First Chemical Synthesis and in Vitro Characterization of the Potential Human Metabolites 5-O-Feruloylquinic Acid 4′-Sulfate and 4′-O-Glucuronide

Abstract

Feruloylquinic acids are a major class of biologically active phenolic antioxidants in coffee beans, but their metabolic fate is poorly understood. The present study investigated the phase II metabolism of feruloylquinic acids with selected human sulfotransferases (SULT1A1 and SULT1E1) and uridine 5'-diphosphoglucuronosyltransferases (UGT1A1 and UGT1A9). For unequivocal metabolite identification, the chemical synthesis of two potential human metabolites of 5-O-feruloylquinic acid, the 4'-sulfated and 4'-O-glucuronidated conjugates, has been performed for the first time. Following incubation with human SULT1A1 or SULT1E1, formation of 5-O-feruloylquinic acid 4'-O-sulfate was confirmed by matching its HPLC and MS data with those of the authentic standard. On the other hand, no glucuronide conjugates were detected after incubation with human uridine 5'-diphosphoglucuronosyltransferases. These results suggest that sulfation can take place on the ferulic acid moiety of feruloylquinic acids and may be a major metabolic pathway for feruloylquinic acids in humans.

Synthesis and Evaluation of the Anti-Oxidant Capacity of Curcumin Glucuronides, the Major Curcumin Metabolites

“…First stage was involved in the synthesis of key intermediate methyl [1- O -(4′-formyl-2′-methoxyphenyl)-2,3,4-tri- O -acetyl-β- d -glucopyranosiduronate] ( 4 ) ( Scheme 1 ) by condensing known methyl 1-bromo-2,3,4-tri- O -acetyl-α- d -glucopyranosiduronate ( 2 ) [ 31 , 32 ] with vanillin ( 3 ) in presence of phase transfer catalyst and provided 28% yield. There are few reports [ 21 , 33 ] on the synthesis of same molecule by using either expensive reagents [ 33 ] or by using metal catalyst [ 21 ]. Our approach consists of eco-friendly, inexpensive simple phase transfer condition, which provided a reasonable yield.…”

Dose‐dependent absorption of chlorogenic acids in the small intestine assessed by coffee consumption in ileostomists

“…A 3‐ O ‐FQA‐4′‐ O ‐sulfate has similar product ions ( m/z 193 and m/z 134) as 3‐ O ‐FQA. A 4‐ O ‐FQA‐sulfate has the characteristic m/z 173 product ion similar to 4‐ O ‐FQA . Three FQA‐glucuronides were detected by an [M‐H] − of m/z 543.…”

“…The product ion of m/z 367 indicates the loss of a glucuronic acid unit (176 amu). A 3‐ O ‐FQA‐4′‐ O‐ glucuronide was identified by the product ion m/z 193 similar to 3‐ O ‐FQA, 4‐ O ‐FQA‐4′‐ O ‐glucuronide by the characteristic product ion m/z 173 typical for 4‐FQA and 5‐ O ‐FQA‐4′‐ O ‐glucuronide by the dominating m/z 191 product ion typical for 5‐FQA .…”

Quantification of conjugated metabolites of drugs in biological matrices after the hydrolysis with β‐glucuronidase and sufatase: a review of bio‐analytical methods

“…There are only a few reports on the preparation of conjugated metabolites and their application to quantifications in biological samples. Menozzi-Smarrito et al (2011) reported the synthesis of two potential metabolites of 5-O-feruloylquinic acid, that is, 4 0 -sulfate and 4 0 -O-glucuronide conjugates. The synthetic reference standards were used for the identification of the metabolites of 5-O-feruloylqinic acid in in vitro incubations using human recombinant uridine 5 0 -diphosphoglucuronosyltransferases and sulfotransferases.…”