<jats:title>Abstract</jats:title><jats:p>Different culture conditions directed by the OSMAC (one strain‐many compounds) approach drastically modified the metabolites of the fungus <jats:italic>Spicaria elegans</jats:italic>, which yielded the novel spicochalasin A (<jats:bold>1</jats:bold>), five new aspochalasins M–Q (<jats:bold>2</jats:bold>–<jats:bold>6</jats:bold>), and two known aspochalasins (<jats:bold>7</jats:bold> and <jats:bold>8</jats:bold>). The gross structures of <jats:bold>1</jats:bold>–<jats:bold>6</jats:bold> were elucidated by 1D and 2D NMR and MS methods, and their absolute configurations were determined by X‐ray diffraction and the Mosher ester method. Spicochalasin A (<jats:bold>1</jats:bold>) has a unique pentacyclic system and was found to be moderately cytotoxic towards human leukemic HL‐60 cells with an <jats:italic>IC</jats:italic><jats:sub>50</jats:sub> value of 19.9 μ<jats:sc>M</jats:sc>.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)