Synthesis of Saponins with Cholestanol, Cholesterol, and Friedelanol as Aglycones

Abstract

AbstractProcedures for the synthesis of branched Xylβ(1→3)[Galβ(1→2)]‐Glc and Xylβ(1→3)[Galβ(1→2)]‐GlcUA trisaccharides β‐linked to the 3‐O of cholesterol, cholestanol, and friedelanol, respectively, were developed. To this end, β‐selective glucosylation of cholesterol with glucosyl donors giving selective access to 2‐O, 3‐O, and 6‐O was studied. This way intermediates 10 and 21 having 2‐O‐acyl, 3‐O‐benzyl and 4,6‐O‐benzylidene or also benzyl protection were obtained. Removal of the 2‐O‐acyl group and then galactosylation afforded β(1→2)‐linked disaccharide intermediates 14 and 23. Standard manipulations with the O‐benzylidene and/or O‐benzyl protecting groups gave selective access to the 3‐O of the glucosyl residue, thus affording with a xylosyl donor the trisaccharide β‐linked to the cholesteryl residue (compound 18) as decisive intermediate. Also an alternative procedure to this compound via attachement of a Xylβ(1→3)Glc residue to cholesterol and then galactosylation could be developed. Total deprotection of 18 or regioselective introduction of a sulfate group and of a dodecylcarbamoyl residue at 6a‐O furnished saponins 34, 36, and 38, respectively. Hydrogenation of cholesteryl disaccharide 23 led directly to a 3a‐O‐unprotected cholestanyl disaccharide 39. β‐Selective xylosylation and transformation of the liberated glucose hydroxymethyl group into a carboxylic group afforded target molecule 1b having the desired Xyl(1→3)[Gal(1→2)]‐GlcUA β‐linked to cholestanol. Similarly, a saponin analog was obtained having an α‐linked L‐rhamnosyl residue instead of the β‐linked D‐xylosyl residue. Application of the glycosylation sequence, as worked out for cholesterol, to friedelanol led to attachment of the Xylβ(1→3)[Galβ(1→2)]‐Glc residue to the 3‐O (compound 54). Complete O‐deacylation led to saponin 55; oxidation of the hydroxymethyl group of the glucose residue to the carboxylic group and then deprotection afforded target molecule 2 containing the same trisaccharide residue as 1b. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)