Regiospecific synthesis of quercetin O-β-D-glucosylated and O-β-D-glucuronidated isomers

Quercetin, the polyphenolic compound, which has the highest daily intake, is well known for its protective effects against aging diseases and has received a lot of attention for this reason. Both quercetin 3-O-beta-D-glucuronide and quercetin 3'-O-beta-D-glucuronide are human metabolites, which, together with their regioisomers, are required for biological as well as physical chemistry studies. We present here a novel synthetic route based on the sequential and selective protections of the hydroxyl functions of quercetin allowing selective glycosylation, followed by TEMPO-mediated oxidation to the glucuronide. This methodology enabled us to synthesize the five O-beta-D-glucosides and four O-beta-D-glucuronides of quercetin, including the major human metabolite, quercetin 3-O-beta-D-glucuronide. (C) 2011 Published by Elsevier Ltd.