含哌嗪环的叔丁基三唑醇类化合物的合成及体外抗真菌活性

目的:设计合成含哌嗪环侧链的叔丁基三唑醇类化合物;并研究其体外抗真菌活性.方法:以一氯频哪酮为起始原料经多步反应合成含哌嗪环的叔丁基三唑醇类化合物,化合物结构经1HNMR确证为1-(1H-1,2,4-三唑-1-基)-2-叔丁基-3-(4-取代哌嗪)-1-基]-2-丙醇类化合物;选择白念珠菌(Candida albicans)ATCC76615、新生隐球菌(Cryptococcus neoformans)ATCC32609、热带念珠菌(Candida tropicalis)、近平滑念珠菌(Candida parapsilosis)、红色毛癣菌(Trichophyton rubrum)、羊毛样小孢子菌(Microsporum lauosum)、紧密着色真菌(Fonsecaea compacta)以及薰烟曲霉菌(Aspergillus fumigatus)8种真菌为实验菌株,按国际标准抗真菌敏感性实验方法测定体外抑菌活性.结果:设计合成了11个新化合物.所有目标化合物对8种真菌均具有一定的抑制作用.结论:化合物9对新生隐球菌的活性高于对照药氟康唑和伊曲康唑,化合物8对薰烟曲霉菌的活性高于对照药氟康唑,这两个化合物有进一步研究的价值.

Synthesis and antifungai activity of triazole derivatives with side chain containing tert-butyi and 4-substituedpiperazin-l-yi

Objective:To design and synthesize the triazole derivatives with the side chain containing tert-butyl and 4-substitued-piperazin-1-yl and to investigate their antifungal activities in vitro. Methods: The triazole derivatives were synthesized through several steps using 3, 3-dimethylbutyryl chloride as the starting material. All the target compounds were confirmed by 1HNMR to be 1-(1H-1, 2, 4-triazol-1-yl)-2-(3, 3-dimethyl)-3-(4-substituted)-piperazin-1-yl-2-propanols. Candida albicans (ATCC76615), Cryptococcus neoformans (ATCC32609), Candida tropicalis, Candida parapsilosis, Trichophyton rubrum, Microsporum lauosum, Fonsecaea compacta, and Aspergillus fumigatus were used to test the anti-fungal activities of the target compounds in vitro according to the National Committee for Clinical Laboratory Standards (NCCLS). Results: Eleven target compounds were obtained and all of them were firstly reported. We also found that all the 11 compounds had certain antifungal activities against the 8 tested strains. Conclusion: Compound 9 has a better effect against Cryptococcus neoformans than fluconazole and itraconazole; compound 8 has a better effect against Aspergillus fumigatus than fluconazole; these two compounds deserve further study.