<jats:title>Abstract</jats:title><jats:p>Asperchalasine A (<jats:bold>1</jats:bold>), the first cytochalasan dimer featuring a unique decacyclic 5/6/11/5/5/6/5/11/6/5 ring system consisting of 20 chiral centers, was isolated from the culture broth of <jats:italic>Aspergillus flavipes</jats:italic>. Three biogenetically related intermediates, asperchalasines B–D (<jats:bold>2</jats:bold>–<jats:bold>4</jats:bold>), were also isolated. Their structures, including their absolute configurations, were elucidated using a combination of HRESIMS, NMR, ECD, molecular modeling, and single‐crystal X‐ray diffraction techniques. Compound <jats:bold>1</jats:bold>, which possesses an unprecedented 13‐oxatetracyclo[7.2.1.1<jats:sup>2,5</jats:sup>.0<jats:sup>1,6</jats:sup>]tridec‐8,12‐dione core structure, is the first example of a dimeric cytochalasan alkaloid. The biogenetic pathways of <jats:bold>1</jats:bold>–<jats:bold>4</jats:bold> were described starting from the co‐isolated compounds <jats:bold>5</jats:bold> and <jats:bold>6</jats:bold>. More importantly, <jats:bold>1</jats:bold> induced significant G1‐phase cell cycle arrest by selectively inhibiting cyclin A, CDK2 and CDK6 in cancerous, but not normal, cells, highlighting it as a potentially selective cell cycle regulator against cancer cells.