Abstract
Epicolactone is a recently isolated fungal metabolite that is highly complex for its size, and yet racemic. With its array of quaternary stereocentres, high degree of functionalization and intricate polycyclic structure, it poses a considerable challenge to synthesis, a challenge that can be met by understanding its biosynthetic origin. If drawn in a certain way, epicolactone reveals a pattern that resembles purpurogallin, the archetype of ubiquitous natural colourants formed via oxidative dimerization. Based on this insight, we designed a biomimetic synthesis of epicolactone that proceeds in only eight steps from vanillyl alcohol. We have isolated a key intermediate that supports our biosynthetic hypothesis and anticipate that an isomer of epicolactone stemming from our synthetic efforts could also be found as a natural product.
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Change history
21 September 2015
In the version of this Article originally published online there was an error in Figure 3. The citation for the five-step synthesis of epicoccine should have read 'ref. 20'. This mistake was introduced in house and has been corrected in all versions of the Article.
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Acknowledgements
We thank the Deutsche Forschungsgemeinschaft (SFB 749) and Center for Integrated Protein Science, Munich for financial support. P.E. gratefully acknowledges the Verband der Chemischen Industrie for a Kekulé Mobility Fellowship. We thank K. Sakata and M. Kojima for experimental assistance. We also thank P. Mayer (LMU Munich) for X-ray analyses.
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D.T. conceived, designed and directed the project and wrote the manuscript with assistance from N.A. and P.E. M.K.I. and R.W. designed and performed experiments in the early phase of the project and P.E. and N.A. designed and performed experiments that led to its successful conclusion.
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Crystallographic data for compound 19 (CIF 903 kb)
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Crystallographic data for compound 20 (CIF 628 kb)
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Crystallographic data for compound 28 (CIF 1488 kb)
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Ellerbrock, P., Armanino, N., Ilg, M. et al. An eight-step synthesis of epicolactone reveals its biosynthetic origin. Nature Chem 7, 879–882 (2015). https://doi.org/10.1038/nchem.2336
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DOI: https://doi.org/10.1038/nchem.2336
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