Synthesis And Biological Activity Of Novel Compounds Containing 4-hydroxypyrolin-2-one And 1,3,4-oxadiazole Sulfide (sulfone)

1,3,4-oxadiazole structure compounds have extensive biological activities, such as antibacterial, antifungal, anti-inflammatory, anti anxiety and anti tuberculosis. Amide compounds is one of the hot spots in the study of new pesticides in recent years because which have antimicrobial, insecticidal, weeding and antiviral activity. 4-hydroxy pyrroline-2-ketone compounds is a kind of natural product analogues and have a wide range of pesticide and pharmaceutical and biological activities such as bactericidal, insecticidal, herbicidal, antitumor, antiviral and so on. This paper introduce the amide bond and 4-hydroxy pyrrole-2-ketone into 1,3,4-oxadiazole structure, respectively, to obtained a series 1,3,4-oxadiazole thioacetamide compounds and containing 4-hydroxy pyrroline-2-ketone of 1,3,4-oxadiazole.The starting material substituted benzoic or benzyl acid was treated with four steps including esterification, hydrazidation, cyclization, and acidification to give one of the most important intermediate 5-substituted-1,3,4-oxadiazole-2-thiol. Substituted aniline reaction with 2-bromoacetyl bromide and get the 2-bromine-N-?4-substituted phenyl? ethyl amide. The important intermediate 5-substituted-1,3,4-oxadiazole-2-thiol reaction with 2-bromine-N-?4-substituted phenyl? ethyl amide obtained 30 target compounds of class A. Then important intermediate 5-substituted-1,3,4-oxadiazole-2-thiol reacted with chloroacetic acid obtained 5-substituted-1,3,4-oxadiazole-2-thiol acetic acid. Further in the presence of condensation agent DCC reaction with substituted glycine ethyl ester cyclization to obtain the target compounds of class B. Now have been synthesized 20 target compounds of class B and all of the compounds were confirmed by ¹H NMR, ¹³C NMR, MS, IR.The anti-TMV activity were tested by the half-lesf method in vivo of all the target compounds. The result showed that most of the target compounds show acceptable curative activity and protection activity. Among them, compounds A-8, A-10, A-12, A-23, and A-27 exhibited good curative activity against TMV with the inhibition ratio of 59.8%, 57.5%, 57.5%, 60.2%, 57.3%, 57.4%, respectively, which are comparable to that of Ningnanmycin. The compounds A-8, A-10, A-12, A-15, A-23, A-27, A-29 for curative activity against TMV with the EC50 value of 239.5, 284.5, 293.6, 284.3, 236.2, 278.0, 274.9, 275.3 ?g/m L, respectively, showed comparable activity as that of Ningnanmycin?EC50 value was 273.2 ?g/m L?, It is noted that all the title compounds exhibited applicable protection activity but lower than that of Ningnanmycin.Turbidimeter test was employed to examine their antibacterial activities in vitro, all the target compounds exhibited certain inhibition effects against the three bacteria at the concentration of 200 ?g/m L and 100 ?g/m L. Among them, compound A-16 and A-29 exhibited good bioactivity against Xoo with the inhibition ratio of 96.2% and 95.9% at the concentration of 200 ?g/m L, respectively. Compounds A-1, A-20, A-24, A-29 showed good inhibition effect against Xac up to 70% higher than the control agent Thiodiazole copper. Compounds B-1, B-2, B-3, B-11, B-15 and B-16 showed good inhibition effect against Xoo up to 90% at the concentration of 200 ?g/m L. The inhibitory activity of copounds B-2, B-9, B-11 and B-15 also can up to 90% at the concentration of 100 ?g/m L which higher than the control agent Bismerthiazol. The inhibition activity of copounds B-1, B-2, B-3, B-11 and B-15 against Xoo with the EC50 value of 40.23, 8.61, 17.59, 7.30 and 39.59 ?g/m L better than the control agent Bismerthiazol?EC50 value was 92.61 ?g/m L?. At the concentration of 200 ?g/m L copounds B-1, B-2, B-3, B-11, B-15 and B-16, the inhibitory activity of Xac can up to 70% higher than the control agent Thiodiazole Copper Compounds B-2, B-11, B-15 can also up to 50% at the concentration of 200 ?g/mL.