<jats:title>Abstract</jats:title><jats:p>Four novel oxepin‐containing pyrimidines, namely oxepinamides D–G (<jats:bold>1</jats:bold>–<jats:bold>4</jats:bold>), were isolated from cultures of <jats:italic>Aspergillus puniceus</jats:italic> F02Z‐1744. The structures of <jats:bold>1</jats:bold>–<jats:bold>4</jats:bold> were elucidated by analyzing their spectroscopic data generated by 1D and 2D NMR and MS methods. The configurations of <jats:bold>1</jats:bold> and <jats:bold>2</jats:bold> were established based on single‐crystal X‐ray crystallographic analysis. All four compounds <jats:bold>1</jats:bold>–<jats:bold>4</jats:bold> showed transcriptional activation on Liver X Receptor α (LXRα) with EC<jats:sub>50</jats:sub> values of 10.6, 12.8, 13.6, and 12.1 μ<jats:sc>M</jats:sc>, respectively.