Synthesis And Anti-phytopathogenic Activity Of Flavonoid And Pityriacitrin Alkaloid Derivatives

Green pesticides are important strategic substances related to global grains,foodstuff and ecological safety,which play an important role in the prevention and control of crop pests and diseases and the safeguard of stable food production and increased income.Natural products have become a treasury for the development of medicine and pesticides owing to their novel chemical structure,variety diversity and environmental compatibility,etc.Apart from the direct use of natural product molecules as pesticides,the structural modification and transformation with natural products as the lead was also a method with a high chance of success in obtaining new leads or new green pesticides of biological origin.In this paper,flavonoid derivatives and pityriacitrin alkaloid derivatives were designed and synthesized using the apigenin,a natural product of flavonoid and pityriacitrin alkaloids as the lead compounds,and their anti-phytopathogenic activity was investigated through structural modification and transformation of different sites of core skeleton.The details include the following three parts:Part Ⅰ:The design,synthesis and bactericidal activity of flavonoid derivatives containing oxazine structure.（1）Design and synthesis of flavonoid derivatives containing oxazine structure:By using apigenin,a natural product as the template molecule and preserving the parent nucleus structure,we synthesized flavonoid derivatives by introducing different side chain groups to C-7 of flavonoid and introducing oxazine groups to C-7 and C-8,and investigated the effects of different substituent groups at different structural sites on anti-phytopathogenic activity systematically.（2）The results of fungicidal activity showed that all compounds were tested for fungicidal activity and most of the compounds demonstrated broad-spectrum fungicidal activity against six common plant diseases（Fusarium oxysporium f.sp.cucumeris,Cercospora arachidicola hori,Physalospora piricola,Rhizoctonia cerealis,Pyricularia grisea and Sclerotinia sclerotiorum）at 50μg/L.Most of the compounds had more than 50%inhibitory effect on Physalospora piricola and Sclerotinia sclerotiorum.Among them,the inhibition rates of compounds II-6c,II-7b and II-7i on Physalospora piricola reached 85%,80%and 91%respectively,which can be further investigated as potential anti-phytopathogenic bactericide.（3）A study on structure-activity relationship found that the phenolic hydroxyl group at C-7 had little effect on fungicidal activity,and the introduction of oxazine structure can help improve the fungicidal activity of flavonoids.When benzyl and phenylethyl were introduced to the oxazine structure N,the inhibitory activity of compounds containing electron-attracting groups on the benzene ring was generally higher than that of compounds containing electron-donating groups on the benzene ring.In addition,the position of substituent group on the benzene ring also had an influence on fungicidal activity.Part Ⅱ:Design and synthesis of flavonoid derivatives containing amide structure and their fungicidal activity.（1）Design and synthesis of flavonoid derivatives containing amide structure.Combined with the research group’s previous experience in the application of amino acid compounds in anti-phytopathogenic activity,flavonoid derivatives containing amide structure were designed and synthesized by introducing amino acid fragments to the parent nucleus of apigenin using an active substructure splicing strategy,with apigenin as the lead compound.（2）The results of fungicidal activity showed that all compounds were tested for fungicidal activity and most of the compounds showed certain fungicidal activity against six common plant pathogens at 50μg/L.Most of the compounds had more than 50%inhibitory effect on Sclerotinia sclerotiorum.Ten compounds had more than 50%inhibitory effect on Physalospora piricola.Among them,the fungicidal activity of the compounds III-5a,III-5g and III-5k against Physalospora piricola reached 85%,85%and 81%.（3）A study on structure-activity relationship found that the introduction of amide structure helped improve the inhibitory activity of such compounds against Sclerotinia sclerotiorum and Physalospora piricola.The introduction of amino acid fragment increased the fungicidal activity of most compounds against Physalospora piricola.Part Ⅲ:The design,synthesis and fungicidal activity of pityriacitrin alkaloids and their derivatives.（1）Synthesis of pityriacitrin alkaloid derivatives:based on the synthesis of pityriacitrin alkaloids,pityriacitrin alkaloid derivatives containing acylhydrazone structure were designed and synthesized by introducing acylhydrazone structure to C-1 ofβ-carboline with the core structure of pityriacitrin alkaloid,through an active substructure splicing strategy.（2）The results of fungicidal activity showed that all compounds were tested for fungicidal activity and most of the compounds tested showed broad-spectrum fungicidal activity against six common plant pathogens at a concentration of 50μg/L.The compound IV-8d achieved an inhibition rate of 90%against Physalospora piricola.The inhibition rates of the compounds IV-8e and IV-8g against Cercospora arachidicola hori were up to 58%,which were higher than that of the commercial fungicide carbendazim.（3）A study on structure-activity relationship found that most compounds with electron-attracting groups on the benzene ring of acylhydrazone side chain had higher fungicidal activity against Physalospora piricola than those with electron-donating groups on the benzene ring,and the activity order of compounds with electron-attracting groups on the opposite side of benzene ring of acylhydrazone side chain was:Ⅳ-8d（F）>Ⅳ-8g（CF₃）>Ⅳ-8e（Cl）>Ⅳ-8f（Br）.