Novel biologically active glycyrrhetinic acid type triterpenes

Abstract

Glycyrrhizin is a triterpenoid saponin found in glycyrrhiza glabra (licorice). It has been reported, among other activities to have antiviral activity (VZV, HIV, Influenza A and B, types 1 and 2 herpes simplex and hepatisis B and C) in vitro and in vivo. Glycyrrhetinic acid is a pentacyclic triterpenoid amyrin derivative obtained from the hydrolysis of glycyrrhizin. The focus of this research was in the following functional group transformations of glycyrrhizin and glycyrrhetinic acid:<br />- Modification of the carboxylic acid group on triterpene skeleton (e.g. by multi-component - UGI reactions, and carbonyl chemistry); - Reactions on hydroxyl group at position C3; and - Modification of carbonyl ketone group at position C11.<br />This research also aimed at developing improved, efficient and high yielding methods for the synthesis of glycyrrhizin and glycyrrhetinic acid derivatives. Some of these syntheses were reproduced in 1-100 g quantities. Natural impurities in technical glycyrrhizin were isolated and characterized. Lastly, the partial synthesis of the natural impurity of isomer of glycyrrhizin, 23-hydroxyglycyrrhetinic acid, was effected on a small scale with the characterization of all intermediates. Structural and analytical characterization of the various synthesized molecules was carried out using 1D- and 2D-NMR and X-ray crystallography. These compounds were prepared for testing as antivirals. Structure activities by relationships were amended by in silico calculations.<br />