含1,3,4-噻(噁)二唑吩嗪-1-甲酰胺类衍生物的合成与杀菌活性

Design,synthesis and fungicidal activities of phenazine-1-carboxamida conjugates of 1,3,4-thia(oxa)diazole

对广泛存在于链霉菌和铜绿假单胞菌中的一种天然活性物质——申嗪霉素进行了结构修饰,合成了一系列高活性的含1,3,4-噻(噁)二唑的申嗪霉素衍生物I1~I28。杀菌活性测定结果表明:所有目标化合物对禾谷镰刀菌具有较好的杀菌活性,均明显优于母体申嗪霉素。离体杀菌活性测定结果显示,化合物I_(8)(EC_(50)=33.25μg/mL)和化合物I22(EC_(50)=46.52μg/mL)对禾谷镰刀菌的杀菌活性是申嗪霉素(EC_(50)=128.54μg/mL)的3~4倍。活体杀菌活性显示,在500μg/mL质量浓度下,化合物I_(8)(58.69%)和化合物I22(55.37%)对禾谷镰刀菌的抑制率是申嗪霉素(25.14%)的两倍。构效关系分析结果表明,在苯环上引入吸电子基团对化合物的活性不利;而引入给电子基团则有利于提高其杀菌活性。同时,同一取代基在苯环上的取代位置依据活性的高低排列顺序为:邻位>对位>间位。这些结果可用于指导该类化合物的进一步结构改造。

Phenazine-1-carboxylic acid(PCA),isolated from Pseudomonas,is a very important fungicidal agent.PCA and its derivatives revealed good biological activities in the field of medicine and agrichemicals.In this paper,two series of PCA derivatives containing 1,3,4-thiadiazole and 1,3,4-oxadiazole were designed and synthesized to explore novel fungicidal candidates.Their in vitro and in vivo fungicidal activities were evaluated.The title compounds I_(8)(X=S,R=2-OCH3)and I22(X=O,R=2-OCH3)had EC_(50) vaues of 33.25μg/mL and 46.52μg/mL against Fusarium graminearum,respectively,which were about 3-4 times better than of PCA(EC_(50)=128.54μg/mL).In vivo results showed that compounds I_(8)and I22 gave better bioactivity(inhibitory rates of 58.69%and 55.37%at 500μg/mL,respectively)against F.graminearum than that of PCA(25.14%).Preliminary structure-activity relationship study found that the introduction of electron-donating groups were favored to improving the activity of the derivatives,and the substitution at ortho-position of benzene ring would be favored to fungicidal activity.The substitution position of the same substituent on the benzene ring was in the order of o>p>m according to the bioactivity.These results can be used to guide the further structural modification of these compounds for novel fungicidal agent.