Biomimetic Synthesis of the Calcineurin Phosphatase Inhibitor Dibefurin

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.