Discovery of novel skeletons of aphid repellents based on the key fragment of nepetalactone and plant volatiles

Abstract BACKGROUND Aphids are significant agricultural pests, causing extensive crop damage and transmitting plant viruses. Conventional insecticide‐based pest control faces challenges such as human and environmental toxicity and resistance. As alternative solutions, pheromone‐based repellents have emerged as a promising approach. However, the instability of key compounds like ( E )‐β‐Farnesene (EBF) has limited their effectiveness in field applications. To address these limitations, this study focuses on developing novel aphid repellent compounds based on plant volatiles and nepetalactone key fragments. RESULTS In this study, a series of derivatives were designed and synthesized from the lead compound (±)I by incorporating plant volatiles, leading to the discovery of two novel compounds with new skeletons, IV‐13 and IV‐4 . Through further modifications of the ring size and the alkyl substitutions, two optimized structures, compounds IV‐30 and IV‐36 , were identified, demonstrating promising aphid repellent activities. Bioassays indicated that IV‐30 (RV = 85.2%) and IV‐36 (RV = 70.3%) exhibited significantly enhanced repellent properties compared to their precursor compounds. Molecular docking studies revealed strong binding interactions of these compounds with aphid odorant‐binding protein 3(OBP3), providing further evidence of their improved biological efficacy. CONCLUSION The introduction of novel structures such as compounds IV‐30 and IV‐36 based on nepetalactone and plant volatile fragments resulted in the discovery of novel promising para‐pheromones for aphid control. These compounds exhibit stable and effective repellent activities, providing a solid foundation for further development of synthetic aphid repellents in integrated pest management strategies. © 2025 Society of Chemical Industry.