Large-scale separation of silybin diastereoisomers using lipases

Abstract

The flavonolignan silybin ( 1), isolated from the seeds of milk thistle ( Silybum marianum), occurs in nature as an equimolar mixture of two diastereoisomers, silybin A and silybin B, that exhibit different biological activities. The preparative production of optically pure silybin A and B in a diastereoisomeric purity greater than 95% was accomplished using immobilized Candida antarctica lipase B (Novozym 435) in a combination of two reactions: regioselective acetylation of a natural silybin mixture ( 1) and subsequent stereoselective alcoholysis of the resulting 23- O-acetylsilybin ( 2). Several grams of the optically pure substances can be produced within one week using this new, robust and scalable process, which is selective, mild and high-yielding.