Synthesis And Fungicidal Activity Evaluation Of 2-thiazolyl Amide Cyclohexane-sulfonamide

Sulfonamides have excellent biological activity.Initially,it was widely used in medicine.Later,people gradually discovered the potential of sulfonamide compounds as agricultural bactericides,which gradually attracted attention and became a hot spot for the development of new bactericides.A large number of sulfonamide compounds with bactericidal activity have been reported.In addition,compounds containing a heterocyclic ring structure have long been attracting attention due to their extensive biological activity,and introduction of a heterocyclic ring into a lead compound has always had unexpected effects.Thiazole compounds with excellent biological activity are one of the research hotspots in recent years.Based on the previous research work in the laboratory,this article continues to use cyclohexane sulfonamide as the lead compound for further optimization research.Firstly,12novel 2-thiazolylamidocyclohexane sulfonamides were prepared by reacting 12 different2-arylthiazolecarboxylicacidswiththereductiveaminationproductsof cyclohexamethyldithiocarbamate?YYG-1^YYG-12?Then,through the bactericidal activity assay,the thiazole group that contributes most to the activity of the compound is selected and used as an active group?active group 1?.It was docked with 10 newly synthesized2-aminocyclohexane sulfonamides(III₁ to III₁₀),and another batch of 10 novel2-thiazolylamidocyclohexane sulfonamide compounds was synthesized?YYG-13^YYG-22?.In addition,in order to further explore the application value and application prospects of thiazolecarboxamide-reactive groups in the derivation of cycloalkylsulfonamide compounds,we docked the other excellent thiazole active group?reactive group 2?from the same commercially available thiazole fungicide with the same 10 2-aminocyclohexylsulfonamide?III1 to III10?and 374,obtained 11 novel 2-thiazolylaminocyclohexane sulfonamide compounds?YYG-23^YYG-33?.The structure of target 2-thiazolylaminocyclohexane sulfonamide?YYG-1^YYG-33?was confirmed by ¹H NMR,¹³C NMR,MR and elemental analysis.Using Botrytis cinerea as the main target,we used the mycelial growth rate method,the spore germination method,and the tomato live potting method to comprehensively evaluate the antibacterial activity of the target compounds.Pyricularia grisea,Rhizoctonia solani Kühn,and Phytophthora capsici were used to study the bactericidal spectrum of the compounds.In addition,we also conducted a preliminary study on the structure-activity relationship of the target compounds based on the results of biological activity measurements.By studying the antibacterial activity of compounds YYG-1^YYG-12,we found that the inhibitory rate of this series of compounds on mycelial growth was low,but the inhibitory rates of compounds YYG-2,YYG-5 and YYG-10,in spore germination and in vivo,were higher than 70%,showing a good antibacterial activity.At the same time,a preliminary study found that this series of compounds?such as YYG-10?also has outstanding antibacterial activity against the other three pathogenic bacteria,and sterilizing puerarin is relatively broad.The structure-activity relationship study found that when the substituent R¹ is located in the meta or para position of the benzene ring and is an electron-withdrawing group,the activity is relatively high.Among them,when the para substituent on the phenyl ring is a strong electron-withdrawing group?such as YYG-10?,the activity is relatively good,and the antibacterial activity is broader.Therefore,we want to change the structure of the sulfonamide moiety?R²?while keeping the structure?R¹=4-CF₃?on the thiazole ring of the compound YYG-10 unchanged,and study the effect of different substituent R² on the structure-activity relationship of 2-thiazolamidocyclohexane sulfonamide.By studying the antibacterial activity of compounds YYG-13^YYG-22,we found that compounds YYG-16,YYG-21 and YYG-22 have better antibacterial activity.In tomato pot experiments,the control effects of YYG-21 and YYG-22 were 95.69%and 98.61%,respectively,which were higher than those of the control drugs boscalid?81.99%?and procymidone?44.17%?.Preliminary studies have shown that this series of compounds also has good inhibitory activity against rice blast fungus.The structure-activity relationship study found that when the substituent R² is a chlorine atom or a bromine atom,the activity of the compound against Botrytis cinerea is higher than that when R² is a fluorine atom;when the substituent is in the amino position,the inhibitory activity against Botrytis cinerea is relatively high.By studying the antibacterial activity of compounds YYG-23 to YYG-33 we found that this series of compounds exhibited a good antibacterial activity.In tomato pot experiments,the control effects of compounds YYG-24 and YYG-27 were 82.97%and 87.34%,respectively,which were higher than those of the control drugs boscalid?81.99%?and procymidone?44.17%?.The control efficacy of compounds YYG-30,YYG-32 and YYG-33also exceeded 70%,better than the control agent procymidone.The structure-activity relationship study found that when the substituent R² is a bromine atom or a chlorine atom and it is in the para position of the amino group,the antibacterial activity is good and the bactericidal spectrum is wide;when the trifluoromethyl exists in the ortho position of the amino group,the antibacterial activity of the compound can be enhanced.In summary,we have screened two thiazole groups with excellent activity and several compounds with high inhibitory activity against Botrytis cinerea in the activity assay of the above compounds.A preliminary study was conducted on the bactericidal spectrum of the target compound.Studies have shown that the active thiazolecarboxamide group has a high application value in the derivatization of cycloalkylsulfonamide compounds,and has a good application prospect,which lays the foundation for the design and synthesis of subsequent cycloalkylsulfonamide derivatives.