeric Kinetic Resolution—Silybins A and B |
title_short |
Continuous Diastereomeric Kinetic Resolution—Silybins A and B |
title_full |
Continuous Diastereomeric Kinetic Resolution—Silybins A and B |
title_fullStr |
Continuous Diastereomeric Kinetic Resolution—Silybins A and B |
title_full_unstemmed |
Continuous Diastereomeric Kinetic Resolution—Silybins A and B |
title_sort |
continuous diastereomeric kinetic resolution—silybins a and b |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doi.org/10.3390/catal11091106 https://doaj.org/article/f1d309fa28434cfdad3643fd86ea6ac3 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Catalysts, Vol 11, Iss 1106, p 1106 (2021) |
op_relation |
https://www.mdpi.com/2073-4344/11/9/1106 https://doaj.org/toc/2073-4344 doi:10.3390/catal11091106 2073-4344 https://doaj.org/article/f1d309fa28434cfdad3643fd86ea6ac3 |
op_doi |
https://doi.org/10.3390/catal11091106 |
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Catalysts |
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11 |
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9 |
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1106 |
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1766274153747316736 |