First synthesis, characterization, and evidence for the presence of hydroxycinnamic acid sulfate and glucuronide conjugates in human biological fluids as a result of coffee consumption

René Fumeaux, Candice Menozzi-Smarrito, Angelique Stalmach, Caroline Munari, Karin Kraehenbuehl, Heike Steiling, Alan Crozier, Gary Williamson, Denis Barron

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A systematic investigation of the human metabolism of hydroxycinnamic acid conjugates was carried out. A set of 24 potential human metabolites of coffee polyphenols has been chemically prepared, and used as analytical standards for unequivocal identifications. These included glucuronide conjugates and sulfate esters of caffeic, ferulic, isoferulic, m-coumaric and p-coumaric acids as well as their dihydro derivatives. A particular focus has been made on caffeic and 3,4-dihydroxyphenylpropionic acid derivatives, especially the sulfate conjugates, for which regioselective preparation was particularly challenging, and have so far never been identified as human metabolites. Ten out of the 24 synthesized conjugates have been identified in human plasma and/or urine after coffee consumption. A number of these conjugates were synthesized, characterized and detected as hydroxycinnamic acid metabolites for the first time. This was the case of dihydroisoferulic acid 3′-O-glucuronide, caffeic acid 3′-sulfate, as well as the sulfate and glucuronide derivatives of 3,4-dihydroxyphenylpropionic acid.

Original languageEnglish
Pages (from-to)5199-5211
Number of pages13
JournalOrganic & Biomolecular Chemistry
Issue number22
Publication statusPublished - 21 Nov 2010
Externally publishedYes

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