Structural Modification And Activity Of Avermectins

Avermectins are a kind of antibiotic,biological pesticides with high efficiency,low-toxic,broad-spectrum,safe,environmentally-friend,and widely used in agriculture,forestry and animal husbandry.The trial results showed that these compounds had no activity and absorbability to the eggs of many pests,and with the wide use of avermectins for a long time,some pests had become resistant to them.For this reason,the main direction for the future development of avermectins is to synthesize new compounds by structure modification.The avermectin B2a,one of the main components of avermectins,not only has the activity of avermectin-type compounds,but also has very strong contact toxicity on Animal body surface pests and plants nematodes such as root-knot nematodes,cyst nematodes,root-rot nematodes,pine wood nematodes and stem nematodes.It is a new type of bio-agent for soil nematodemens.At present,the researches on avermectin B2a mainly focus on the fermentation technology and formulation preparation,there is relatively little on the structural transformation.The purpose of this paper is to synthesize new compounds by structural modification of avermectin B2a and evaluate the activity through activity assays.It is expected to provid experimental and theoretical basis for future avermectin B2a derivatization.By analyzing the research progress of avermectins derivatives,we designed the new structure and synthetic route of avermectins derivatives including 4"-deoxy-4"-guanidine substituted avermectin B2a,4"-deoxy-4"-sulfonmethamide substituted aver-mectin B2a,4"-deoxy-4"-thiourea substituted avermectin B2a and 4"-deoxy-4"-phosp-hine substituted avermectin B2a.Avermectin B2a was used as the lead compound to synthesize 2 key intermediates 4"-Oxo-5-O-（allyloxycarbonyl）avermectin B2a and4"-epi-Amino-5-O-（allyloxycarbonyl）-4"-deoxyavermectin B2a by 5-protection,4"-ox-idation and 4"-amine reduction.4"-Oxo-5-O-（allyloxycarbonyl）avermectin B2a was r-eacted with differently substituted hydrazines to generate 6 derivatives and with ph-osphate esters yielded 2 derivatives.4"-epi-Amino-5-O-（allyloxycarbonyl）-4"-deoxya-vermectin B2a underwent 4"-sulfonylation and 5-deprotection to give 4 derivatives.4"-epi-Amino-5-O-（allyloxycarbonyl）-4"-deoxyavermectin B2a underwent 4"-thiourea condensation and 5-deprotection to give 5 derivatives.The synthesized target comp-ounds were characterized by ¹H-NMR,¹³C-NMR and HRMS.The insecticidal activ-ity against Mythimna sepatara,Aphis fabae and Tetranychus urticae was determine-d according to the Pesticide Biological Activity Evaluation SOP.All the tested co-mpounds showed inhibitory activity against the above three insect species.Among t-hem,5d and 10c had the highest activity against Vicia faba,and 10b had highest activity against spider mites than other compounds,so these three compounds coul-d perform further activitie research.