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Chemoenzymatic separation of diastereoisomers of silybin
Purchartová, Kateřina ; Stiborová, Marie (advisor) ; Wimmer, Zdeněk (referee)
Silybin is major component of silymarin isolated from seeds of the milk thistle (Silybum marianum). This compound is widely used in human medicine against liver disorders and as a protectant against a number of hepatotoxins. It also exhibits other interesting activities as anticancer and chemoprotective, dermatoprotective and also hypocholesterolemic effects. Natural silybin is a nearly equimolar mixture of two diastereoisomers, silybin A and silybin B, whose analytical separation is quite feasible, but preparative separation is extremely complicated. The aim of this work was to find suitable method leading to separation of both silybin diastereoisomers. A library of hydrolases (lipases, esterases and proteases) was tested for their diastereoisomeric discrimination of the selective alcoholysis of 23-O-acetylsilybins. Novozym 435 (lipase B from Candida antarctica immobilized on acrylic resin) proved to be the most suitable enzyme for the preparative production of both optically pure silybin A and B by enzymatic hydrolysis. Under the optimized conditions, silybin A was obtained in 42 % yield and 97 % purity while silybin B was obtained in 67 % yield and 99 % purity. Covalent modifications of Novozym 435 (acetylation, succinylation, and hydroxyethylamidation), which should lead to improvement of...
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