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Current Organic Synthesis

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ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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Research Article

An Improved Synthesis of Glucuronide Metabolites of Hindered Phenolic Xenoestrogens

Author(s): Jean-Yves Sancéau*, Patrick Bélanger, René Maltais and Donald Poirier*

Volume 19, Issue 7, 2022

Published on: 17 June, 2022

Page: [838 - 845] Pages: 8

DOI: 10.2174/1570179419666220426104848

Price: $65

Abstract

Aims and Objective: The syntheses of glucuronide metabolites of phenolic xenoestrogens triclosan and 2-phenylphenol, namely triclosan-O-glucuronide (TCS-G; 1), and 2-phenylphenol-Oglucuronide (OPP-G; 2), were achieved for use as analytical standards.

Methods: Under classical conditions previously reported for glucuronide synthesis, the final basic hydrolysis of the peracylated ester intermediate leading to the free glucuronides is often a limiting step. Indeed, the presence of contaminating by-products resulting from ester elimination has often been observed during this step. This is particularly relevant when the sugar unit is close to a crowded environment as for triclosan and 2-phenylphenol.

Results: To circumvent these problems, we proposed mild conditions for the deprotection of peracetylated glucuronate intermediates.

Conclusion: A new methodology using a key imidate following a two-step protocol for acetates and methyl ester hydrolysis was successfully applied to the preparation of TCS-d3 (1) and OPP-G (2) as well as deuterated isotopomers TCS-d3-G (1-d3) and OPP-d5-G (2-d5).

Keywords: Xenoestrogen, phenol, glucuronide metabolite, deuterium labeling, internal standard, Schmidt’s glucuronidation, zinc acetate transesterification.

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