Synthesis And Fungicidal Activity Of Phenazine-1-Carboxamide Compounds

Shensinmycin belongs to the class of phenazines,and its chemical name is Phenazine-l-carboylic acid(PCA).It is a very important natural product widely distributed in Streptomyces and Pseudomonas aeruginosa.It has good preventive and therapeutic effects on various fungal diseases such as Fusarium oxysporum sp.cumcumerinum,Fusarium oxysporum sp.niveum and Rhizoctonia solani.Due to its broad-spectrum fungicidal effects,low toxicity and eco-friendly characteristics,the compoundhas been registered and widely used as a new microbial agricultural fungicide in China.Based on the previous results in the laboratory,PCA was used as the lead compound to design and synthesize a series of novel structures of phenazine-1-carboxamides containing 1,3,4 thiadiazole and 1,3,4-oxadiazole moieties(Figure 1).They were 14 N-(5-substituted phenyl-1,3,4-thiadiazol-2-yl)phenazine-1-carboxamides and 14 N-(5-substituted phenyl-1,3,4-oxadiazol-2-yl)phenazine-1-carboxamides respectively.The key intermediates 2-amino-5-aryl-1,3,4-thiadiazole and 2-amino-5-aryl-1,3,4-oxadiazole were obtained by a series of reactions,and then reacted with phenazine-1-carbonyl chloride to getthe title compounds II-1～II-28).The reaction is simple and the yields wereabove 80% generally.The title compounds werecharacterized by mass spectrometry,elemental analysis,and nuclear magnetic resonance spectroscopy.In vitro and in vivo fungicidal activities of title compounds were tested.The results showed that compounds II-1～II-28 had obvious fungicidal activity against Fusarium graminearum,which was better than that of PCA.The inhibitory activity of all compounds against Botrytis cinerea was far lower than the positive control simazine.Compound II-8 and II-22 showed better activity relative to other compounds.The satisfactory result was that both antibacterial activity of compound II-22 against Pyrosporia oryzae and Phytophthora capsici and the antibacterial activity of compound II-8 against Rhizoctonia solani were nearly equivalent to Shensinmycin.Compound II-22 showed good fungicidal effects on Pyrosporia oryzae and Phytophthora capsica.In addition,the inhibitory rate of all compounds against Fusarium graminearum was higher than that of Shenzaimycin and the activity of compound II-8(58.69%)and II-22(55.37%)against F.graminearum was twice that of Shensinmycin (25.14%).