Synthesis And Insecticidal/Acaricidal Activities Of N-substituted Matrinic Acids And 14-Formyl-15-Chloromatrine Derivatives

Matrine,a plant secondary metabolite,displays a broad scope of biological properties such as anticancer activity,antiviral activity,insecticidal activity,etc.To further clarify the relationship between their structures and insecticidal/acaricidal activities,four series?including 83 compounds,and 74 new ones?matrine derivatives were designed and synthesized.Their structures were well determined and characterized by ¹H NMR,IR and mp,and the steric configuration of 14 compounds was unambiguously confirmed by single crystal X-ray diffraction analysis.Meanwhile,their insecticidal/acaricidal activities were tested against Mythimna separata Walker and Tetranychus cinnabarinus Boisduva by the leaf disks method and slide-dipping method,respectively.The main results were obtained as follows:?1?By using matrine as a lead compound,ten N-substituted matrinic acids,and fifteen N-substituted matrinic acids-podophyllotoxin esters were synthesized by hydrolyzing its lactam ring.At 1 mg/mL,the final mortality rates?FMR?of compounds Ie,IIc,IIk,IIl,and IIm were 65.5%,69.0%,62.1%,72.4%,69.0%,respectively,and were higher than that of the positive control toosendanin?FMR:44.8%?.Compounds Ih and Ii showed the potent acaricidal activity with the LC₅₀values of 0.2890 and 0.2547 mg/mL,respectively,which were 12 times more potent than matrine(LC₅₀:3.5456 mg/mL).Some N-substituted benzyl/benzenesulfonylmatrinic acids showed the promising insecticidal/acaricidal activities;introduction of the electron-donating group on the N-substituted benzylmatrinic acids was unfavorable to the insecticidal activity;introduction of the electron-donating group on the N-substituted benzyl/benzenesulfonylmatrinic acids was favorable to the acaricidal activity.The carboxyl group was necessary for N-substituted matrinic acids showing acaricidal activity.?2?By using matrine as a lead compound,the key intermediate14-formyl-15-chloromatrine was firstly prepared by Vilsmeier-Hacck reaction;then twelve matrine ether derivatives,14-formyl-15-aryloxy/methoxymatrine and14-aryloxymethylidenylmatrine derivatives,were synthesized.The possible mechanism for phenols reacting with 14-formyl-15-chloromatrine was described.At 1mg/mL,11 compounds showed more potent insecticidal activity than matrine,especially the FMR of compound IIIi was 62.1%,and was higher than that of the positive control toosendanin.Introduction of 14-formyl group on the matrine was favorable to the insecticidal activity.?3?Based on 14-formyl-15-chloromatrine,25 novel 14-oxime ester-15-chloromatrine derivatives were synthesized.At 1 mg/mL,9 compounds showed more potent insecticidal activity than matrine,especially the FMR of compound IVu was 62.1%,and was higher than that of the positive control toosendanin.13compounds showed more potent acaricidal activity than matrine,especially IVf and IVg displayed the excellent acaricidal activity with the LC₅₀0 values of 0.6383 and0.6523 mg/mL,respectively;which were 5 times more potent than matrine?LC50:3.5456 mg/mL?.Oxime esterification of 14-formyl-15-chloromatrine as beneficial to the improvement of the insecticidal/acaricidal activities;introduction of alkyl groups with the long chain on the oxime esters was favorable to the insecticidal/acaricidal activities;introduction of para-substitutent on the phenyl of oxime esters was favorable to the insecticidal activity.?4?Based on 14-formyl-15-chloromatrine,21 novel matrino[14,15,b]quinoline derivatives were synthesized.At 0.5 mg/mL,10 compounds showed more potent acaricidal activity than 14-formyl-15-chloromatrine and matrine.Introduction of the quinoline ring into its C14 and C15 positions was favorable to the acaricidal activity.All in all,in this paper,Vilsmeier reagent was used to modify the lactam ring of matrine,and the key intermediate 14-formyl-15-chloromatrine was prepared.Especially unexpected results were obtained when the phenols having electron-withdrawing substituents,reacted 14-formyl-15-chloromatrine.And the possible reaction mechanism was discussed.Introduction of 14-formyl group on the matrine or oxime esterification of 14-formyl-15-chloromatrine was favorable to the insecticidal activity.The carboxyl was important for N-substituted matrinic acids showing acaricidal activity.The above results will pave the way for further research and development of matrine derivatives as new insecticides/acaricides.