Synthetic Modification and Insecticidal Activity of 4-epi-cis-Dihydroagarofuran Derivatives

• Published in: Journal of agricultural and food chemistry Vol. 72; no. 28; pp. 15552 - 15560
• Main Authors: Wang, Ziyu, Jiang, Wei, Tang, Rong, Liu, Hongxiang, Qian, Hao, Guo, Tao, Zhu, Jianjun, Wu, Wenjun, Xie, Weiqing, Zhang, Jiwen
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 17.07.2024; Amer Chemical Soc
• Subjects: Agricultural and Environmental Chemistry; Agriculture; Agriculture, Multidisciplinary; Chemistry; Chemistry, Applied; Food Science & Technology; Life Sciences & Biomedicine; Physical Sciences; Science & Technology; 3D-QSAR; structure−activity relationship; molecular docking; insecticidal activity; dihydroagarofuran; structure-activityrelationship; CELANGULIN V; ACID; MIDGUT; MYTHIMNA-SEPARATA WALKER
• ISSN: 0021-8561; 1520-5118; 1520-5118
• DOI: 10.1021/acs.jafc.4c01690

To synthesize the fundamental framework of dihydroagarofuran, a novel strategy was devised for constructing the C-ring through a dearomatization reaction using 6-methoxy-1-tetralone as the initial substrate. Subsequently, the dihydroagarofuran skeleton was assembled via two consecutive Michael addition reactions. The conjugated diene and trans-dihydroagarofuran skeleton were modified. The insecticidal activities of 33 compounds against Mythimna separata were evaluated. Compounds 11–5 exhibited an LC50 value of 0.378 mg/mL. The activity exhibited a remarkable 29-fold increase compared to positive control Celangulin V, which was widely recognized as the most renowned natural dihydroagarofuran polyol ester insecticidal active compound. Docking experiments between synthetic compounds and target proteins revealed the shared binding sites with Celangulin V. Structure–activity relationship studies indicated that methyl groups at positions C4 and C10 significantly improved insecticidal activity, while ether groups with linear chains displayed enhanced activity; in particular, the allyl ether group demonstrated optimal efficacy. Furthermore, a three-dimensional quantitative structure–activity relationship model was established to investigate the correlation between the skeletal structure and activity. These research findings provide valuable insights for discovering and developing dihydroagarofuran-like compounds.