Design, synthesis, bioactivities of novel geranyl 2-alkoxy-substitutedbenzoate as aphid alarm pheromone derivatives

In order to discover aphid behavioral control agents with new structures, 15 novel geranyl 2-alkoxy-substitutedbenzoate aphid alarm pheromone (E)-β-Farnesene (EβF) derivatives were designed and synthesized by using the method of linking active substructures based on the lead compound 3e (geranyl 2-hydroxy-3-methoxybenzoate). The structures of the target compounds were confirmed by ¹H NMR, IR and HRMS. Preliminary bioassay results showed that some target compounds had varied repellent activity against the pea aphid Acyrthosiphon pisum at the dosage of 5 µg. Among them, the compound 6i exhibited the highest repellent proportion of 60.9%, which was not significantly different from that of the lead 3e . The target protein binding experiments showed that some target compounds had good binding activities with the odorant binding proteins of ApisOBP9. Particularly, compound 6i displayed the best binding constant of (4.92±0.18) µmol/L with ApisOBP9. Further molecular docking study revealed that the representative compound 6i had a good binding affinity to the ApisOBP9, wherein it had the similar binding mode with ApisOBP9 like 3e . This study provides important clues for the further structure optimization.