Synthesis of Saponins with Allobetulin and Glycyrrhetic Acid as Aglycones

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, 69451 Weinheim, Germany, 2006)