<jats:title>Abstract</jats:title><jats:p>Asperflavipines A (<jats:bold>1</jats:bold>) and B (<jats:bold>2</jats:bold>), two structurally complex merocytochalasans, were isolated from <jats:italic>Aspergillus flavipes</jats:italic>. Asperflavipine A (<jats:bold>1</jats:bold>), which contains two cytochalasan moieties and two epicoccine moieties, is the first cytochalasan heterotetramer to be discovered. It is uniquely defined by 5/6/11/5/6/5/6/5/6/5/5/11/6/5 fused tetradecacyclic rings with three continuous bridged ring systems. Asperflavipine B (<jats:bold>2</jats:bold>) is a cytochalasan heterotrimer containing a cytochalasan and two epicoccine moieties with a 5/6/11/5/5/6/5/6/5 nonacyclic ring system. The hypothetical biosynthesis of <jats:bold>1</jats:bold> and <jats:bold>2</jats:bold> is proposed to involve Diels–Alder and [3+2] cycloaddition reactions as key steps and reveals unparalleled plasticity in the biosynthesis of merocytochalasans. The existence of <jats:bold>1</jats:bold> adds a new dimension to the diversity of the cytochalasan family. Compound <jats:bold>1</jats:bold> showed moderate cytotoxicity and induced apoptosis in Jurkat, NB4, and HL60 cells through the activation of caspase‐3 and degradation of poly(ADP‐ribose) polymerase (PARP).