Discovery of Terpene-Derived Quaternary Ring Compounds Containing an Oxime Moiety as Potential Fungicides.

Terpene-derived quaternary ring compounds with an oxime moiety were designed and prepared to create fungicides from natural products. A preliminary assessment of their antifungal activity against seven common pathogenic fungi was conducted, and the median effective concentration (EC50) values against Rhizoctonia solani were obtained. The effects of compound 6a19 (3-bromothiophene-containing), which had an outstanding EC50 value (1.62 µg/mL), on the morphology, ultrastructure, reactive oxygen species production, mitochondrial membrane potential, nuclear morphology, and defense-related and respiration-related enzyme activities of mycelia were evaluated. The test compound was speculated to obstruct the bio-oxidative process, inhibiting mycelial growth. Compound 6a19 exhibited a satisfactory in vivo control effect on leaf sheath-infected rice plants. After treating rice plants with 50, 100, and 200 µg/mL 6a19, the protective and therapeutic efficacy values were 48.3 and 70.3%, 58.6 and 75.7%, and 69.0 and 81.1%, respectively. Moreover, a linear quantitative structure-activity relationship (R2 = 0.932, F = 61.3, and S2 = 0.020) was established using density functional theory calculations. Four chemical descriptors that were crucial to the antifungal activity were analyzed: the number of occupied electronic levels of atoms, the minimum atomic orbital electronic population, maximum net atom charge for a H atom, and minimum net atomic charge. In overall consideration of experimental results, it was speculated that the target compounds satisfactorily inhibited R. solani by interfering with biological oxidation pathways, which provided an insight into the future intensive and systematic action mechanism. This research is promising for the invention of novel fungicides from natural terpenes with multiple potential targets and satisfactory ecological compatibility.

Taking Advantage of the Renewable Forest Bioresource Turpentine to Prepare α,ß-Unsaturated Compounds as Highly Efficient Fungicidal Candidates.

In a continuous study on the high-value-added exploration of a renewable forest bioresource turpentine in modern organic agriculture, two series of α-pinene derivatives containing amide and α,ß-unsaturated ketone pharmacophores were prepared. Through an in-depth fungicidal activity study, the title compounds presented excellent inhibitory activity against common crop fungi, especially Sclerotinia sclerotiorum, and the notable EC50 values of α,ß-unsaturated compounds 3u (funan containing) and 3v (thiophene containing) were 1.657 and 1.749 µg/mL, respectively. Further physiological and biochemical studies on S. sclerotiorum revealed that compounds 3u and 3v reduced the ergosterol content in the cell membrane and increased the permeability of the cell membrane. In combination with their effect on mycelial morphology, the title compounds might have inhibitory effects on the biosynthesis of ergosterol, which is a paramount component of the target cell membrane. Moreover, quantitative structure-activity relationship (QSAR) and SAR studies revealed that the charge distribution of α,ß-unsaturated carbonyl ketone derivatives played an important role in the observed fungicidal activity. In summary, this study highlights the design and development of novel high-efficacy turpentine-based antifungal agents.