Synthesis And Insecticidal Activities Of C4/10-oxime Ester Derivatives Of Fraxinellone

Fraxinellone, a degraded limonoid isolated from many species of Meliaceae and Rutaceae plants, exhibits a variety of activities, such as vascular relaxing activity, anti-inflammatory activity, insecticidal activity, and fungicidal activity. Based upon our previous research results, herein a series of new C4/10 oxime ester derivatives of fraxinellone were designed as insecticidal agents. Meanwhile, the preliminary structure-activity relationships(SARs) of fraxinellone derivatives were discussed. The main results were obtained as follows:1. Twenty-four compounds(including four intermediates and twenty C4/10 oxime ester derivatives of fraxinellone) were synthesized by using fraxinellone as a lead compound. Their structures were all characterized by 1H NMR, HRMS, IR, mp, and optical rotation. Among them, twenty-two derivatives were new compounds. The steric configurations of 6i and 7i were confirmed by single crystal X-ray diffraction analysis.2. All compounds exhibited less potent contact activities against Brevicoryne brassicae Linnaeus and the third-instar larvae of Mythimna separata Walker by microspot method at 20 mg/mL. And the stomach activities of all compounds at 20 mg/mL against the third-instar larvae of Plutella xyllostella Linnaeus were also less active when compared with toosendanin. However, some compounds(e.g., 4, 5, 6a-d, 6g, 6j, 7a, and 7k) showed more potent stomach activities than toosendanin against the third-instar larvae of M. separata. The LC50 values of compounds 4, 5, 6a, 6g and 6j were lower than that of fraxinellone. The larvae of M. separata are much sensitive to these compounds.3. By the leaf-dipping method, some compounds at 1mg/mL displayed the growth inhibitory activities against the third-instar larvae of M. separata. Especially compounds 2, 4, 6m, 7b and 7k exhibited the potent insecticidal activities with the final mortality rates about 70%. Moreover, effects of compounds 4 and 6m on the development and growth of the third-instar larvae of M. separata were investigated. And the development and growth of the third-instar larvae of M. separata was delayed by compounds 4 and 6m.4. The preliminary SARs indicated that introduction of the oxime moiety at the C-4/10 position of fraxinellone or introduction of the C-4 oxime esters containing the aliphatic side chain could lead to more potent compounds with stomach activity; introducing the carbonyl or oxime group at the C-4 position of fraxinellone could afford more potent compounds displaying inhibitory development activity. It will pave the way for further structural modification of fraxinellones as insecticidal agents.