Synthesis And Preliminary Agricultural Activities Of N-Substituted Matrinic Ester Derivatives

The preliminary research results of our research group showed that matrine had excellent potential for agricultural activities.In order to obtain matrine derivatives with higher application value,this study designed and synthesized three series of derivatives of N-substituted matric acid/alcohol/ester through opening the lactam ring of matrine,and 114target compounds including 113 new compounds（10 new intermediates）were obtained.Their insecticidal activities,acaricidal activities and antibacterial activities were evaluated by methods of leaf disks,slide-dip and mycelial growth,respectively.The main findings were as follows:（1）Using matrine as a lead compound,N-benzyl matric ester compounds Ia-1,and IIa-z,a’-z’,a’’,b’’were synthesized.The results of insecticidal activities showed that compound IIv’exhibited the best activity against Mythimna separata.16 compounds showed much higher mortality rates against Tetranychus cinnabarinus than matrine.Among them,the LC₅₀of compound IIb’’was 0.19 mg/m L,and it was 7.6 times acaricidal activity of matrine.The results of structure-activity relationship analysis were as follows:introduction of the electron-withdrawing groups on the N-benzyl of matrinic can increase the insecticidal activities;the carboxyl groups of matrinic acids were important for the acaricidal activities;The orientation of the ester bond in the structure of the matric ester was essential for acaricidal activity.（2）The matrine was used as a lead compound to prepare a aceti/hexanoic/ferrocenecarboxylic acid（N-benzyl）matrine ester derivatives IIIa-r.The results of acaricidal activities showed that there were 6 compounds with a 72-hour mortality rates of more than 60%against T.cinnabarinus.The effect of different benzyl substitutions on acaricidal activities were regular:N-（2-chlorobenzyl）matrinic esters had better acaricidal activities than other benzyl substituted matrinic esters.The antifungal activity results showed that the antifungal activities against Fusarium graminearum,Fusarium solani and Valsa mali were greatly improved after introducting ferrocene structure.When N-benzyl matrinic alcohol was condensed with carboxly,the antifungal activities were not improved regularly,but were greatly improved when condensed with ferrocenecarboxylic acid.It indicated that the ferrocene structure was indeed vital for the antifungal activities of matrine.（3）Using matrine as a lead compound,we produced N-（5-isoxazolyl）methylene matrine derivatives.The results of insecticidal activities showed that the final lethality rates of 2b and 6a on 3rd instar larvae of M.separata reached 63.0%.The results of acaricidal activity showed that the 72-hours median lethal concentrations(LC₅₀values)of compounds2c,IVe,IVh,IVl,IVm,IVo,IVp,IVw,IVy and IVb’on female mites of T.cinnabarinus were between 0.31 and 0.44 mg/m L.The best compound IVp exhibited a relative toxicity of 5.2 folds that of matrine.The preliminary structure-activity relationship analysis was showed as follows.Although 2a obtained by opening the lactam ring of matrine did not significantly improved the insecticidal activity,but 2b and 6a-c showed higher acivities than 2a when the methyl group on its ester was changed to the ethyl one or introduction of allyl group on the nitrogen atom.Opening the lactam ring of matrine gave 2a-c which showed better acaricidal activities than matrine.The acaricidal activities of derivatives 6a-c,which obtained by introducing allyl group on the nitrogen atom to the compounds 2a-c,were not further improved.It indicated that the presence of the NH bond was more profitable than the allyl group to maintain acaricidal activities.When 6a-c was added to hydroximoyl chlorides,most of the corresponding products showed higher acaricidal activity than 6a-c.It indicated that the presence of allyl group was not suitable for the acaricidal activity.In summary,when the lactam ring of matrine was opened,the insecticidal,acaricidal and antifungal activities of corresponding derivatives could be increased;Introduction of ferrocenyl fragment into matrine could enhance the antifungal activity;among them,compound IIb’’exhibited the best acaricidal activity.