Abstract: In order to find tetramic acids with high insecticidal activity, the natural product tenuazonic acid (TeA) was used as lead compound, 26 tetramic acid derivatives 4a-4s , 5a-5g , 7a and 8a were designed and synthesized using acyl Meldrum's acid as acylation reagent with different substituted groups of tetramic acids at 3-position and 5-position, in which fourteen target compounds were not reported in the literature. The target compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. The preliminary insecticidal activity eveluation showed that the target compounds had good insecticidal activity against wheat aphids (Macrosiphum avenae (Fabricius)) with systemic action at 100 μg/mL concentration for 72 h. Compounds 5d and 7a showed excellent insecticidal activities with the lethal rate of 100% in 48 h at the concentration of 100 μg/mL, which was higher than that of spirotetramat. 5d and 7a could be used as lead compounds for further research. The residues of 4e , 5c , 7a and 8a in wheat plants showed that the target compounds could be well absorbed. The study may provide a guideline of further studies on for structure-insecticidal activity relationships of tetramic acid derivatives.