吴茱萸次碱衍生物的合成及抑菌活性

Synthesis and Antifungal Activity of RutaecarpineDerivatives

摘要:

以吴茱萸次碱为原料，通过硫代反应等以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10 μg/mL的样品对9种植物病原菌的抑菌活性。结果表明：合成的六种化合物（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 > 80 μmol/L）。

Abstract:

In order to study and develop the indole quinazoline alkaloid of the traditional Chinese medicine evodia, the thiorutaecarpine and five N-substituted derivatives were synthesized from rutaecarpine by thionation. The structures of the products were confirmed by HPLC-HRMS, IR, 1HNMR and 13CNMR. The antifungal activity on nine plant pathogens of the compounds (Ⅱ and Ⅳa~e, 10μg/mL) was analyzed, and it was found that there was almost no inhibitory effect on the plant pathogenic fungi, and N-substituted thiorutaecarpine (Ⅳa, Ⅳb and Ⅳd) had obvious antifungal activity against bacteria [Xanthomonas oryzae pv.oryzae (Ishiyama)]. The inhibitory rates of N-benzyl sulfo-rutaecarpine (Ⅳb) and N-(4-methyl benzyl) sulfo-rutaecarpine (Ⅳd) were 81.84% and 59.95%, respectively. The rutaecarpine derivatives were found to be almost non-toxic (IC50 > 80 μmol/L) to human normal cells (HFL1) by cytotoxicity assay.