A synthetic study toward the BCDEF core skeleton of andilesin C is presented. Key elements involved iron-promoted intramolecular perezone-type [5 + 2] cycloaddition to install the BCD ring system simultaneously in a one-step, copper-catalyzed intramolecular cyclopropanation followed by BiCl3-promoted retro-aldol reaction to construct ring E and a one-pot manipulation involving reduction, lactonization, and isomerization to introduce the lactone ring F. We finally synthesized the congested BCDEF ring system of andilesin C, featuring four quaternary centers and two tertiary centers, by following a strategy with a 15-pot reaction and 11 purification operations.