Succinate dehydrogenase (SDH) present in the inner mitochondrial membrane is an important target enzyme for the design of SDH inhibitor-type fungicides. Using SDH as the target enzyme, 22 novel longifolene-derived diacylhydrazine compounds were designed and synthesized using the renewable natural product longifolene as the starting material. Their structures were confirmed by IR, 1 H NMR, 13 C NMR, electrospray mass spectrometry, and elemental analysis. In vitro antifungal activity of the target compounds was preliminarily evaluated. As a result, some of them showed better or comparable antifungal activity than that of the commercial fungicide chlorothalonil, in which compound 5a had inhibitory rates of 97.5, 80.5, 72.1, and 67.1% against Physalospora piricola , Colletotrichum orbiculare , Alternaria solani, and Gibberella zeae , respectively, presenting excellent and broad-spectrum activity that deserved further study. Besides, a reasonable and effective three-dimensional structure–activity quantitative relationship model has been established. There was a significant positive correlation between the antifungal activity and the docking-based binding energy analyzed using Spearman’s rank correlation algorithm. Also, the simulative binding pattern of the target compounds with SDH was investigated by molecular docking study. Furthermore, the diacylhydrazine and phenol groups of the target compounds were proposed to be the potential pharmacophores by frontier molecular orbital analysis.

In search of novel antifungal agents from natural renewable biomass resources, twenty-two (E)-longifolene-derived tetralone oxime ether compounds were synthesized. Their structures were confirmed by IR, 1 H-NMR, 13 C-NMR, ESI-MS and elemental analysis. The preliminary evaluation of in vitro antifungal activity showed that, at the concentration of 50 μg/ mL, eight target compounds exhibited better antifungal activity than that of the positive control commercial fungicide chlorothalonil against Gibberella zeae, in which compound 5 a held excellent inhibition rate of 85.6 % against Fusarium oxysporum f. sp. Cucumerinu, and compound 5 d displayed a good and broad-spectrum antifungal activity. Furthermore, a preliminary three-dimensional quantitative structure-activity relationship (3D-QSAR) study was carried out by the CoMFA method for the inhibitory activity of the target compounds with aromatic R substituents against G. zeae, and a reasonable and effective 3D-QSAR model (r 2 = 0.992, q 2 = 0.523) was established.