诺蒎酮-噻唑腙类化合物的合成及其抑菌活性  

Synthesis and antibacterial activity of nopinone-based thiazolyhydrazone compounds

作　　者：张成龙 郭常酉 王芸芸 赵雨珣 蒋建新[3] 王石发[1,2] ZHANG Chenglong;GUO Changyou;WANG Yunyun;ZHAO Yuxun;JIANG Jianxin;WANG Shifa(College of Chemical Engineering,Nanjing Forestry University,Nanjing 210037,Jiangsu,China;Co-Innovation Center of Efficient Processing and Utilization of Forest Resources,Nanjing Forestry University,Nanjing 210037,Jiangsu,China;College of Material Sciences and Technology,Beijing Forestry University,Beijing 100083,China)

机构地区：[1]南京林业大学化学工程学院,江苏南京210037 [2]南京林业大学林业资源高效加工利用协同创新中心,江苏南京210037 [3]北京林业大学材料科学与技术学院,北京100083

出　　处：《精细化工》2020年第11期2313-2319,共7页Fine Chemicals

基　　金：国家自然科学基金(31470592)。

摘　　要：β-蒎烯经选择性氧化制得了诺蒎酮,诺蒎酮再经羟醛缩合、酰腙化和环化反应得到15个诺蒎酮-噻唑腙类化合物。采用1HNMR、13CNMR和HRMS对所合成化合物结构进行了表征,探索了所合成化合物对金黄色葡萄球菌、白色念珠菌和肺炎克雷伯氏菌的抑菌活性。结果表明,化合物2-{2-[6,6-二甲基-3-(4-硝基苯亚甲基)二环[3.1.1]庚-2-亚基]肼基}-4-(4-氟苯基)噻唑(Ⅲe)、4-(2-{2-[6,6-二甲基-3-(4-硝基苯亚甲基)二环[3.1.1]庚-2-亚基]肼基}噻唑-4-基)苯酚(Ⅲf)、2-{2-[3-(4-氟亚苄基)-6,6-二甲基双环[3.1.1]庚-2-亚基]肼基}-4-苯基噻唑(Ⅲg)和2-{2-[6,6-二甲基-3-(4-甲基亚苄基)二环[3.1.1]庚-2-亚基]肼基}-4-苯基噻唑(Ⅲj)对金黄色葡萄球菌抑菌效果显著,其最低抑菌质量浓度分别为3.52、0.88、7.03和3.52μg/L;化合物4-{2-[2-(3-亚苄基-6,6-二甲基二环[3.1.1]庚烷-2-亚基)肼基]噻唑-4-基}苯酚(Ⅲc)对白色念珠菌有较好的抑菌活性,最低抑菌质量浓度为28.12μg/L;所有目标化合物对肺炎克雷伯氏菌的抑菌效果并不显著。化合物Ⅲf对金黄色葡萄球菌的抑制效果与硫酸卡纳霉素的抑制效果相当,具有潜在的开发价值。Fifteen nopinone thiazolidazone derivatives were obtained from nopinone by aldol condensation,acylhydration and cyclization,therein nopinone was obtained fromb-piene by selective oxidation reaction.All the target compounds were characterized by 1HNMR,13CNMR and HRMS.The antibacterial activites of these compounds against Staphylococcus aureus,Candida albicans and Klebsiella pneumonia were investigated.The results showed that 2-{2-[6,6-dimethyl-3-(4-nitrobenzylidene)bicyclo[3.1.1]heptan-2-ylidene]hydrazinyl}-4-(4-fluorophenyl)thiazole(Ⅲe),4-(2-{2-[6,6-dimethyl-3-(4-nitrobenzylidene)bicyclo[3.1.1]heptan-2-ylidene]hydrazinyl}thiazol-4-yl)phenol(Ⅲf),2-{2-[3-(4-fluorobenzylidene)-6,6-dimethylbicyclo[3.1.1]heptan-2-ylidene]hydrazinyl}-4-phenylthiazole(Ⅲg),2-{2-[6,6-dimethyl-3-(4-methylbenzylidene)bicyclo[3.1.1]heptan-2-ylidene]hydrazinyl}-4-phenylthiazole(Ⅲj)had significant inhibitory effect on Staphylococcus aureus,and the minimum inhibitory mass concentration was 3.52,0.88,7.03 and 3.52μg/L,respectively.4-{2-[2-(3-benzylidene-6,6-dimethylbicyclo[3.1.1]heptan-2-ylidene)hydrazinyl]thiazol-4-yl}phenol(Ⅲc)had good inhibitory activity on Candida albicans with a minimum inhibitory mass concentration of 28.12μg/L.However,all the target compounds had no significant inhibitory effect on Klebsiella pneumoniae.The inhibitory effect of compound Ⅲf against Staphylococcus aureus was comparable to that of kanamycin sulfate,indicating that compound Ⅲf has potential development value.

关 键 词：Β-蒎烯 诺蒎酮 噻唑腙 抑菌活性 医药原料 

分 类 号：TQ463.4[化学工程—制药化工]