An expeditious synthesis of quercetin 3-O-β-d-glucuronide from rutin

Article abstract of DOI:10.1016/j.tetlet.2011.06.108

We report the synthesis of the major human metabolite of quercetin, quercetin 3-O-β-d-glucuronide, from rutin (quercetin-3-rutinoside), which is commercially available at low cost. This straightforward synthesis is based on the key intermediate 3′,4′,5,7-tetra-O-benzyl-quercetin which is obtained in only two steps by the total benzylation of rutin followed by acid hydrolysis of the rutinoside residue. Glycosylation of the free 3 hydroxyl group by 1-bromo-3,4,6-tetra-O-acetyl-α-d-glucopyranoside yields the protected glucoside. TEMPO-mediated oxidation of primary alcohol on the deprotected glucoside gives access to the benzylated glucuronide. Removal of the benzyl groups which protect the quercetin hydroxyl groups by H₂ (10% Pd/C) yields quercetin 3-O-β-d-glucuronide.