Synthesis of glycyrrhetic acid diglycosides and their cytoprotective activities against CCl4-induced hepatic injury in vitro

Article abstract of DOI:10.1016/0223-5234(96)89552-3

Glycyrrhetic acid diglycosides 16, 24, 25, 42 and 46, with respectively β-D-glucuronopyranosyl-(1→3)-β-D-glucopyranose, -(1→6)-α-D-glucopyranose, -(1→6)-β-D-glucopyranose, -(1→6)-β-D-galactopyranose, and β-D-galacturonopyranosyl-(→2)-β-D-glucopyranose as sugar components at the O-3 positions on the aglycons, were synthesized. In vitro cytoprotective activities, against CCl₄-induced hepatic injury, of the synthetic diglycosides, methyl β-D-glucuronopyranosyl-(1→4)-α-D-glucopyranosyl-D-glycyrrhe tinate 33 and methyl esters 15 and 23 (the precursors of 16 and 24 respectively) were compared with those of glycyrrhizin 1 and β-D-glucuronopyranosyl-(1→2)-β-D-glucopyranosyl-glycyrrhetic acid 2. Of the glycosides 16, 24, and 25, with β-D-glucuronopyranosylglucopyranose as the sugar component, 16 and 24 were as cytoprotective as 1 and 2, whereas 25 showed no remarkable activity. From stereomodels of the glycosides these differences in activity were inferred to be due to the stereochemistries of the terminal β-D-glucuronopyranoses in the molecules. Glycoside 46, in which the terminal β-D-glucuronopyranose of 2 was replaced by β-D-galacturonopyranose, was as potent as 2. Further, it was confirmed that a free COOH group on the E ring of aglycon was essential for the activity.