Improved Method for the Synthesis of trans-Feruloyl-β-sitostanol

Abstract

Phytosterols and phytostanols are known to lower low-density lipoprotein−cholesterol (LDL-C) levels in humans by up to 15%, and at least two products, Benecol and Take Control, are now on the market as naturally derived fatty acid esters of phytostanols (stanol esters) and phytosterols (sterol esters), respectively. A synthetic process was developed to synthesize gram quantities of trans-feruloyl-β-sitostanol from ferulic acid and β-sitostanol, with high purity and yields of ∼60%. The process involves (a) condensation of trans-4-O-acetylferulic acid with the appropriate phytostanol or phytostanol mixture in the presence of N,N-dicyclohexylcarbodiimide and 4-(dimethylamino)pyridine, (b) separation of the trans-4-O-acetylferuloyl products by preparative liquid chromatography, (c) selective deacetylation of the feruloyl acetate, and (d) chromatographic purification of the feruloylated phytostanols. The process was successfully applied to synthesize stanol trans-feruloyl esters from “Vegetable Stanols”, a mixture of ∼70:30 β-sitostanol and β-campestanol, in comparable purity and yield. Keywords: β-Sitostanol; trans-feruloyl-β-sitostanol; phytostanols; stanol esters