Zearalenone Mimics: Synthesis of (E)-6-(1-Alkenyl)-substituted β-Resorcylic Acid Esters

Abstract

Two versatile strategies for the synthesis of mimics of the Fusarium mycotoxin zearalenone (1) have been developed. Optimized preparation of (E)-6-(1-alkenyl) substituted β-resorcylic acid esters was realized via ortho-directed lithiation of variable substrates combined with allylation/isomerization or via formylation/Schlosser–Wittig olefination using different protective group patterns. Spontaneous decarboxylation of (E)-6-(1-alkenyl) substituted β-resorcylic acids indicated the influence of this substituent on the chemical behavior of these compounds. These mimics were already used for the development of optimized standard protocols for the synthesis of phase II metabolites of ZEN (glucosides, glucuronides), and further applications (i.e., sulfate conjugates) are still under investigation.

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GRAPHICAL ABSTRACT

Keywords:

• Mycotoxin
• ortho-directed lithiation
• β-resorcylic acid ester
• Schlosser–Wittig olefination
• zearalenone