Preparation of glycyrrhetic acid beta-glycosides having beta (1-->2)-linked disaccharides by the use of 2-O-trichloroacetyl-beta-D-pyranosyl chlorides and their cytoprotective effects on hepatic injury in vivo.
Stepwise glycosidation was adopted for the construction of glycyrrhetic acid beta-glycosides (27-30) having beta (1-->2)-linked disaccharides such as 2-O-beta-D-glucuronopyranosyl-beta-D-glucopyranose, 2-O-beta-D-glucuronopyranosyl-beta-D-galactopyranose, 2-O-beta-D-glucopyranosyl-beta-D-glucuronopyranose and 2-O-beta-D-galactopyranosyl-beta-D-glucuronopyranose. In the first glycosidation, 2-O-trichloroacetyl-beta-D-payranosyl chlorides (9-11) were utilized as starting sugar derivatives to react with methyl glycyrrhetinate (5): Glycosidation of 5 with 9 and 10 gave beta- and alpha-monoglycosides (12) and (13), and (15) and (16), respectively. Treatment of the beta-glycosides 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-O-acetyl-alpha-D-glucuronatopyranosyl bromide (20) gave diglycoside derivatives (23) and (24), respectively, and that of 18 with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide (21) and -alpha-D-galactopyranosyl bromide (22) gave diglycoside derivatives (25) and (26), respectively. The removal of the protecting groups of 23-26 gave diglycosides 27-30, respectively, having a beta-D-glucuronopyranose (beta-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 diglycosides 31-33 having only neutral sugar components and naturally occurring glycyrrhizin (34) having two acidic sugar components (beta-D-glcUA).(ABSTRACT TRUNCATED AT 250 WORDS)
Saito
S
S
Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
Sasaki
Y
Y
Kuroda
K
K
Hayashi
Y
Y
Sumita
S
S
Nagamura
Y
Y
Nishida
K
K
Ishiguro
I
I
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006031:Glycosylation; D006034:Glycyrrhetinic Acid; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016339:Spectrometry, Mass, Fast Atom Bombardment
D006027:Glycosides; D006034:Glycyrrhetinic Acid