Synthesis and quantitative structure–activity relationship (QSAR) study of C7-oxime ester derivatives of obacunone as insecticidal agents

Abstract

As part of our ongoing search for new insecticidal agents originating from natural products, in the present paper, we have prepared a series of C7-oxime ester derivatives of obacunone and evaluated their insecticidal activity at 1 mg mL⁻¹ against the pre-third-instar larvae of oriental armyworm (Mythimna separata Walker), a typical lepidopteran pest. The structures of all target compounds were well characterized by ¹H NMR, HRMS, optical rotation, IR, and mp. More importantly, three key steric structures 3m, 3r, and 3s were unambiguously determined by single-crystal X-ray diffraction. Compounds 3e, 3r, 3s and 3w exhibited more promising insecticidal activity with final mortality rates greater than 60%, when compared with their precursor obacunone and toosendanin (a positive control). For the C7-oxime alkylester series, the appropriate length of the side chain at the C-7 position of C7-oximeobacunone was very important for insecticidal activity; for the C7-oxime arylester series, introduction of the chlorine atom on the phenyl ring at the C-7 position of C7-oximeobacunone could lead to the most potent compounds. According to the QSAR model, five descriptors such as RDF100v, RDF105u, Dm, Mor15m and R1u, were likely to affect the biological activity of these compounds. Among them, the most important one was RDF100v. The correlation coefficient (R²), the cross-validation correlation coefficient (Q²) and the standard deviation error in prediction (SDEP) are 0.891, 0.835 and 0.0358, respectively.