Studies on synthesis and structure-activity relationships against cytoprotective activity of triterpenoidal diglycosides with an acid saccharide, d-glucopyranosuronic acid

Abstract Several triterpenoid α- and β-diglycosides of oleanoic acid ( 1 ), 11-deoxoglycyrrhetic acid ( 4 ) and 11-deoxoglycyrrhetol ( 5 ) were synthesized. The synthetic diglycosides incluced one or both d -glucopyrnanosuronic acids as sugar components. Cytoprotective activities of the diglycosides against carbon tetrachloride-induced hepatotoxicity were investigated using mice. The activities of the synthetic diglycosides were estimated by assay of aspartate transaminase and alanine transaminase, which were released from the injured hepatocytes and compared with that of glycyrrhizin ( 9 ). The β-diglycosides of 1 and 4 showed potent activities in contrast to those of 5 ; none of the α-glycosides showed remarkable activity. Reduction of the carbonyl group (CO) at C-11 on the C-ring of the aglycons slightly enhanced the activity over that of 9 , and replacement of the carboxyl group (COOH) on the aglycons by a hydroxylmethyl group (CH 2 OH) drastically decreased the activity.