Biomimetic Total Syntheses of (+)-Chloropupukeananin, (−)-Chloropupukeanolide D, and Chloropestolides

Chloropupukeananin, chloropupukeanolides, and chloropestolides are a family of structurally complex bioactive natural products that possess highly functionalized tricyclo­[4.3.1.03,7]­decane or bicyclo[2.2.2]­octane skeletons. Biosynthesis of the chloropupukeananin family is triggered by the intermolecular heterodimeric Diels–Alder reaction between maldoxin and iso-A82775C; however, the enzymes involved have not yet been identified. We herein report the one-pot biomimetic synthesis of chloropupukeananin and chloropupukeanolide D. Moreover, the effect of the solvent on the intermolecular Diels–Alder reaction of siccayne and maldoxin suggested that the biosynthesis of the chloropupukeananin family involves a Diels–Alderase-catalyzed heterodimeric Diels–Alder reaction.