Abstract
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.
Highlights
The natural diastereomeric mixture of silybin A and B is isolated from the crude extract of the fruits of Silybum marianum L.(Asteraceae)
Silybin and its congeners belong to a subclass of flavonoids named flavonolignans [1]
Batch preparation methods capable of providing pure silybinsepaIn this work, we report the use of a multigram flow-chemicalquantities setup for theof diastereomeric silybins A andhave
Summary
The natural diastereomeric mixture of silybin A and B (approximately in the ratio 4:5) is isolated from the crude extract of the fruits (achenes, bot. cypselae) of Silybum marianum L.(Asteraceae). The natural diastereomeric mixture of silybin A and B (approximately in the ratio 4:5) is isolated from the crude extract of the fruits This extract, which contains silybin and other silybin congeners, such as isosilybin, silychristin, and silydianin, as well as some other flavonoids and a polymeric fraction, is called silymarin. Silybin and its congeners belong to a subclass of flavonoids named flavonolignans [1]. They are characterized by a phenylpropanoid moiety fused to the flavan skeleton, often taxifolin. The biosynthesis of flavonolignans in S. marianum is not stereospecific; flavonolignans are typically diastereomeric mixtures (except silydianin). For a detailed review on silybin and other flavonolignans, see ref. For a detailed review on silybin and other flavonolignans, see ref. [2,3,4]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.