High Value-Added Application of Natural Products in Crop Protection: Semisynthesis and Acaricidal Activity of Limonoid-Type Derivatives and Investigation of Their Biocompatible O/W Nanoemulsions as Agronanopesticide Candidates.

The increasingly serious resistance of Tetranychus cinnabarinus Boisduval to a wide range of insecticides/acaricides poses a major challenge to their control. The citrus processing industry generates a huge quantity of various wastes that contain many limonoids. To effectively utilize these byproducts and discover more potent green acaricidal molecules as sustainable alternatives for traditional resistant pesticides, various limonoid-type derivatives (halogenated/seven-membered lactam derivatives of obacunone and halogenated/oxime esters/oxime ethers/seven-membered lactam derivatives of limonin) were synthesized based on a diversity-oriented synthetic strategy. The key steric configurations of 10 derivatives were further confirmed by X-ray crystallography. Compound 9m, which displayed greater than 9.7-fold potent acaricidal activity of limonin, was of preeminence. In addition, some interesting structure-activity relationships were observed. Moreover, a biocompatible O/W nanoemulsion delivery system was used to prepare the limonin-based agronanoacaricide, which exhibited pronounced control efficiency against T. cinnabarinus Boisduval in the greenhouse. This systematic investigation will provide valuable information and guidance for future value-added applications of novel eco-friendly natural product-based nanopesticides.

Construction of spiro-1,2,4-oxadiazoline-fused matrine-type alkaloids as pesticidal agents.

In order to increase the agricultural properties of matrine, a series of novel matrine-type alkaloidscontaining spiro-1,2,4-oxadiazoline fragment at the C-15 position were prepared. Eight target molecules were elucidated by X-ray single-crystal diffraction. The antifeedant activities of Ig and IIIh against Mythimna separata Walker were>1.7 folds of the precursor matrine. The acaricidal activities of Ij, IIe, IIg, IIi and IIIa against Tetranychus cinnabarinus Boisduval were 2.6-3.7 folds of matrine. Especially IIg (R1 = R2 = 4-Cl) and IIi (R1 = 4-Cl; R2 = 4-Br) exhibited the pronounced antifeedant and acaricidal activities. SARs showed that their pesticidal activities were related to the substitutents and their positions on the phenyl rings at the C-3 and N-4 positions of 1,2,4-oxadiazoline skeleton.

Agrochemical properties evaluation of some imines alkaloids of matrine/oxymatrine.

To discover non-food renewable forest bioactive products as new potential pesticidal alternatives for crop protection, a series of C15-imines alkaloids were obtained by structural modification of matrine and oxymatrine. Compounds Id, Ih, Ii and IIg (>2-3 folds of their precursors) showed the most potent antifeedant activity against armyworm. Against red spider mite, compounds Ie, Il, IIb, IIc and IIg displayed 1.8-3.1 folds acaricidal activity of their precursors. Notably, compound IIg exhibiting the most pronounced pesticidal activities, can be used as a promising bio-sourced agrochemical agent. The study of stress responses showed that the nAChR subunit α5 and VGSC might be the targets of action of matrine, oxymatrine and IIg against red spider mite.

Synthesis and biological activities of novel pyrazolomatrine derivatives.

In continuation of our program aimed at the development of new natural product-based pesticides, a series of novel pyrazolomatrine derivatives were prepared by structural modifications of matrine, isolated as a quinolizidine alkaloid from the roots of Sophora flave. Their structures were confirmed by 1H NMR, HRMS, etc. Moreover, the steric structures of three compounds were determined by single-crystal X-ray diffraction. Among all derivatives, 19-(naphthyl-2-oyl)pyrazolomatrine (5y) showed 3.13-fold more potent acaricidal activity than its precusor matrine against Tetranychus cinnabarinus; 19-(4-methylbenzoyl)pyrazolomatrine (5j) and 19-(3,5-dimethylbenzoyl)pyrazolomatrine (5k) displayed the promising aphicidal activity against Aphis citricola van der. Their structure-activity relationships were also observed.