A concise synthesis of glucuronide metabolites of urolithin-B, resveratrol, and hydroxytyrosol

A simple and direct strategy to chemically synthesize O-β-d-glucuronides of urolithin-B 4, resveratrol 5, and the corresponding hydroxytyrosol derivatives 6, 7 (as a regioisomeric mixture), and 8 is described. The critical glycosylation step has been optimized using a structurally simple phenol, urolithin-B, by modification of several reaction parameters (solvent, promoter, and glucuronide donor). Very high yields have been obtained in the first synthesis of the O-β-d-glucuronide of urolithin-B 4. Extension of these reaction conditions was used for the synthesis of resveratrol-3-O-glucuronide 5 where a higher yield than previously reported was obtained by using the much more common trichloroacetimidate glucuronide donor. Finally, three O-β-d-glucuronides of hydroxytyrosol 6, 7, and 8 have been synthesized for the first time using chemical synthesis.

Graphical abstractA simple and direct strategy to chemically synthesize O-β-d-glucuronides of biologically relevant dietary bioactive phenolics: urolithin-B, resveratrol, and hydroxytyrosol is described. The critical glycosylation step has been optimized using a structurally simple phenol, urolithin-B, by modification of different reaction parameters.Figure optionsDownload full-size imageDownload as PowerPoint slide