Synthesis of saponins with allobetulin and glycyrrhetic acid as aglycones

Abstract

Procedures for the synthesis of branched Xylβ(1-3)[Galβ(1-2)]Glc and Xylβ(1-3)[Galβ(1-2)]GlcA trisaccharides β-linked to the 3-O moieties of allobetulin and glycyrrhetic acid, respectively, were developed. To this end, β-selective glucosylation of the two triterpenes with a glucosyl donor permitting selective access to 2a-O, 3a-O, and 6a-O, was studied; this led to glucoside intermediates. Xylosylation of the 2a,3a-O-unprotected glucoside was straightforward because, under inverse procedure conditions, exclusively 3a-O-reaction was observed. Subsequent 2a-O-galactosylation followed by 4a,6a-O-debenzylidenation and chemoselective oxidation of the glucose hydroxymethyl group gave the target molecule 1 in high yield after deprotection. The high nucleophilicity of the glycyrrhetinate keto group required a variation in the sequential attachment of the galactosyl and xylosyl residues, so the 2a-O-unprotected glucoside was selected. Initial 2a-O-galactosylation, affording mainly a disaccharide, and subsequent protecting group manipulation and 3a-O-xylosylation gave the target molecule 2b after deprotection. Transformation of the glucose residue in the trisaccharide intermediate into a glucuronate residue furnished target molecule 2a, with the Xylβ(1-3)[Galβ(1-2)] GlcA β-linked to 3-O of the glycyrrhetic acid. © Wiley-VCH Verlag GmbH & Co. KGaA, 2006.