Synthesis And Biological Activity Of ω-Aminomethyl Longifolene Derivatives

ω-aminomethyl longifolene is a kind of primary amine compound containing longifolene structure and allylamine functional group prepared by Prins reaction,halogenation reaction and Gabriel primary amine synthesis reaction.Its chemical properties are active,and it has good application potential in medicine and pesticide.However,the existing synthesis process has some problems,such as low yield,difficult separation and purification.In addition,the research on the synthesis and biological activity of its derivatives has not been thoroughly carried out,which limits its application and popularization.In order to enhance the biological activity ofω-aminomethyl longifolene and expand its application field,this paper carried out research on the improvement of synthesis process,derivatization and antibacterial and herbicidal activities.The main research contents are as follows:（1）The improved Gabriel synthesis method was used to synthesizeω-chloromethyl longifolene fromω-chloromethyl longifolene.The optimal hydrazide hydrolysis reaction conditions and product separation and purification process were investigated by single factor experiment.The structure of the product was confirmed by HRMS,FT-IR,¹H NMR,¹³C NMR and SC-XRD.（2）The amidation reaction ofω-aminomethyl longifolene with acyl chloride was studied,and a series ofω-aminomethyl longifolene（6a-6l）was synthesized.The structure of the product was confirmed by FT-IR,GC-MS,¹H NMR,¹³C NMR and SC-XRD.The molecular structure of compound 6a-6l was optimized by DFT-B3LYP method and 6-311 G（d,p）,and then molecular dock with the active sites of amino acid residues of Staphylococcus aureus,Escherichia coli and Candida albicans was performed to predict the growth inhibition activity of the tested strains.（3）Usingω-chloromethyl longifolene orω-aminomethyl longifolene as raw materials,study the synthesis technology ofω-dimethylaminomethyl longifolene（7a）;The N-alkylation reaction ofω-chloromethyl longifolene with nitrogen heterocyclic secondary amines was studied to synthesize a series of tertiary amines containing longifolene（7b-7j）.The structure of the products was confirmed by FT-IR,GC-MS,¹H NMR and ¹³C NMR.（4）The acid-base neutralization reaction ofω-aminomethyl longifolene with phenoxyacetic acid commercial herbicides and binary fatty acids was studied,and a series ofω-aminomethyl longifolene carboxylate（8a-8o）was synthesized.The structure of the product was confirmed by FT-IR,¹H NMR and ¹³C NMR.（5）The bacteriostatic activity ofω-aminomethyl longifolene and its derivatives against gram-positive bacteria,Gram-negative bacteria and fungi was studied by 96-well plate method.The relationship between the structure and antibacterial activity of the derivatives was discussed by calculating the minimum inhibitory concentration,inhibitory medium concentration and virulence regression equation.（6）Seed germination culture method was used to study the herbicidal activity ofω-aminomethyl longifolene and its carboxylate on monocotyledon（ryegrass）and dicotyledon（rapeseed）.The relationship between the structure and herbicidal activity of the derivatives was discussed by calculating the minimum inhibitory concentration,inhibitory medium concentration and toxicity regression equation.