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

Abstract

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.

Impact of dose on the bioavailability of coffee chlorogenic acids in humans

“…synthesized as described previously. 29 Feruloylglycine and isoferuloylglycine were prepared by methods outlined in an earlier publication. 8…”

Identification of novel circulating coffee metabolites in human plasma by liquid chromatography–mass spectrometry

“…All other available standards (mainly phenolic and chlorogenic metabolites) were synthesized as described previously [19].…”

Absorption and Metabolism of Chlorogenic Acids in Cultured Gastric Epithelial Monolayers

“…Authentic standards of feruloylquinic acids (5-O-FQA, 4-O-FQA, 3-O-FQA); 3-O-and 4-O-glucuronides of caffeic, dihydrocaffeic, dihydroferulic, ferulic, and isoferulic acids; and 3-O-and 4-Or-sulfates of caffeic, dihydrocaffeic, dihydroferulic, ferulic, and isoferulic acids were kindly donated by D. Barron (Nestlé Research Center, Lausanne, Switzerland). All compounds were at least 94% pure (Fumeaux et al, 2010), and presented data have been corrected for purity.…”