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Current Organic Synthesis

Editor-in-Chief

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

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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[1]
Wang, Y.Q.; Li, Y.W.; Chen, Q.L.; Liu, Z.H. Long-term exposure of xenoestrogens with environmental relevant concentrations disrupted spermatogenesis of zebrafish through altering sex hormone balance, stimulating germ cell proliferation, meiosis and enhancing apoptosis. Environ. Pollut., 2019, 244, 486-494.
[http://dx.doi.org/10.1016/j.envpol.2018.10.079] [PMID: 30366296]
[2]
Bretveld, R.W.; Thomas, C.M.G.; Scheepers, P.T.J.; Zielhuis, G.A.; Roeleveld, N. Pesticide exposure: The hormonal function of the female reproductive system disrupted? Reprod. Biol. Endocrinol., 2006, 4, 30.
[http://dx.doi.org/10.1186/1477-7827-4-30] [PMID: 16737536]
[3]
Jones, R.D.; Jampani, H.B.; Newman, J.L.; Lee, A.S. Triclosan: A review of effectiveness and safety in health care settings. Am. J. Infect. Control, 2000, 28(2), 184-196.
[http://dx.doi.org/10.1067/mic.2000.102378] [PMID: 10760227]
[4]
United states environmental protection agency (EPA). Reregistration eligibility decision for 2-phenylphenol and salts (orthophenylphenol or opp). Office of prevention, pesticides and toxic substances (7510C). 2006.
[5]
Bedoux, G.; Roig, B.; Thomas, O.; Dupont, V.; Le Bot, B. Occurrence and toxicity of antimicrobial triclosan and by-products in the envi-ronment. Environ. Sci. Pollut. Res. Int., 2012, 19(4), 1044-1065.
[http://dx.doi.org/10.1007/s11356-011-0632-z] [PMID: 22057832]
[6]
Rodricks, J.V.; Swenberg, J.A.; Borzelleca, J.F.; Maronpot, R.R.; Shipp, A.M. Triclosan: A critical review of the experimental data and de-velopment of margins of safety for consumer products. Crit. Rev. Toxicol., 2010, 40(5), 422-484.
[http://dx.doi.org/10.3109/10408441003667514] [PMID: 20377306]
[7]
Bomhard, E.M.; Brendler-Schwaab, S.Y.; Freyberger, A.; Herbold, B.A.; Leser, K.H.; Richter, M. O-phenylphenol and its sodium and po-tassium salts: A toxicological assessment. Crit. Rev. Toxicol., 2002, 32(6), 551-625.
[http://dx.doi.org/10.1080/20024091064318] [PMID: 12487365]
[8]
Guesmi, A.; Sleno, L. In vitro metabolism of triclosan studied by liquid chromatography-high-resolution tandem mass spectrometry. Anal. Bioanal. Chem., 2020, 412(2), 335-342.
[http://dx.doi.org/10.1007/s00216-019-02239-6] [PMID: 31788715]
[9]
Wu, J.; Yue, H.; Zongwei, C. Investigation on metabolism and pharmacokinetics of triclosan in rat plasma by using UPLC-triple quadrupole MS Sepu., 2009, 27, 724-730.
[10]
Moss, T.; Howes, D.; Williams, F.M. Percutaneous penetration and dermal metabolism of triclosan (2,4, 4′-trichloro-2′-hydroxydiphenyl ether). Food Chem. Toxicol., 2000, 38(4), 361-370.
[http://dx.doi.org/10.1016/S0278-6915(99)00164-7] [PMID: 10722890]
[11]
Bartels, M.J.; McNett, D.A.; Timchalk, C.; Mendrala, A.L.; Christenson, W.R.; Sangha, G.K.; Brzak, K.A.; Shabrang, S.N. Comparative me-tabolism of ortho-phenylphenol in mouse, rat and man. Xenobiotica, 1998, 28(6), 579-594.
[http://dx.doi.org/10.1080/004982598239335] [PMID: 9667081]
[12]
Timchalk, C.; Selim, S.; Sangha, G.; Bartels, M.J. The pharmacokinetics and metabolism of 14C/13C-labeled ortho-phenylphenol formation following dermal application to human volunteers. Hum. Exp. Toxicol., 1998, 17(8), 411-417.
[http://dx.doi.org/10.1177/096032719801700801] [PMID: 9756132]
[13]
Brown, R.T.; Scheinmann, F.; Stachulski, A.V. Intermediates for glucuronide synthesis: 7-hydroxycoumarine glucuronide. J. Chem. Res. (S), 1997, 10, 370-371.
[http://dx.doi.org/10.1039/a703397b]
[14]
Wei, Y.; Yoshikai, N. Oxidative cyclization of 2-arylphenols to dibenzofurans under Pd(II)/peroxybenzoate catalysis. Org. Lett., 2011, 13(20), 5504-5507.
[http://dx.doi.org/10.1021/ol202229w] [PMID: 21950683]
[15]
Ranganathan, A.; Gee, S.J.; Hammock, B.D. An immunoassay for the detection of triclosan-O-glucuronide, a primary human urinary me-tabolite of triclosan. Anal. Bioanal. Chem., 2015, 407(24), 7263-7273.
[http://dx.doi.org/10.1007/s00216-015-8918-5] [PMID: 26255293]
[16]
Sancéau, J.Y.; Larouche, D.; Caron, B.; Bélanger, P.; Coquet, A.; Bélanger, A.; Labrie, F.; Gauthier, S. Synthesis and deuterium labelling of the pure selective estrogen receptor modulator (SERM) acolbifene glucuronides. J. Labelled Comp. Radiopharm., 2007, 50, 197-206.
[http://dx.doi.org/10.1002/jlcr.1260]
[17]
Stachulski, A.V.; Meng, X. Glucuronides from metabolites to medicines: A survey of the in vivo generation, chemical synthesis and proper-ties of glucuronides. Nat. Prod. Rep., 1998, 15, 173-186.
[PMID: 9586225]
[18]
Jongkees, S.A.K.; Withers, S.G. Glycoside cleavage by a new mechanism in unsaturated glucuronyl hydrolases. J. Am. Chem. Soc., 2011, 133(48), 19334-19337.
[http://dx.doi.org/10.1021/ja209067v] [PMID: 22047074]
[19]
Kaya, E.; Sonmez, F.; Kucukislamoglu, M.; Nebioglu, M. Selective anomeric deacetylation using zinc acetate as catalyst. Chem. Pap., 2012, 66, 312-315.
[http://dx.doi.org/10.2478/s11696-012-0143-5]
[20]
Provencher, G.; Bérubé, R.; Dumas, P.; Bienvenu, J.F.; Gaudreau, E.; Bélanger, P.; Ayotte, P. Determination of bisphenol A, triclosan and their metabolites in human urine using isotope-dilution liquid chromatography-tandem mass spectrometry. J. Chromatogr. A, 2014, 1348, 97-104.
[http://dx.doi.org/10.1016/j.chroma.2014.04.072] [PMID: 24835763]
[21]
Bérubé, R.; Bélanger, P.; Bienvenu, J.F.; Dumas, P.; Provencher, G.; Gaudreau, É.; Fleury, N. New approach for the determination of ortho-phenylphenol exposure by measurement of sulfate and glucuronide conjugates in urine using liquid chromatography-tandem mass spec-trometry. Anal. Bioanal. Chem., 2018, 410(28), 7275-7284.
[http://dx.doi.org/10.1007/s00216-018-1339-5] [PMID: 30229309]

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