.1,3,4 - Thiadiazole Derivatives And Their Metal Complexes Design And Synthesis, Characterization And Nature Of The Study

1,3,4-thiadiazole and derivatives thereof are a class of valuable heterocyclic compounds, and the N-C-S functionality is responsible for the wide spectra of biological activity. 1,3,4-Thiadiazole and derivatives thereof are also used in the design of molecules in the fields of antifungal activity and antiviral activity and SAR study and used as organic ligands in coordination chemistry. Therefore,1,3,4-thiadiazole and derivatives are the research interest of fine chemicals, medicinal chemistry and coordination chemistry and widely employed in agriculture, pharmaceuticals and industry.This thesis focuses on the investigation on the preparation and properties of 1,3, 4-thiadiazole derivatives. We describe the synthesis of 22 5-(substitutedphenoxymeth-yl)-1,3,4-thiadiazol-2-yl-l-thio-β-D-glycopyranosides,11 5-substitutedpheoxymethyl-1,3,4-thiadiazol-2-ylthi-otriphenyltins,5 5-methyl-2-carboxylmethylthio-1,3,4-thiadiazole transitional metal complexes,8 new Schiff bases compounds and 6 Schiff base alkaline metal complexes, and these compounds and complexes were subjected to IR,1H NMR,13C NMR, ESI-MS and elemental analyses, and 13 of them were subjected to X-ray single-crystal diffraction. The antihyperglycemic activity of the thioglycosides were evaluated and some selected complexes were subjected to the analyses of cyclic voltammography and fluorescence and evaluations of antifungal and anticancer activities. Some SAR discussions are also included. This work provides guidance for us to perform further investigation on the structure and properties of the 1, 3,4-thiadiazole and derivatives.1. Starting from substituted phenols,11 5-substitutedphenoxymethyl-2-mercapto-1,3,4-thiadiazoles were prepared, which were coupled with 2,3,4,6-tetra-O-acetyl-β-D-glycopyranos-yl bromides in the presence of BnEt3N+Br- as PTC to yield 5-substitutedphenoxymethyl-1.3. 4-thiadiazol-2-yl-2,3,4,6-tetra-O-acetyl-1-thio-β-D-glycopyranosides. The acetylated glycol-sides were deacetylated using catalytic amount of sodium methoxide to furnish 22 desired thioglycosides, among which the structure of compound 7A'a'was further confirmed by X-ray diffraction. The used of catalytic amount of sodium methoxide provides a convenient mild procedure for the deacetylation purpose. OGTT method was used to evaluate the antihyperglycemic activity of the 22 thioglycosides, and compound 9Ah was found to be more potent than the positive control Gliclazide, which was extensive in clinical application, and compounds 9Aa and 9Bi were comparable with Gliclazide. The research mentioned above was of important significance for us to continue the work about the design and synthesis of SGLT2.2. Starting from Ph3SnCl and 5-substitutedphenoxymethyl-2-mercapto-1,3,4-thiadiazoles, 11 5-substitutedphenoxymethyl-1,3,4-thiadiazol-2-ylthiotriphenyltins were prepared by nucleo-philic substitutions. Four single crystals (R-C6H4)OCH2(C2N2S2)SnPh3 were diffracted by X-ray and all belong to tetrahedral configuration. Results from computation on the reaction course of 5a on RB3LYP/6-31G level via theoretical calculation are consistent with the crystal structure. Selected complexes were evaluated in vitro anticancer and antifungal activities, and 3 complexes were found to display potent anticancer and antifungal activities. Compound 5-(4-bromophenoxymethyl-1,3,4-thiadiazol-2-ylthiotriphenyltin exhibits IC50s of 0.085±0.011μg/ml and 0.11±0.01μg/ml against MCF-7 and CoLo205, respectively, which are both potent than Cisplatin. These results provide us experimental data about the research on seeking and screening organotin compound with much activity in anticancer and antifungal.3. Using 5-methyl-2-mercapto-1,3,4-thiadiazole as starting material,5-methyl-2-carboxyl-methylthio-1,3,4-thiadiazoles were prepared through thioetherification and hydrolysis. Based on 5-methyl-2-carboxylmethylthio-1,3,4-thiadiazoles,5 metal complexes and 1 polyligand complex were prepared by introduction of bipyridine. Complexes including Co and Zn were found to be distorted octahedrons, in which the oxygen atoms in the carboxylic group act as monodenate and bidentate along with solvent molecules and there exist hydrogen bond interactions. Investigations on the electrochemical and fluorescent properties of the Co and Zn complexes were also carried out. The study on the fluorescent properties was helpful to discover and synthesize the new fluorescence materials.4. The reaction of 5-methyl-2-hydrazinocarbonylmethylthio-1,3,4-thiadiazole with a variety of substituted benzaldehydes produced 8 new Schiff bases and transitional metal complexes thereof,2 crystals of which were obtained and subjected to X-ray diffraction. The electrochemical properties of Cu complex Ba was selected and investigated by cyclic voltammography, and the results indicated that the stability of cupric ion was enhanced after the formation of complex.In a word, the 1,3,4-thiadiazole derivatives, including thioglycosides and their metal complexes, designed and synthesized in this thesis, along with the preparation methods, structural characterization and investigation on property, can provide valuable information for 1, 3,4-thiadiazole and metal complexes thereof.