An eight-step synthesis of epicolactone reveals its biosynthetic origin.
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.
Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Butenandtstraße 5-13, Munich 81377, Germany.
Pascal
P
Ellerbrock
Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Butenandtstraße 5-13, Munich 81377, Germany.
Nicolas
N
Armanino
Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Butenandtstraße 5-13, Munich 81377, Germany.
Marina K
MK
Ilg
Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Butenandtstraße 5-13, Munich 81377, Germany.
Robert
R
Webster
Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Butenandtstraße 5-13, Munich 81377, Germany.
Dirk
http://orcid.org/0000-0002-6782-6056
D
Trauner
D061565:Cycloaddition Reaction; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry
D007783:Lactones