LC-MS/MS-Guided Discovery of Herbicidal Himeic Acid Derivatives from the <i>Nicotiana tabacum</i>-Derived Fungus <i>Aspergillus japonicus</i> 334

Fungal secondary metabolism yields bioactive metabolites with agricultural potential. In the search for herbicidal lead compounds, nine novel himeic acid derivatives, namely, japonimeic acids A-I (<b>1</b>-<b>9</b>), and three known analogs (<b>10</b>-<b>12</b>) were obtained from the fungus <i>Aspergillus japonicus</i> 334 with the assistance of a molecular networking method. The structures were assigned through spectroscopic analyses and optical rotation comparisons. Compound <b>1</b> possessed an unprecedented (<i>N</i>-methyl)-benzene-1,4-diol-substituted unit, representing the first such himeic acid analog. All compounds were evaluated for herbicidal activities against <i>Eleusine indica</i> and <i>Amaranthus retroflexus</i> seed germination and radicle elongation. Significantly, compound <b>7</b> strongly inhibited the germination of <i>E. indica</i> (IC₅₀ = 211.3 μM) and <i>A. retroflexus</i> (IC₅₀ = 54.3 μM), with IC₅₀ values that were higher than those of the positive control glyphosate (603.6 μM for <i>E. indica</i> and 649.1 μM for <i>A. retroflexus</i>). Structure-activity analysis was performed. This study provided promising natural herbicide templates and expanded the agricultural potential of himeic acid derivatives.