Synthesis And Antifungal Activity Studies Of 3-Substituted Sulfur-containing Chromones

Chromones are a class of compounds containing benzo six-membered oxygen-containing heterocyclic skeleton,which have various biological activities,such as anti-allergic,antibacterial,anti-virus,anti-cancer and so on.Therefore,chromones are considered to be a new class of pharmacophore with broad-spectrum antibacterial.In recent years,the research on chromone compounds,especially the research and development of antifungal drugs containing chromone skeleton as lead compounds,has been widely concerned by pharmaceutical chemists and biologists.Some compounds with basic skeleton structure reported in related literature have certain antibacterial activity against specific pathogens.Therefore,a series of chromone derivatives with antibacterial activity can be obtained by chemical modification of Israel skeleton as the synthetic template of antimicrobials.In this paper,through the optimized synthesis method,a series of3-substituted sulfur-containing chromone derivatives were synthesized by modifying chromone at 3 position and their antifungal activity was determined.No strong oxidant is added in the experiment,and the method is simple and pollution-free.The main research contents are as follows:1.Synthesis of 3-substituted sulfur-containing chromone derivatives: Firstly,the suitable reaction conditions for the synthesis of 3-substituted sulfur-containing modified chromones were studied using ortho-hydroxyacetophenone as raw material.Through the exploration of reaction conditions,the template reaction conditions were established:Using 0.2 mmol of ortho-hydroxyacetophenone as raw material and 1.0 equivalent of diisopropylamine as activator,the target product 3-substituted sulfur-containing modified chromone compound was obtained in the mixed system of dimethyl sulfoxide(DMSO)of 0.2 m L and acetic acid(HOAc)of 1.0 m L at 140℃ for 20 h.According to the template reaction conditions,different ortho-hydroxyacetophenone substrates were replaced to expand the substrate,and 18 of 3-substituted sulfur-containing chromone derivatives were synthesized.The structures and purities of all target products were verified by nuclear magnetic resonance analysis to meet the test sample standards for antibacterial activity determination.2.Determination of Antibacterial activity of 3-substituted sulfur-containing chromone derivatives: The growth rate method was used to determine the antifungal activity of four common pathogenic fungi Fusarium oxysporum f.sp.cucumerinum,Phytophthora nicotianae,Fusarium graminearum and Colletotrichum capsici in plants,using the growth rate method and actinomycetone as positive control.The results of bacteriostatic activity test showed that the positive control actinomycetone had obvious bacteriostatic effect on four kinds of pathogenic fungi,while the blank control group had no inhibitory effect on four kinds of pathogenic fungi.When the sample concentration was 50 μg/m L,the 18 tested compounds had certain inhibitory effect on four kinds of pathogenic fungi,but the antibacterial effect was far less than that of the positive control cycloheximide.The antibacterial effect of all tested compounds on C.capsici was better than that of the other three pathogenic fungi.The inhibitory rates of compounds containing electron absorbing group on C.capsici and F.oxysporum f.sp.cucumerinum were better than the other two pathogenic fungi.The bacteriostatic effects of compounds with different substituents on a single pathogenic fungus were not significantly different,and the inhibitory effects of different substituents of the same compound on fungi are also different.