Is 18 alpha-Glycyrrhizin a real natural product? Improved preparation of 18 alpha-Glycyrrhizin from 18 beta-Glycyrrhizin as a positive standard for HPLC analysis of licorice extracts

18 alpha-Glycyrrhizin is an epimer of 18 beta-glycyrrhizin, a major component of licorice (Glycyrrhiza sp.), which is widely used as a traditional medicine. Whether 18 alpha-glycyrrhizin is a real natural product has been debated in the long history of glycyrrhizin chemistry because 18 beta-glycyrrhizin is epimerizable to a more thermodynamically stable 18 alpha-glycyrrhizin under aqueous alkali conditions. We improved the preparation of 18 alpha-glycyrrhizin from 18 beta-glycyrrhizin by successive epimerization reactions of 18 beta-glycyrrhizin, trimethyl esterification of the resulting epimerized mixture, and alkaline hydrolysis of a purified 18 alpha-glycyrrhizin trimethyl ester. Approaches to the possible presence of 18 alpha-glycyrrhizin in licorice extracts by HPLC using synthetic 18 alpha-glycyrrhizin as a positive standard strongly suggested that 18 alpha-glycyrrhizin could naturally exist as a minor congener of glycyrrhizin derivatives in Glycyrrhiza species. [GRAPHICS] .

Automated summary

This study improved the preparation method of 18α-glycyrrhizin from 18β-glycyrrhizin and provided evidence for the natural existence of 18α-glycyrrhizin in Glycyrrhiza species.