Improved method for the synthesis of trans-feruloyl-beta-sitostanol

Phytosterols and phytostanols are known to lower low-density lipoprotein-ch olesterol (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 ester s), respectively. A synthetic process was developed to synthesize gram quan tities of transferuloyl-beta -sitostanol from ferulic acid and beta -sitost anol, with high purity and yields of similar to 60%. The process involves ( a) condensation of trans-4-O-acetylferulic acid with the appropriate phytos tanol or phytostanol mixture in the presence of N,N-dicyclohexylcarbodiimid e and 4-(dimethylamino)pyridine, (b) separation of the trans-4-O-acetylferu loyl products by preparative liquid chromatography, (c) selective deacetyla tion of the feruloyl acetate, and (d) chromatographic purification of the f eruloylated phytostanols. The process was successfully applied to synthesiz e stanol trans-feruloyl esters from "Vegetable Stanols", a mixture of simil ar to 70:30 beta -sitostanol and beta -campestanol, in comparable purity an d yield.