LC-MS/MS-Guided Discovery of Herbicidal Himeic Acid Derivatives from the Nicotiana tabacum-Derived Fungus Aspergillus japonicus 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 (1–9), and three known analogs (10–12) were obtained from the fungus Aspergillus japonicus 334 with the assistance of a molecular networking method. The structures were assigned through spectroscopic analyses and optical rotation comparisons. Compound 1 possessed an unprecedented (N-methyl)-benzene-1,4-diol-substituted unit, representing the first such himeic acid analog. All compounds were evaluated for herbicidal activities against Eleusine indica and Amaranthus retroflexus seed germination and radicle elongation. Significantly, compound 7 strongly inhibited the germination of E. indica (IC50 = 211.3 μM) and A. retroflexus (IC50 = 54.3 μM), with IC50 values that were higher than those of the positive control glyphosate (603.6 μM for E. indica and 649.1 μM for A. retroflexus). Structure–activity analysis was performed. This study provided promising natural herbicide templates and expanded the agricultural potential of himeic acid derivatives.