Efficient synthesis of glycyrrhetinic acid glycoside/glucuronide derivatives using silver zeolite as promoter

Abstract

3- O -Glycopyranosides of glycyrrhetinic acid have been synthesized in good to high yields and excellent stereoselectivity using glycosyl bromide donors and silver zeolite as promoter. In addition to the preparation of glycosides containing β-linked glucosyl, 2-deoxy-2-trichloroacetamido-glucosyl, galactosyl, cellobiosyl and lactosyl residues, also the deactivated acetylated methyl glucopyranosyluronate bromide donor could be coupled to triterpene aglycon ester derivatives in good yields. The ester protecting group located at C-30 of the oleanolic acid scaffold exerted an influence on the overall yield, with the methylester-protected glycosyl acceptor giving better yields compared to the allyl, benzyl as well as diphenylmethyl ester aglycon. The acetyl-protected glucuronides were differently deblocked in high yields via Zemplén deacetylation or via hydrogenolysis followed by Zemplén deacetylation, and alkaline hydrolysis, respectively, to allow for a selective liberation of the ester groups from either the glucuronide or the glycyrrhetinic acid unit, respectively. The target glycosides/glucuronides serve as probes for pharmaceutical studies aimed at defining structure–activity relationships of glycoside/glucuronide triterpenes.