Synthesis of Isotopically Labeled Fusarium Mycotoxin ^¹³C₂-Moniliformin [1-Hydroxycyclobut-1-ene-3,4-dione]

Abstract

The total synthesis of isotopically labeled [^¹³C₂]-1-hydroxycyclobut-1-ene-3,4-dione (moniliformin) a fungal toxic secondary metabolite to be used as internal standard for mycotoxin analysis is described. The synthesis proceeds in four steps starting from 1,4-dioxane, which was converted to 2,3-dihydro-1,4-dioxine followed by a [2+2]-cycloaddition with trichloroacetyl chloride-1,2-^¹³C₂ as ^¹³C source. The ^¹³C₂-labeled cyclobutanone precursor was transformed to [^¹³C₂]-moniliformin by acid-catalyzed hydrolysis. The successful incorporation of two ^¹³C atoms was proven by detailed NMR and mass spectrometric studies of labeled moniliformin and its precursor.

Fusarium - moniliformin - [2+2] cycloaddition - stable isotope dilution analysis - HPLC-MS/MS

References and Notes

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<A NAME="RD18211ST-17">17</A>

Compound 3 never distilled over separately neither at atmospheric nor at reduced pressure. Distillation was only possible as azeotropic mixture after the addition of H₂O.

<A NAME="RD18211ST-18">18</A>

Purification by continuous liquid-liquid extraction with Et₂O did not give moniliformin in sufficiently pure grade (NMR).