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Synfacts 2015; 11(11): 1123
DOI: 10.1055/s-0035-1560736
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of Epicolactone

Contributor(s):
Erick M. Carreira
,
Leonardo J. Nannini
Ellerbrock P, Armanino N, Ilg MK, Webster R, Trauner D * Ludwig Maximilians University of Munich, Germany
An Eight-Step Synthesis of Epicolactone Reveals its Biosynthetic Origin.

Nature Chem. 2015;
DOI: 10.1038/nchem.2336.
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Further Information

Publication History

Publication Date:
19 October 2015 (online)

 
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Key words

(5+2) cycloaddition - retro-Claisen condensation - vinylogous aldol reaction - cascade reaction - biomimetic synthesis

Significance

Trauner and co-workers report the total synthesis of epicolactone, isolated from fungi living on sugar and cocoa trees belonging to the Epicoccum species. Besides the intriguing complexity of the carbon skeleton, this metabolite shows promising antimicrobial and antifungal biological activity. Based on structural similarities with purpurogallin, known to be formed by oxidative dimerization of pyrogallol, they propose the biosynthesis of epicolactone involving an oxidative dimerization of epicoccine and epicoccone B, both metabolites of the Epicoccum species, and support it by means of a highly efficient synthesis.


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Comment

The sequence commences with the synthesis of A, prepared from vanillyl alcohol in six steps (12% overall yield), and epicoccine, prepared from eudesmic acid in five steps (43% overall yield). The exposure of A and epicoccine to K3[Fe(CN)6] generates the respective quinones, which undergo the following reaction cascade: (5+2) cycloaddition gives intermediate C, which undergoes retro-Claisen condensation forming ­intermediate D, followed by vinylogous aldol ­reaction affording E in 42% yield. Epicolactone was obtained by demethylation of E.


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