Synthesis And Insecticidal Activity Studies Of Tenvermectin Acylated Derivatives

Tenvermectin is a new class of 16-membered macrolide compounds with better activity and lower toxicity with independent intellectual property rights developed by Zhejiang Agriculture and Forestry University and Zhejiang Hisun Pharmaceutical Co.,Ltd.The bioactivity assay showed that the tenvermectin compounds showed superior activity against Plutella xylostella,Tetranychus cinnabarinus and Bursaphelenchus xylophilus,and their toxicity was lower than avermectin,which has the high development value.Therefore,in this paper,the active functional group splicing strategy was used to structurally modify the tenvermectin B C-4" position and the de-glycosyl C-13 and C-4’ positions,and it was expected to have better activity and a wider insecticidal spectrum Compound.The main contents are as follows:Three series of tenvermectin B,tenvermectin B monosaccharide and tenvermectin B agycon which a total of 23 acylated derivatives were synthesized by introducing different acyl groups at the C-13,C-4’ and C-4"sites under the protection of selective C-5 hydroxyl group.All derivatives were characterized by 1H NMR,13C NMR and high resolution mass spectra(HRMS)The tenvermectin B C-13 site has larger steric hindrance than the 4" and 4’ sites,lower activity and lower success rate of acylation reaction.The acylation of tenvermectin B resulted in several derivatives with better biological activity than tenvermectin B.During the study,the tenvermectin B C-4" site acylation reaction also failed due to greater steric hindrance or lower activity leading to acylation.After the C-13 site was reversed,the steric hindrance of the C-13 site was significantly reduced,and the acid chlorides(f,g,h)which did not react with the tenvermectin B aglycon were successfully reacted.To a certain extent,it lays a foundation for improving the hydroxyl reactivity of tenvermectin B C-4"site.The cytotoxic activity of avermectin B acylated derivatives against Plutella xylostella,Bursaphelenchus xylophilus,Tetranychus cinnabarinus was determined respectively by Leaf dipping method by feeding,96-well plate method and leaf dish impregnation method.The results of activity assay showed that all tenvermectin B acylated derivatives insecticidal activity were tested against Plutella xylostella,Tetranychus cinnabarinus and Bursaphelenchus xylophilus.All the tested compounds showed significantin secticidal activity against the above three insect species and the 4"-tenvermectin B derivatives were superior to the 4’-and 13-derivatives of tenvermectin B.Compound 8e displayed potentactivity to Plutella xylostella and Bursaphelenchus xylophilus with LC50 values of 9.2 mg/L and 0.42 mg/L,respectively.Moreover,compound 8b showed the best inhibitory activity to Tetranychus cinnabarinus with LC50 value of 0.0019 mg/L,superior to tenvermectin B.