Synthesis, Characterization And Biological Activity Of 1,2,3-thiadiazole Derivatives

1,2,3-Thiadiazoles have attracted more and more attention due to their wide spectrum of biological activities. Especially, successfully commercialization of some 1,2,3-thiadiazoles such as tiadinil (TDL) and acibenzolar-S-methyl (BTH) as elicitors accelerated the studies on their synthesis and systemic acquired resistance (SAR).In this thesis, five types of structures including altogether 128 (117 new compounds) 1,2,3-thiadiazole derivatives were designed and synthesized according to the principles of electronic isosteric, combination of bioactive sub-structure and combinatorial chemistry. All structures synthesized were characterized by IR, 1H NMR or 13C NMR, HRMS spectra or elemental analysis. Four typical crystals of each kind of the title compounds were chosen for culturation and determination of X-ray crystal diffraction for structural confirmation. The biological activities of the title compounds were also systematically determined. The contents and results of the studies are summarized as bellows:In 1st part, 23 (12 new compounds) 4-methyl-1,2,3-thiadiazole-5- carboxylic acid aryl esters were designed and synthesized by using 4-methyl-1,2,3-thiadiazole-5- carbonyl chloride as an intermediate. The preliminary bioassay results indicated that the title compounds containing quinoline groups possessed a broad spectrum of fungicide activity with EC50 value ranged from 2.99 to 28.35μg/mL; some compounds exhibid good systemic acquired resistance for tobacco against tobacco mosaic virus (TMV) too. The results established basis for development of novel 1,2,3-thiadiazole lead with both fungicide activity and systemic acquired resistance.In 2nd part, twenty-three new N-(4-methyl-1,2,3-thiadiazol-5-yl)-N′- heterocyclic ureas were designed and synthesized by using 4-methyl-1,2,3-thiadiazole- 5-carbonyl chloride as an intermediate. Bioassay results indicated that only compoundⅡ-18 had moderate post-emergence herbicidal activity; most of the title compounds only presented good fungicide activity against Sclerotinia sclerotiorum at 50μg/mL.In the 3rd part, thirty-three novel N-[5-(4-methyl-1,2,3-thiadiazol-5-yl)-1,3,4- thiadiazol-2-yl] substituted amides were designed and synthesized according to the principle of combination of bioactive substructure using ethyl 4-methyl-1,2,3- thiadiazole-5-carboxylate as an intermediate. Bioassay results indicated that some title compounds had good fungicide activity at 50μg/mLand excellent insecticidal activity against Plutella xylostella L. at 400μg/mLand excellent larvicidal activity against Culex pipiens pallens at 5μg/mL.In 4th part, two series including altogether thirty-eight novel 3,5-dichloro-4-(1,1, 2,2-tetrafluoroethoxy) phenyl containing 4-methyl-1,2,3-thiadiazoles were designed and synthesized via Ugi reaction by 4-methyl-1,2,3-thiadiazole-5-carboxylic acid as an intermediate. Bioassay results indicated that some title compounds had good fungicide activity and insecticidal activity, most of the compounds presented a certain degree of direct inhibition activity, good inactivation and curative activity against TMV at 500μg/mLand 100μg/mL, fluorine improved the activity of the title compounds.The results of these studies indicated that 1,2,3-thiadiazole compounds exhibited various biological activities, and development of novel 1,2,3-thiadiazole lead with both fungicide and systemic acquired resistance had basis in theoretics and practice.