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Mycotoxin Research

, Volume 34, Issue 2, pp 141–150 | Cite as

Large-scale total synthesis of 13C3-labeled citrinin and its metabolite dihydrocitrinone

  • Dominik Bergmann
  • Florian Hübner
  • Birgit Wibbeling
  • Constantin Daniliuc
  • Benedikt Cramer
  • Hans-Ulrich Humpf
Original Article

Abstract

The analysis of the nephrotoxic mycotoxin citrinin in food, feed, and physiological samples is still challenging. Nowadays, liquid chromatography coupled with mass spectrometry is the method of choice for achieving low limits of detection. But matrix effects can present impairments for this method. Stable isotope dilution analysis can prevent some of these problems. Therefore, a stable isotopically labeled standard of citrinin for use in stable isotope dilution analysis was synthesized on large scale. The improved diastereoselective total synthetic strategy offered the possibility to introduce three 13C-labels in two steps by ortho-toluate anion chemistry. This led to a mass difference of 3 Da, sufficient for preventing spectral overlap. Additionally, a stable isotopically labeled form of dihydrocitrinone, the main urinary metabolite of citrinin, was synthesized with the same mass difference. This was achieved by a sequence of cyclisation, oxidation, deprotection, and carboxylation reactions starting from a protected intermediate of the labeled citrinin synthesis. Thus, this method also offers a complete way to synthesize dihydrocitrinone from citrinin on large scale.

Keywords

Mycotoxin Citrinin Metabolite Dihydrocitrinone Total synthesis Stable isotope 

Notes

Acknowledgements

We thank the NMR department of the Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, for measurement of some 300 MHz NMR spectra. We also thank the Deutsche Forschungsgemeinschaft (DFG) for funding (GRK1143, IRTG Münster-Nagoya).

Compliance with ethical standards

Conflict of interest

None

Supplementary material

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Copyright information

© Society for Mycotoxin Research and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Food ChemistryMünsterGermany
  2. 2.Organisch-Chemisches InstitutMünsterGermany

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