A concise synthesis of glucuronide metabolites of urolithin-B, resveratrol, and hydroxytyrosol.
A simple and direct strategy to chemically synthesize O-beta-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-beta-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-beta-D-glucuronides of hydroxytyrosol 6, 7, and 8 have been synthesized for the first time using chemical synthesis.
Lucas
Ricardo
R
Department of Bioorganic Chemistry, Instituto de Investigaciones Químicas, CSIC-Universidad de Sevilla, 49 Américo Vespucio, 41092 Sevilla, Spain.
Alcantara
David
D
Morales
Juan Carlos
JC
D003374:Coumarins / Q000737:chemistry / Q000378:metabolism*; D020719:Glucuronides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000077185:Resveratrol; D013237:Stereoisomerism; D013267:Stilbenes / Q000737:chemistry / Q000378:metabolism*
D003374:Coumarins; D020719:Glucuronides; D013267:Stilbenes; C005975:3,4-dihydroxyphenylethanol; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D010626:Phenylethyl Alcohol; D000077185:Resveratrol