Biomimetic Total Synthesis of (+)-Chloropupukeananin, (–)-Chloropupukeanolide D, and Chloropestolides

The biomimetic total synthesis of (+)-chloropupukeananin (overall 4.5% yield, 19 steps from pyrone <b>22</b>) and (−)-chloropupukeanolide D via an intermolecular Diels-Alder reaction using (−)-maldoxin and (+)-iso-A82775C and an intramolecular carbonyl-ene reaction has been achieved. Moreover, the biomimetic synthesis of chloropestolides H-K using (−)-maldoxin and siccayne unveiled the solvent effect of the intermolecular Diels-Alder reaction. The origin of the stereoselectivity of the intermolecular Diels-Alder reaction is still elusive; however, the biosynthesis of the chloropupukeananin family should involve enzymes that catalyse the intermolecular Diels-Alder reaction.