Design And Synthesis Of Novel 1,2,3-triazoles And Their Antibacterial And Antifungal Activity

1,2,3-Triazole compounds as an important type of nitrogen-containing aromatic heterocyclic compounds exhibited wide biological activities and have attracted extensive attention. Promoted by the recent progress of 1,2,3-triazoles in medicinal chemistry, a series of novel D-glucose- and bisphenol A-derived 1,2,3-triazoles bearing various substituted benzenes were designed and synthesized in this thesis. All these newly synthesized compounds were evaluated for their antibacterial and antifungal activities in vitro.Prelimary structure-activity relationship was also discussed.Bisphenol A-derived 1,2,3-triazole compounds 35 and 37 were synthesized in excellent yields via 1,3-dipolar cycloaddition starting from bisphenol A and propargyl bromide as materials.Glucose-derived 1,2,3-triazoles 40,43 and 46 were synthesized by the 1,3-dipolar cycloaddition of O-propargyl a-D-glucoside with a series of corresponding azides starting from commercially available methyl a-D-glucoside. The protected glucose 1,2,3-triazoles were easily deprotected with 5% hydrochloric acid to afford compounds 41,44 and 47.Subsequently, the salts were neutralized with 25% analytic grade ammonium hydroxide to give compounds 42,45 and 48.All the new compounds were characterized by UV-vis, IR,1H NMR,13C NMR and MS spectra. The DEPT, APT,'H-'H and'H-13C 2D NMR spectra for some compounds were also recorded.The antifungal and antibacterial assay in vitro indicated that all the synthesized 1,2,3-triazoles exhibited different degree of inhibitory activity. Glucose-derived 1,2,3-triazoles gave better antifungal and antibacterial activities than bis-phenol A derived bis-triazoles. Generally, the deprotected glucose aryl 1,2,3-triazoles showed better inhibitory than alkyl triazoles. The hydrochlorides 36c and 42d with 3-chlorobenzyl moiety and 3,4-dichlorophenyl group respectively exhibited good inhibitory against C.albicans and E. coli, which were superior to the reference drugs Fluconazole and Chloramphenicol respectively. Notably, compound 45a bearing (CH2)7CH3 group exhibited good and broad inhibitory activity with the MIC values ranging from 0.055 to 0.44 mM. Besides, glucose derived aryl triazoles 48f-h and 48k bearing 2,4-dichlorophenyl,3-fluoro-4-chlorophenyl, trifluoromethyl, as well as ethoxycarbonylphenyl moiety respectively and their corresponding hydrochlorides showed the most potent antimicrobial activity, even comparable or superior to the clinical drugs (Fluconazole and Chloramphenicol) among all the glucose derived various phenyl triazoles. Bisphenol A derived 1,2,3-triazoles 35b bearing 2,4-difluoro moiety as well as alkyl triazoles 37b and 37c gave broad antimicrobial activity against the tested bacterial and fungal strains with MIC values ranging from 0.09 to 0.44 mM. These results showed that the present series containing 1,2,3-triazole is necessary to further investigate for new antimicrobial agents with potent activity and minimal toxicity.The preliminary structure-activity relationship revealed that glucose-derived 1,2,3-triazoles with good biological compatibility and water solubility, gave better antimicrobial activity than bisphenol A derived 1,2,3-triazoles. Besides, the type of substitutents, the number and location of the halogen atom in the aryl ring had noticeable effect on the antibacterial and antifungal activities.1,2,3-Triazoles with some electron-withdrawing substituents in bezene ring or (CH2)7CH3 moiety gave better activities than short ones.In the thesis, ninety three compounds were successfully synthesized. Among the synthesized compounds, seventy seven compounds were new including eleven bis-phenol A derived 1,2,3-triazoles, twenty-two protected glucose derived 1,2,3-triazoles, twenty-two deprotected glucose derived 1,2,3-triazoles and twenty-two glucose derived 1,2,3-triazole hydrochlorides.