Chemoenzymatic Synthesis of 5,11‐Epoxy‐4‐Hydroxyamoyphane, 4,11‐Epoxy‐5‐Hydroxyamoyphane and Their Structural Reassignment

A chemoenzymatic synthesis of both 4,11‐epoxy‐5‐hydroxyamoyphane ( 1 ) and 5,11‐epoxy‐4‐hydroxyamoyphane ( 2 ) was achieved. The amorpha‐4,11‐diene containing the amorphane skeleton was obtained in 100 mg/L by supplementing prenol/isoprenol to an engineered E. coli harboring the isopentenol utilization pathway and amorpha‐4,11‐diene synthase (ADS). Selective epoxidation and hydration of the two double bonds of amorpha‐4,11‐diene, followed by a biomimetic epoxide ring‐opening process, allowed the synthesis of both 1 and 2 . The structure of 2, containing the tetrahydrofuran ring, was further confirmed by X‐ray crystal diffraction analysis of its para ‐nitrobenzoyl derivative. The structure of the natural product isolated from Fabiana imbricata , originally elucidated as 1 containing a tetrahydropyran ring, was thus revised to 2 .