Continuous diastereomeric kinetic resolution—silybins a and b

0547149 - MBÚ 2022 RIV CH eng J - Journal Article
Biedermann, David - Hurtová, Martina - Benada, Oldřich - Valentová, Kateřina - Biedermannová, Lada - Křen, Vladimír
Continuous diastereomeric kinetic resolution—silybins a and b.
Catalysts. Roč. 11, č. 9 (2021), č. článku 1106. E-ISSN 2073-4344
R&D Projects: GA MŠMT(CZ) LTC18071; GA ČR GA21-00551S
Institutional support: RVO:61388971 ; RVO:86652036
Keywords : Silybin * Silybum marianum * Silymarin * milk thistle * lipase * Novozym 435 * diastereomers * resolution * flow reaction
OECD category: Organic chemistry; Physical chemistry (BTO-N)
Impact factor: 4.501, year: 2021
Method of publishing: Open access
https://www.mdpi.com/2073-4344/11/9/1106

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.
Permanent Link: http://hdl.handle.net/11104/0323472