Study On Synthesis And Bioactivities Of 2-glucosamine Derivatives

D-glucosamine,as a kind of natural amino sugars,has extensive sources,safety,non-toxicity and various characters of physiological activities.Due to the hydroxyl and amino groups in the molecular,its can be chemically modified to obtain different derivatives.Click chemistry has the good advantages of high yield and selectivity.Triazole and its derivatives are an important nitrogen compounds.In recent years,1,4,5-substituted 1,2,3-triazole derivatives have been reported with anti-biological drugs of antiviral,antibacterial,and anti-tumor activitties.Since glucosamine has good biocompatibility,and 1,2,3-triazole derivatives also have antibacterial,anticancer and anti-HIV activities,In our paper 2-amino-D-glucose and propargyl derivatives were prepared for a series of 1,2,3-triazole derivatives.Their biological activities were tested.The main contents and conclusions of this paper were as followed:(1)The reaction conditions of click reaction such as temperature,microwave heating,reaction time and solvents were optimized.When using the DMF as solvent,the yield significantly higher than using tert-butyl alcohol(TBA)and water as solvent,using compound 2-10e as a case study for yield increased from 42.3%to 70%;When using a microwave synthesizer to carry out the reaction,not only equivalent ratio of reactants are smaller than when not using the microwave synthesizer,from 1:1.5 down to 1:1.1;The reaction time was shortened to 0.5 h under microwave heating while it was 6 h under oil-heating.Eight unreported compounds were prepared.The yields of these compounds obtained in a range from 54%to 91%.The structures of these compounds were characterized and confirmed with 1H NMR,13C NMR,IR and HRMS;The structures of eight target compounds are as followed:(2)Fluorescence spectroscopy and ultraviolet spectroscopy were used to study the interactions of bonding some target compounds with human serum albumin(HSA)and bovine serum albumin(BSA),and the force types binding sites and other information.Results showed that target compounds played a quenching role of static quenching mode on endogenous fluorescence of HSA and BSA.And with the binding of target compounds,the flurescence spectra of HSA and BSA appeared small blue shifts with the increasing concentration of target compounds,indicating the changes of micro-environment of the HSA and BSA proteins.By comparison quenching constant(Ksv),the binding constant(Ka)and Ksv,Ka changes with temperature determination of 2-glucosamine derivatives to HSA,BSA fluorescence quenching mechanism is static quenching.In addition to the binding constant of HSA with 2-(1',2',3'-triazole-4'-hydroxymethyl)-1,3,4,6-O-acetyl-D-glucose was greater than BSA,and the binding constant of other compounds with HSA binding interaction is smaller than those with BSA.(3)Isothermal microcalorimetry method online in situ was applied to study the heat production curves of E.coli(DH5a)at different concentrations of 2-amino-D-glucose derivatives at 28 ?,to explore the effect of 2-amino-D-glucose derivatives to the metabolism of DH5a.The results of experiments illustrated in a certain range of concentrations the target compounds could promote the growth of DH5a.With increasing concentration of the target compound,DH5a maximum heat power decreased.These phenomena inhinted our compounds could inhibit the growth of DH5a.These results were due to target compounds'poor water-soluability.Only at the low concentration.Poor water-solubilities of our compounds limited their range of concentrations.The next stage our goal is to increase the target compounds water-solublities via further modification and further study in vivo.