吡咯连接的1,3,4-恶二唑是一种非常重要的药效团,具有广泛的治疗作用,例如抗结核,抗癫痫药,抗艾滋病毒,抗癌,抗炎,抗氧化剂,和抗菌活性。D-核糖和L-氨基甲酯在DMSO中与草酸在2.5atm和80°C下进行一锅美拉德反应,以合理的产率迅速产生了吡咯-2-甲醛平台化学品,用于合成吡咯连接的1,3,4-恶二唑。苯甲酰肼与吡咯平台的甲酰基反应以提供相应的亚胺中间体,经历了I2介导的氧化环化反应,形成了吡咯连接的1,3,4-恶二唑骨架。评估了目标化合物的结构和活性关系(SAR),这些化合物具有不同的氨基酸烷基或芳基取代基和苯甲酰肼苯环上的吸电子或给电子取代基,对大肠杆菌的抗菌活性,金黄色葡萄球菌,和鲍曼不动杆菌作为代表性革兰氏(-)和革兰氏(+)细菌。来自氨基酸的支链烷基显示出更好的抗菌活性。具有碘苯酚取代基的5f-1对鲍曼不动杆菌的活性绝对优越(MIC<2μg/mL),一种对常用抗生素具有高抗性的细菌病原体。
Pyrrole-ligated 1,3,4-oxadiazole is a very important pharmacophore which exhibits broad therapeutic effects such as anti-tuberculosis, anti-epileptic, anti-HIV, anti-cancer, anti-inflammatory, antioxidant, and antibacterial activities. A one-pot Maillard reaction between D-Ribose and an L-amino methyl ester in DMSO with oxalic acid at 2.5 atm and 80 °C expeditiously produced pyrrole-2-carbaldehyde platform chemicals in reasonable yields, which were utilized for the synthesis of pyrrole-ligated 1,3,4-oxadiazoles. Benzohydrazide reacted with the formyl group of the pyrrole platforms to provide the corresponding imine intermediates, which underwent I2-mediated oxidative cyclization to the pyrrole-ligated 1,3,4-oxadiazole skeleton. The structure and activity relationship (SAR) of the target compounds with varying alkyl or aryl substituents of the amino acids and electron-withdrawing or electron-donating substituents on the phenyl ring of benzohydrazide were evaluated for antibacterial activity against Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii as representative Gram(-) and Gram(+) bacteria. Branched alkyl groups from the amino acid showed better antibacterial activities. Absolutely superior activities were observed for 5f-1 with an iodophenol substituent against A. baumannii (MIC < 2 μg/mL), a bacterial pathogen that displays a high resistance to commonly used antibiotics.