title: Biomimetic synthesis of the calcineurin phosphatase inhibitor dibefurin.
abstract: Dibefurin is a Ci -symmetric natural product that acts as an inhibitor of calcineurin phosphatase. A six-step synthesis of this compound is reported, which features an oxidative dimerization of the aromatic polyketide epicoccine as the key step. Dibefurin is proposed to be related to epicolactone, a complex yet racemic fungal metabolite that has recently been discovered. Attempts to access epicolactone from epicoccine and epicoccone B resulted in an unusual dimer that is formed through a hetero-Diels-Alder reaction of a para-quinone methide with an ortho-quinone.
authors.affiliation: Department of Chemistry and Center for Integrated Protein Science, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13 (F4.086), 81377 Munich (Germany) http://www.cup.uni-muenchen.de/oc/trauner/
authors.forename: Pascal
authors.initials: P
authors.lastname: Ellerbrock
authors.forename: Nicolas
authors.initials: N
authors.lastname: Armanino
authors.forename: Dirk
authors.initials: D
authors.lastname: Trauner
mesh_terms: D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry; D032701:Biomimetics; D061565:Cycloaddition Reaction; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D005658:Fungi / Q000737:chemistry; D008958:Models, Molecular; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors*
chemical_list: D001572:Benzofurans; D004791:Enzyme Inhibitors; C099199:dibefurin; C120817:calcineurin phosphatase; D010744:Phosphoric Monoester Hydrolases
keywords: Diels-Alder reaction; biomimetic synthesis; cascade reactions; immunosuppressants; pyrogallols