Biomimetic Synthesis of Chloropupukeananin and its Congeners

Chloropupukeananin was isolated as a natural product with inhibitory activity against HIV-1 replication and antitumor activity. The isolation of its analogues, chloropestolides, chloropupukeanolides, and chlorotheolides, were subsequently reported. These compounds are characterized by highly oxidized multi-functional groups arrayed on a chlorinated bicyclo[2.2.2]octane or tricyclo[4.3.1.03,7]decane skeleton. The biosynthesis of the family of chloropupukeananin natural products starts with intermolecular Diels-Alder reactions using (＋)-iso-A82775C and (−)- maldoxin as precursors. Subsequent carbonyl-ene reactions and other transformations further elaborate the complex structures. These unique chemical structures and biosynthetic pathways have prompted us to initiate synthetic studies. In this manuscript, we will present our synthetic studies of chloropupukeananin and related compounds. © 2024 Society of Synthetic Organic Chemistry. All rights reserved.