Abstract
Stepwise glycosidation was adopted for the construction of glycyrrhetic acid β-glycosides (27-30) having β(1→2)-linked disaccharides such as 2-O-β-D-flucuronopyranosyl-β-D-glucopyranose, 2-O-β-D-glucuronopyranosyl-β-D-galactopyranose, 2-O-β-D-glucopyranosyl-β-D-glucuronopyranose and 2-O-β-D-galactopyranosyl-β-D-glucuronopyranose. In the first glycosidation, 2-O-trichloroacety-β-D-pyranosyl chlorides (9-11) were utilized as starting sugar derivatives to react with methyl glycyrrhetinate (5) : Glycosidation of 5 with 9 and 10 gave β- and α-monoglycosides (12) and (13), and (15) and (16), respectively. Treatment of the β-glycoside 12 and 15 with ammonia-saturated ether gave products (14) and (17), respectively. The glycosidation of 5 with 11 followed by treatment with ammonia-saturated ether gave compounds (18) and (19), respectively. The second step glycosidations of 14 and 17 with methyl 2, 3, 4-tri-ο-acetyl-α-D-glucuronatopyranosyl bromide (20) gave diglycoside derivatives (23) and (24), respectively, and that of 18 with 2, 3, 4, 6-tetra-O-acetyl-α-D-glucopyranosyl bromide (21) and -α-D-galactopyranosyl bromide (22) gave deglycoside derivatives (25) and (26), respectively. The removal of the protecting groups of 23-26 gave diglycosides 27-30, respectively, having a β-D-glucuronopyranose (β-D-glcUA) as one of two sugar components in the molecules. The cytoprotective effects of the synthesized glycosides 27-30 on carbon tetrachloride (CCl4)-induced hepatotoxicity in vivo were compared with deglycosides 31-33 having only neutral sugar components, and naturally occurring glycyrrhizin (34) having two acidic sugar components (β-D-glcUA). While glycosides 31-33 had no cytoprotective effect, glycosides 27-30 showed potent effects. Especially, 27 and 28, having a β-D-glcUA as the terminal sugar component, were more effective meterials against hepatic injury than glycyrrhizin 34.
