Synthesis And Fungicidal Activity Of Tetramic Acid Derivatives Containing Disubstituted Hydrazine Moiety

Tetramic acid derivatives were found exhibiting antitumor,antiviral,antibacterial,antifungal and herbicidal activities.Many tetramic acid derivatives containing substituted phenylhydrazine groups at the 3-position were designed and synthesized.Some of the compounds showed excellent antifungal activity.In this paper,a series of pyrrolidine-2,4-dione derivatives containing disubstituted hydrazine moiety and another series of pyrrolidine-2-one derivatives containing two moieties of disubstituted hydrazine and carbonic ester were synthesized.The antifungal activities of the compounds were also evaluated.Sixty pyrrolidine-2,4-dione derivatives containing disubstituted hydrazine moiety A-H were prepared by the reaction of phenylhydrazine containing methyl,ethyl,butyl,allyl,benzyl or methoxycarbonyl in the position of a-N with substituted pyrrolidine-2,4-dione.Twenty four pyrrolidine-2,4-dione derivatives containing disubstituted hydrazine moiety and carbonic ester moiety were prepared by the reaction of esterification from chloroformates and pyrrolidine-2,4-dione derivatives containing substituted phenylhydrazine moiety.The structures of the compounds were confirmed by FT-IR,1H NMR,MS and elemental analysis.The structure of the compound I4 was also analyzed by X-ray diffraction.The antifungal activities of the title compounds against Fusarium graminearum,Botrytis cinerea,Rhizoctonia cerealis,Rhizoctonia solani and Colletotrichum capsici were screened in vitro with mycelia growth rate method.The EC50 values were evaluated using the double broth dilution method.The compounds A-H displayed notable fungicidal activities against R.cerealis.The componds B8 and C8 displayed good activity with EC50 values of 1.626 p,g/mL and 2.043 ?g/mL,respectively.The compounds I-K displayed excellent activity.The compound J10 exhibited the best activity against F.graminearum,it's EC50 value was 0.2162 ?g/mL,lower than the value 0.4947 ?gg/mL of the control drug carbendazim.The compound K4 had the lowest EC50 value against B.cinerea,it's 0.1097?g/mL,lower than the value 0.3577 ?g/mL of the control drug procymidone.The compound K2 gave the best activity against R.solani,it's EC50 value 0.0704 ?g/mL was lower than the value 0.5417 ?g/mL of carbendazim.The compound K3 showed the best activity against C.capsici,it's EC50 value 0.1637 ?g/mL was lower than the value 0.3325?g/mL of azoxystrobin.The structure and activity relationship of the compounds A-H was analyzed.It was found that a smaller group in N-1 of phenylhydrazine favored the activity such as the compounds containing methyl.The compounds with the group of Cl or Br at 4-position of phenyl ring showed best activity.For the compounds I-K,which containing isopropyl ester and the group of Cl or Br at 4-position of phenyl ring showed excellent activity.The 3D-QSAR model of CoMFA was established to analyze the structure and activity relationship of some compounds of A-H against R.cerealis.It concluded that a smaller group in N-1 of phenylhydrazine and a bulky negative charge group at 4-position of phenyl ring favored the activity.