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Biomimetic Synthesis of the Calcineurin Phosphatase Inhibitor Dibefurin
Author(s) -
Ellerbrock Pascal,
Armanino Nicolas,
Trauner Dirk
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201407088
Subject(s) - quinone methide , polyketide , calcineurin , chemistry , metabolite , natural product , dimer , quinone , stereochemistry , phosphatase , biochemistry , combinatorial chemistry , enzyme , biosynthesis , organic chemistry , medicine , transplantation , surgery
Abstract Dibefurin is a C i ‐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.