Semisynthesis and biological evaluation of some novel Mannich base derivatives derived from a natural lignan obovatol as potential antifungal agents
Semisynthesis and biological evaluation of some novel Mannich base derivatives derived from a natural lignan obovatol as potential antifungal agents
复制标题
天然木脂素 obovatol 衍生的一些新型曼尼希碱衍生物作为潜在抗真菌剂的半合成和生物学评价
DOI：
10.1016/j.bioorg.2019.103469
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发表时间：
2019
影响因子：
5.1
通讯作者：
Hui Cao
中科院分区：
文献类型：
--
作者：
Chun Yang;Ting Li;Lingyun Jiang;Xiaoyan Zhi;Hui Cao
Obovatol是从厚朴（Magnolia obovataThunb.）为了发现具有新型结构骨架的天然产物类杀菌剂，通过对obovatol进行C-4-氨甲基化修饰，合成了一系列Mannich碱衍生物，并采用孢子萌发法和菌丝生长速率法对所合成的化合物进行了体外抗植物病原真菌活性评价。通过1H NMR、13 C NMR和HR-MS对化合物2k进行了结构表征，并通过单晶X射线衍射对化合物2k进行了结构分析。在所有衍生物中，化合物2b（IC 50 = 28.68 μg/mL）和2g（IC 50 = 16.90 μg/mL）表现出比两个阳性对照（恶霉唑和苯醚甲环唑）更大的对灰葡萄孢孢子萌发的抑制。化合物2c、2f和2g对B.浓度为100 µg/mL时，平均抑制率（AIR）>90%。此外，构效关系（SAR）表明，在Obovatol的C-4位上引入二乙基氨基、吡咯基、1-甲基-哌嗪基或1-乙基-哌嗪基基团可能比引入4-苯基-哌嗪基或4-苯基-哌啶基基团更有可能产生潜在的抗真菌化合物。
Obovatol, a novel lignan isolated from the leaf and stem bark ofMagnolia obovataThunb exhibits many important biological activities. To discover natural-product-based potential fungicides with novel structural skeletons, a series of Mannich base derivatives were prepared by the C-4-aminomethylated modification of obovatol and all synthesized compounds were evaluated for antifungal activitiesin vitroagainst several phytopathogenic fungi using the spore germination method and the mycelium growth rate method. Furthermore, their structures were also characterized by1H NMR,13C NMR, and HR-MS, and compound2kwas further analyzed by single-crystal X-ray diffraction. Among all of the derivatives, compounds2b(IC50= 28.68 µg/mL) and2g(IC50= 16.90 µg/mL) demonstrated greater inhibition ofBotrytis cinereaspore germination than two positive controls, hymexazol and difenoconazole. Compounds2c,2f, and2gdisplayed potent mycelial growth inhibition ofB. cinereawith an average inhibition rate (AIR) of >90% at a concentration of 100 µg/mL. Additionally, the structure-activity relationships (SARs) suggested that the introduction of a diethylamino, pyrrolyl, 1-methyl-piperazinyl or 1-ethyl-piperazinyl groups on the C-4 position of obovatol may be more likely to yield potential antifungal compounds than the introduction of 4-phenyl-piperazinyl or 4-phenyl-piperidinyl groups.