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

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.