Elsevier

Carbohydrate Research

Volume 344, Issue 11, 27 July 2009, Pages 1340-1346
Carbohydrate Research

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

https://doi.org/10.1016/j.carres.2009.05.016Get rights and content

Abstract

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 abstract

A 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.

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Section snippets

General methods

All chemicals were obtained from chemical suppliers and used without further purification, unless otherwise noted. All reactions were monitored by TLC on precoated Silica-Gel 60 plates F254, and detected by heating with Mostain (500 mL of 10% H2SO4, 25 g of (NH4)6Mo7O24·4H2O, 1 g Ce(SO4)2·4H2O). Products were purified by flash chromatography with Silica Gel 60 (200–400 mesh). NMR spectra were recorded on 300, 400 or 500 MHz NMR equipment, at room temperature for solutions in CDCl3, D2O or CD3OD.

Acknowledgments

We would like to thank JAE-Doc program (R.L.) and Intramural Frontier Projects (200680F0132) from CSIC for financial support.

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