吴茱萸次碱衍生物的合成及抑菌活性

Synthesis and Antifungal Activity of Rutaecarpine Derivatives

以吴茱萸次碱为原料,通过硫代反应以54.5%-87.6%的收率合成了硫代吴茱萸次碱及其5种N-取代衍生物（Ⅱ、Ⅳa-e）,采用HRMS、FTIR、1HNMR和13CNMR对产物进行了结构表征;分析了质量浓度为10 mg/L的样品对9种植物病原菌的抑菌活性。结果表明：合成的6种化合物（Ⅱ、Ⅳa-e）对植物病原真菌几乎没有抑制作用,化合物Ⅳa、Ⅳb及Ⅳd对细菌[水稻白叶枯病菌,Xanthomonas oryzae pv.oryzae（Ishiyama）]具有较明显的抑菌活性,其中N-苄基硫代吴茱萸次碱（Ⅳb）和N-（4-甲基苄基）-硫代吴茱萸次碱（Ⅳd）的抑制率分别为81.84%和59.95%。通过细胞毒活性实验发现合成的化合物（Ⅱ、Ⅳa-e）对人体正常细胞（人肺成纤维细胞,HFL1）几乎没有毒性（IC50〉80μmol/L）。

Thiorutaecarpine（Ⅱ） and its five N-substituted derivatives（Ⅳa-e） in yields of 54.5%-87.6% were synthesized from rutaecarpine by thionation. These products were confirmed by HRMS,FTIR,1 HNMR and 13 CNMR. The antifungal activities of the six compounds（10 mg/L） against nine plant pathogens were analyzed. The results showed that the synthesized six compounds had almost no inhibitory effects on the plant pathogenic fungi. However,compounds Ⅳ a,Ⅳ b and Ⅳ d exhibited obvious antifungal activities against Xanthomonas oryzae pv.oryzae（Ishiyama）. The inhibitory rates of N-benzyl thiorutaecarpine（Ⅳ b） and N-（4-methyl benzyl） thiorutaecarpine（Ⅳ d） were 81.84% and 59.95%,respectively. In addition,the thiorutaecarpine derivatives were found to be almost non-toxic（IC50 80 μmol/L） towards human normal cells（HFL1） by cytotoxicity assay.