<jats:title>Abstract</jats:title><jats:p>From the culture extracts of the endophytic fungus, <jats:italic>Phoma</jats:italic> sp., isolated from the plant <jats:italic>Salsola oppositifolia</jats:italic>, five secondary metabolites were isolated and characterized. On biomalt agar medium, the strain produced the known substances chrysophanol (<jats:bold>1</jats:bold>) and hypothemycin (<jats:bold>2</jats:bold>), while from liquid‐surface fermentations on a glucose/maltose medium, 2,4‐pyridione derivatives were obtained. Interestingly, one of the isolated compounds, flavipucine (<jats:bold>3a</jats:bold>), showed a positive [<jats:italic>α</jats:italic>]<jats:sub>D</jats:sub>; it, thus, was the enantiomer of the known, but configurationally as yet unassigned (–)‐flavipucine (<jats:bold>3b</jats:bold>). By using quantum‐chemical circular‐dichroism calculations, the absolute configuration of <jats:bold>3a</jats:bold> was established. Moreover, the dihydro analog <jats:bold>5</jats:bold> of flavipucine was isolated for the first time. The stereostructures were determined by extensive spectroscopic data analysis, quantum‐chemical circular dichroism calculations, and X‐ray analysis. With the two enantiomeric side‐chain analogues of flavipucine, fruit rot toxin A (FRT‐A) (<jats:bold>6a</jats:bold>) and the recently published sapinopyridione (<jats:bold>6b</jats:bold>), the family of four naturally occurring substituted 2,4‐pyridiones has become complete. Compound <jats:bold>3a</jats:bold> exhibits antifungal activity against <jats:italic>Phytophthora infestans</jats:italic> and moderate inhibitory activity against gram‐positive and gram‐negative bacteria.