Design,Synthesis And Bioactivity Studies Of Novel Avermectin B1a Derivatives

Avermectin as an important class of microorganism-derived sixteen-membered macrolactone antibiotics which has the features in terms of high activity,wide spectrum,low toxicity,and safety.It had become a widely useage in agricultural,forestry and efficient biogenic bio-pesticidesinsecticides.However,compare the scale time unfair usage with its own physical and chemical properties of instability the pest resistance and avermectin dosage are increasing,so it is necessary to improve the structural modification of avermectin reasonably.This paper discuss raw material to avermectin C4" bit and the C4' position was derivative synthesis to give compound was 54,and Tetranychus cinnabarinus,Plutella xylostella,Bursaph-elenchus xylophilus as the tested biological activity of the compound was subjected to a measurement system.1.The avermectin C4" position hydroxyl group and a monosaccharide avermectin C4' position hydroxyl group by oxidation,C4''= NH2 synchronous reduction reaction synthesis of 4''-epi-NH2 avermectin B1a(5)and 4'-epi-NH2 avermectin B1a(5)active lead compounds.According to similar synthesis analog synthesis and sub-structure ligation,avermectin synthesized sulfonamide derivatives 34,avermectin series acetamido acid derivative 18,by liquid chromatography-mass spectrometry(LC-MS)and nuclear magnetic resonance spectroscopy(1H NMR)and other methods of characterization and confirmation;Leaf dipping method by feeding,96 method,leaf dipping method respectively Plutella xylostella,Bursaphelenchus xylophilus,Tetranychus cinnabarinus laboratory tests carried out,and SPSS 22.0 to calculate toxicity regression equation of software,LC50 values,95% confidence limits and correlation coefficient.2.Avermectin series sulfonamide derivative of pine wood showed a good insecticidal activity,Tetranychus cinnabarinus,Plutella xylostella showed moderate deviations and biological activity.4''-methyl sulfonamide(methanesulfonamide)avermectin up on the Bursaphelenchus xylophilus active LC50 0.58 mg / L,and quite active avermectin,4''-ethyl sulfonamide avermectin pine nematode activity LC50 was 0.77 mg/L,after the 4''-methyl sulfonamide avermectin.Series sulfonamide deriveatives exhibit similar QSAR in avermectin sulfonamide 6a~6q and monosaccharide avermectin sulfonamide 12a~12q two series,the alkyl chain and heterocycle-substituent group is superior to other compounds,the alkyl chain is not conducive to increasing activity increased,when R1 is a fixed aryl group,the different substituents on the group R2 which is closely related to changes in activity,but no significant law,on the benzene ring containing methyl,ethyl,isopropyl and other electron donating groups activity was significantly higher than other substituted benzene ring containing an electron withdrawing group halogen,nitro,but when the benzene ring having a methoxy,the insecticidal activity was significantly increased.3.Acetyl amino avermectin derivatives series insecticidal,acaricidal activity was significantly higher than the monosaccharide avermectin series acetyl amino acid derivatives of about 2 to 4 times the avermectin C4"-NH2 introduced N-acetyl glycine showed good nematicidal activity against nematodes activity LC50 was 0.78 mg/L,and avermectin quite active amino acid side chains increases,the activity gradually decreased.Description substituent chain length and volume of the substituents affect the size and compound avermectin receptors-glutamic acid chloride ion channel gating binding,when the target compound flexible orientation,configuration and volume balance when,in order to achieve better acaricidal activity.This paper will aim in advancing the design and synthesis of new avermectin derivatives having high insecticidal activity to provide a serial theoretical points and experimental evidences.