马 媛, 段文贵*, 林桂汕, 刘陆智, 黄正松, 雷福厚
(1.广西大学 化学化工学院, 广西 南宁 530004; 2.广西林产化学与工程重点实验室, 广西 南宁 530008)
紫苏醛基席夫碱-(硫)脲化合物的合成及生物活性
MA Yuan
马 媛1, 段文贵1*, 林桂汕1, 刘陆智1, 黄正松1, 雷福厚2
(1.广西大学 化学化工学院, 广西 南宁 530004; 2.广西林产化学与工程重点实验室, 广西 南宁 530008)
以紫苏醛为原料,设计合成了13个未见文献报道的紫苏醛基席夫碱-(硫)脲化合物(5a~5m),通过FT-IR、1H NMR、13C NMR和ESI-MS对其结构进行了分析和表征,并测试了目标化合物的抑菌和除草活性。生物活性测试表明,在质量浓度50 mg/L下,目标化合物5f(R=p-FAr)对苹果轮纹病菌的抑制率达90.0%(接近阳性对照嘧菌酯),化合物5d(R=Ar)对番茄早疫病菌的抑制率达91.8%(接近阳性对照嘧菌酯)。在质量浓度100 mg/L下,目标化合物5c(R=环己基)、5i(R=p-CH3Ar)和5a(R=CH3)对油菜胚根生长的抑制率分别为77.6%、75.3%和67.4%(高于阳性对照丙炔氟草胺)。总体上,取代苯基硫脲类目标化合物的抑菌和除草活性优于取代苯基脲类目标化合物。
紫苏醛;席夫碱-(硫)脲;合成;抑菌活性;除草活性
紫苏醛又称二氢枯茗醛(perillaldehyde,4-异丙烯基环己-1-烯-1-醛,C10H14O),是一种具有樱桃、油脂和枯茗醛香气的单萜类化合物,天然存在于紫苏、莲叶桐和香柠檬中[1],可用于调制茉莉、水仙等化妆品用花香型香精,也可用于调制柠檬、留兰香及香辛料等食品用香型香精。紫苏醛是一种天然香料,也是一种重要的有机合成中间体。然而由于其天然含量少,不能满足市场需求,因此,主要来源于以α-蒎烯为原料的人工合成,即先将α-蒎烯经烯丙位甲基氧化制备桃金娘烯醛,继而催化四元环开环异构得到紫苏醛。由于紫苏醛自身具有抗氧化、抗抑郁、抗炎、抑菌、抗癌和杀虫等多种生物活性[2-7],因此在日化、医药和农药等行业有着广泛的应用。此外,紫苏醛衍生物也表现出抑菌、杀螨、驱蚊、除草和抗衰老等多种生物活性[8-12]。脲及硫脲类化合物表现出良好的抑菌[13-14]、抗癌[15]、除草[16-17]、杀虫[18]、抗病毒[19]、抗氧化[20]、抗炎[21]和植物调节[22]等生物活性,近年来备受关注。基于以上事实和近年来课题组对松香松节油基生物活性化合物的研究成果[14,16-18,23-26],本研究设计将席夫碱、(硫)脲基团引入到紫苏醛骨架中,合成得到一系列新型的紫苏醛基席夫碱-(硫)脲化合物,初步探索了合成条件,利用FT-IR、1H NMR、13C NMR和ESI-MS等多种分析方法对目标产物进行了结构表征,并测试了目标产物的抑菌和除草活性,旨在为我国天然优势资源松节油的深度开发利用提供新途径。
1.1 原料、试剂与仪器
紫苏醛,湖南长沙凯美香精香料股份有限公司,使用前经亚硫酸氢钠法分离纯化,质量分数为95.6%;叔丁氧羰基肼和系列胺类均为市售分析纯。
Nicolet iS50 FT-IR红外光谱仪,美国Thermo Scientific公司;AVANCE Ⅲ HD 600 MHz超导核磁共振仪,瑞士Bruker公司;TSQ Quantum Access MAX液相色谱-质谱联用仪,美国Thermo Scientific公司;Agilent 6890气相色谱仪,美国Agilent Technologies公司;海能MP420全自动熔点仪,济南海能仪器股份有限公司。
1.2 合成路线
紫苏醛基席夫碱-(硫)脲系列化合物的合成路线如下所示:
1.3 中间产物的合成
1.3.1 异硫氰酸酯/异氰酸酯的合成 参考文献[27]合成系列异硫氰酸酯和异氰酸酯。
1.3.2 化合物(3)的合成 参考文献[28]合成化合物3。将叔丁氧羰基肼2 (0.66 g,5.0 mmol)溶于25 mL乙腈中,室温搅拌下通过恒压滴液漏斗逐滴加入6.0 mmol异硫氰酸酯或异氰酸酯的乙腈稀释液5 mL。硅胶薄层色谱(TLC)监测反应进程,待叔丁氧羰基肼反应完全后停止反应,旋转蒸发除去溶剂。以石油醚/乙酸乙酯(体积比1 ∶1)为洗脱剂,柱层析提纯,得到白色固体3。
1.3.3 系列氨基硫脲和氨基脲类化合物(4)的合成 参考文献[29]合成化合物4。将5 mmol化合物3溶于10 mL二氯甲烷中,室温搅拌下,逐滴加入1 mL三氟乙酸(TFA)。硅胶薄层色谱(TLC)监测反应进程,待原料反应完全后停止反应,旋蒸除去溶剂。向剩余物质中加入适量乙酸乙酯,用饱和碳酸氢钠溶液洗涤至pH值为7~8。旋转蒸发除去乙酸乙酯,以石油醚/乙酸乙酯(体积比3 ∶1)为洗脱剂,柱层析提纯,得到白色固体4a~4m。
1.4 目标化合物(5a~5m)的合成
将3.0 mmol化合物4溶于10 mL无水乙醇,加入装有回流冷凝装置的两口瓶中,搅拌、加热至回流。将3.6 mmol紫苏醛1溶解于5 mL无水乙醇中,通过恒压滴液漏斗滴加至反应体系中。用TLC监测反应进程,待反应完全后,旋转蒸发除去溶剂。以石油醚/乙酸乙酯(体积比20 ∶1)为洗脱剂,柱层析提纯,得到目标产物5a~5m。
1.5 目标化合物的结构表征
采用KBr压片法测定目标化合物的FT-IR;以CDCl3为溶剂,在600 MHz 核磁共振仪上进行1H NMR和13C NMR分析;采用电喷雾电离源(ESI)在液相色谱-质谱联用仪(LC-MS)上进行质谱分析。
1.6 目标化合物的生物活性测试
采用离体法(也称琼脂稀释法)测试目标化合物的抑菌活性[23];采用油菜平皿法和稗草小杯法测试目标化合物的除草活性[24]。
2.1 目标产物5a~5m的表征
2.2 生物活性测试结果
2.2.1 抑菌活性 由表1可知,在质量浓度50 mg/L下,目标化合物5a~5m对黄瓜枯萎病菌、花生褐斑病菌、苹果轮纹病菌、番茄早疫病菌和小麦赤霉病菌均具有一定的抑制活性,平均抑制率分别为41.4%、47.2%、69.1%、68.3%和50.2%。目标化合物5a~5m对苹果轮纹病菌和番茄早疫病菌的抑制效果较好,平均抑制率分别达69.1%和68.3%,其中半数以上化合物的抑制率在70%~90%之间。化合物5f(R=p-FAr)对苹果轮纹病菌的抑制率达90.0%(活性级别为A级[23],接近阳性对照嘧菌酯),化合物5b(R=C(CH3)3)、5c(R=环己基)、5d(R=Ar)、5g(R=o-CH3Ar)、5i(R=p-CH3Ar)、5j(R=m-OCH3Ar)对苹果轮纹病菌的抑制活性级别均达B级;化合物5d(R=Ar)对番茄早疫病菌的抑制率达91.8%(活性级别为A级,接近阳性对照嘧菌酯),化合物5a(R=CH3)、5b(R=C(CH3)3)、5c(R=环己基)、5f(R=p-FAr)、5h(R=m-CH3Ar)、5j(R=m-OCH3Ar)对番茄早疫病菌的抑制活性级别均达B级。与原料紫苏醛相比,大部分紫苏醛基席夫碱-(硫)脲目标化合物的抑菌活性有明显提高。总体上,取代苯基硫脲类目标化合物的抑菌活性优于取代苯基脲类目标化合物。
表1 化合物5a~5m的抑菌活性Table 1 Antifungal activity of compounds 5a-5m
1)*:阳性对照positive control 下表同same as in following table
2.2.2 除草活性 由表2可知,在质量浓度100 mg/L下,大部分目标化合物对油菜的胚根生长显示一定的抑制作用,平均抑制率为44.6%,其中,化合物5a(R=CH3)、5c(R=环己基)和5i(R=p-CH3Ar)的抑制率分别为67.4%、77.6%和75.3%(活性级别为B级[24]),优于阳性对照丙炔氟草胺。部分紫苏醛基席夫碱-(硫)脲目标化合物的除草活性较原料紫苏醛有明显的增强作用。总体上,取代苯基硫脲类目标化合物的除草活性优于取代苯基脲类目标化合物。
表2 化合物5a~5m的除草活性Table 2 Herbicidal activity of compounds 5a-5m
3.1 以紫苏醛为原料,经3步反应,合成得到13个未见文献报道的紫苏醛基席夫碱-(硫)脲化合物(5a~5m),并利用FT-IR、1H NMR、13C NMR 和ESI-MS等多种手段对目标产物进行了分析和表征。
3.2 初步的生物活性测试表明,50 mg/L的目标化合物对5种供试植物病原菌均有一定的抑制作用,其中化合物5f(R=p-FAr)对苹果轮纹病菌的抑制率达90.0%(接近阳性对照嘧菌酯),化合物5d(R=Ar)对番茄早疫病菌的抑制率达91.8%(接近阳性对照嘧菌酯)。目标化合物对油菜的胚根生长具有一定的抑制作用,在质量浓度100 mg/L条件下,其中化合物5c(R=环己基)、5i(R=p-CH3Ar)和5a(R=CH3)的抑制率分别为77.6%、75.3%和67.4%(优于阳性对照丙炔氟草胺)。总体上,取代苯基硫脲类目标化合物的抑菌和除草活性优于取代苯基脲类目标化合物。
致谢:抑菌和除草活性测试由南开大学元素有机化学研究所生物活性测试室测定,谨表谢意。
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Synthesis and Biological Activities of Perillaldehyde-based Schiff Base-(thio)urea Compounds
MA Yuan1, DUAN Wengui1, LIN Guishan1, LIU Luzhi1, HUANG Zhengsong1, LEI Fuhou2
(1.College of Chemistry and Chemical Engineering,Guangxi University, Nanning 530004, China; 2.Guangxi KeyLaboratory of Chemistry and Engineering of Forest Products, Nanning 530008, China)
Thirteen novel perillaldehyde-based Schiff base-(thio)urea compounds (5a-5m) were designed and synthesized by using perillaldehyde as starting material. Their structures were analyzed and characterized by FT-IR,1H NMR,13C NMR, and ESI-MS. The results of preliminary bioassay showed that, at the mass concentration of 50 mg/L, the inhibition rate of target compound 5f (R=p-FAr) againstPhysalosporapiricolawas 90.0% (close to that of the positive control azoxystrobin), and the inhibition rate of target compound 5d (R=Ar) againstAlternariasolaniwas 91.8% (close to that of the positive control azoxystrobin). Besides, at the mass concentration of 100 mg/L, the target compounds 5c (R=cyclopentyl), 5i (R=p-CH3Ar) and 5a (R=CH3) exhibited 77.6%, 75.3% and 67.4% inhibition against the growth of rape (Brassicacampestris) root, respectively (greater than positive control flumioxazin). Furthermore, substituted phenyl thioureas showed better antifungal and herbicidal activities than substituted phenyl ureas.
perillaldehyde;Schiff base-(thio)urea;synthesis;antifungal activity;herbicidal activity
10.3969/j.issn.0253-2417.2017.01.007
2016- 04- 05
国家自然科学基金资助项目(31460173);广西林产化学与工程重点实验室开放基金资助项目(GXFC15- 01);广西大学“大学生创新创业训练计划”资助项目(201510593002)
马 媛(1990— ),女,宁夏中卫人,硕士生,从事天然产物改性及有机合成的研究
*通讯作者:段文贵,教授,博士生导师,主要从事天然资源化学和有机合成的研究;E-mail:wgduan@gxu.edu.cn。
TQ351
A
0253-2417(2017)01- 0054- 09
马媛,段文贵,林桂汕,等.紫苏醛基席夫碱-(硫)脲化合物的合成及生物活性[J].林产化学与工业,2017,37(1):54-62.