Divergent synthesis of conidiogenones B–F and 12β-hydroxyconidiogenone C

Since the initial discovery of conidiogenone in 2002, over 20 highly congested 6/5/5/5-fused cyclopianes have been isolated and have served as an arena for the development of new synthetic strategies. While the D-ring with distinct oxidative decorations serves as a fingerprint region of these natural products, most synthetic approaches focused on the construction of the highly congested tetracyclic structure, and a divergent synthetic approach amenable to D-ring modifications remains unknown. Herein, we describe a synthetic strategy that enabled a divergent synthesis of six conidiogenones, including three first total syntheses. Trimethylenemethane (TMM) diyl-mediated cycloaddition expediently forged the tetracyclic conidiogenone core. The olefin moiety that was formed as a result of the TMM-based cycloaddition served as a synthetic handle for subsequent stereoselective D-ring diversifications.