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.