Synthesis of zearalenone-16-β,D-glucoside and zearalenone-16-sulfate: A tale of protecting resorcylic acid lactones for regiocontrolled conjugation.

Hannes Mikula,Rudolf Krska,Dennis Svatunek,Julia Weber,Christian Hametner,Gerhard Adam,Johannes Fröhlich,Philipp Skrinjar

doi:10.3762/bjoc.10.112

Abstract

The development of a reliable procedure for the synthesis of the 16-glucoside and 16-sulfate of the resorcylic acid lactone (RAL) type compound zearalenone is presented. Different protective group strategies were considered and applied to enable the preparation of glucosides and sulfates that are difficult to access up to now. Acetyl and p-methoxybenzyl protection led to undesired results and were shown to be inappropriate. Finally, triisopropylsilyl-protected zearalenone was successfully used as intermediate for the first synthesis of the corresponding mycotoxin glucoside and sulfate that are highly valuable as reference materials for further studies in the emerging field of masked mycotoxins. Furthermore, high stability was observed for aryl sulfates prepared as tetrabutylammonium salts. Overall, these findings should be applicable for the synthesis of similar RAL type and natural product conjugates.

Highlights

Resorcylic acid lactones (RALs, Figure 1), a compound class of benzannulated macrolides, are pharmacologically active secondary metabolites produced by a variety of different fungal species [1]
Triisopropylsilyl-protected zearalenone was successfully used as intermediate for the first synthesis of the corresponding mycotoxin glucoside and sulfate that are highly valuable as reference materials for further studies in the emerging field of masked mycotoxins
Königs–Knorr glucosylation, which in general is most frequently used for the glucosylation of phenols, using commercially available bromo sugar 13 activated by silver(I) salts or under phase transfer conditions led to complex product mixtures (Scheme 2C)

Summary

Introduction

Resorcylic acid lactones (RALs, Figure 1), a compound class of benzannulated macrolides, are pharmacologically active secondary metabolites produced by a variety of different fungal species [1]. The development of a reliable procedure for the synthesis of the 16-glucoside and 16-sulfate of the resorcylic acid lactone (RAL) type compound zearalenone is presented. Scheme 1: General strategy for the synthesis of RAL-2’-conjugation (Pg: protective group, pGlc: protected glucose moiety, pS: protected sulfate, Glc: β,D-glucoside).

Results

Conclusion