Biocatalyzed Synthesis and Structural Characterization of Monoglucuronides of Hydroxytyrosol, Tyrosol, Homovanillic Alcohol, and 3‐(4′‐Hydroxyphenyl)propanol

Abstract

Abstract:The biocatalytic synthesis and purification of O-b-d-monoglucuronide conjugates of hydroxytyrosol, tyrosol, homovanillic alcohol, and 3-(4'-hydroxyphenyl)propanol, using porcine liver microsomes, are described here. The glucuronides were synthesized, analyzed and separated by HPLC-UV, identified by HPLC-MS, and their structures unequivocally established by NMR techniques. The outcome of the glucuronidation reaction depends on the structure of the phenolic compounds. Thus, the glucuronidation of hydroxytyrosol, biocatalyzed with porcine liver microsomes, proceeded exclusively on the phenolic hydroxy groups. The regioselectivity was similar to that observed for human and rat liver microsomes, the 4'-hydroxy position being more favorable than the 3'-hydroxy one. In the case of tyrosol, homovanillic alcohol, and hydroxyphenylpropanol, two products were formed during microsomal glucuronidation: a major one, the phenolic O-b-d-glucuronidated derivative and, a minor one, the O-b-d-glucuronidated aliphatic alcohol.

Antioxidant Activities of Hydroxytyrosol Main Metabolites Do Not Contribute to Beneficial Health Effects after Olive Oil Ingestion

“…Previous observations suggesting that radical scavenging activity of glucuronides was higher than that of HOTYR do not agree with the present results (Tuck et al, 2002). The present study made use of well characterized pure compounds (Khymenets et al, 2006), instead of compounds extracted from urine. We believe that this result explains the discrepancies found in a previous report (Tuck et al, 2002).…”

“…, and 4Ј-O-hydroxyphenylpropanol glucuronide (4Ј-O-Gluc-HOPhPr) were synthesized according to a previously described method (Khymenets et al, 2006) (Fig. 1).…”

Hydroxytyrosol and Derivatives: Isolation, Synthesis, and Biological Properties

“…Khymenets et al reported [149] a biocatalytic synthesis of glucuronide conjugates of HT and homovanillic alcohol (4-hydroxy-3-methoxyphenylethanol) using porcine liver microsomes to afford the -D-glucuronopyranosyl derivatives 72-74, depicted in Fig. (5).…”

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

“…Biocatalyzed synthesis of hydroxytyrosol, tyrosol, homovanillic alcohol, and 3-(4 0 -hydroxyphenyl)propanol glucuronides has been developed. 16 However, enzymatic synthesis requires the use of either expensive glucuronyl transferases or liver microsomes followed by a final tedious purification of the mixtures obtained. Finally, to the best of our knowledge, the synthesis of urolithin glucuronic acid metabolites has not been described so far.…”