CN103626652A - 3-芳基丙烯酸及其衍生物抗植物病毒剂 - Google Patents

3-芳基丙烯酸及其衍生物抗植物病毒剂 Download PDF

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CN103626652A
CN103626652A CN201210310324.6A CN201210310324A CN103626652A CN 103626652 A CN103626652 A CN 103626652A CN 201210310324 A CN201210310324 A CN 201210310324A CN 103626652 A CN103626652 A CN 103626652A
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different substituents
ring
virus
carbon
acrylic acid
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CN103626652B (zh
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汪清民
吴萌
王兹稳
孟垂松
王开亮
呼艳娜
王力钟
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Nankai University
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Abstract

本发明涉及如通式(I)所示的3-芳基丙烯酸及其衍生物在农药上的应用，用作新型抗植物病毒剂，能很好地抑制烟草花叶病毒、辣椒病毒、番茄病毒、甘薯病毒、马铃薯病毒和瓜类病毒及玉米矮花叶病毒等，可有效防治烟草、辣椒、番茄、瓜菜、粮食、蔬菜、豆类等多种作物的病毒病，尤其适合于防治烟草花叶病。(其中Ar和R的意义见说明书)

Description

3-芳基丙烯酸及其衍生物抗植物病毒剂
技术领域
本发明涉及一类新型抗植物病毒剂及其应用，具体涉及3-芳基丙烯酸及其衍生物作为抗植物病毒剂，3-芳基丙烯酸及其衍生物与具有抗植物病毒活性成分的互作组合物作为抗植物病毒剂，以及它们在防治植物病毒病上的应用，属农药技术领域。
背景技术
3-芳基丙烯酸是一种重要的有机合成中间体，广泛应用于香料、医药、农药、甜味剂、塑料和感光树脂等方面。它是某些植物生命活动中不可缺少的生长调节剂，在植物细胞生长分裂中起着重要作用，其衍生物广泛存在于天然药物中。据文献报道，3-苯基丙烯酸类衍生物具有多种生物与药理活性，比如抗炎抗癌活性(张琳萍等，药学学报，1992，27(11)，817-823.)，杀虫活性(Park et al.，J.Agric.Food Chem.，2000，48，2528-2531.)，杀菌活性(Miyazawa et al.，J.Agric.Food Chem.，1998，46，904-910；Lee et.al.，J.Agric.Food Chem.，2001，49，4656-4661；Walker et al.，J. Agric.Food Chem.，2003，51，2548-2554.)等等。
Figure BSA00000769588000011
结构式一
3-芳基丙烯酸中最典型的代表是反式阿魏酸(1，结构式一)，它最初是在植物的种子和叶子中发现的，是一种广泛存在于植物中的酚酸，在细胞壁中与多糖和蛋白质结合成为细胞壁的骨架，它在阿魏、当归、川芎、升麻、酸枣仁等中药材中的含量较高，是这些中药的有效成分之一，已经作为中成药的质量指标之一。阿魏酸毒性低，雄鼠的LD50为2445mg/kg，雌鼠的LD50为2113mg/kg。阿魏酸在食品领域中的应用广泛，它可以调节人体免疫力，能活血通络，消除黄褐斑、失眠、腰酸腿沉等症。阿魏酸在化妆品中也有广泛的应用，它能改善皮肤品质，使其细腻、光泽、富有弹性，阿魏酸及其衍生物被公认为美容因子。反式阿魏酸还具有多种生物活性，如具有抗血小板凝聚、抑制5-羟色胺的释放、缓解血管痉挛和镇痛等作用，体外抗氧化作用，抗血栓、降血脂，防治冠心病等等(欧仕益，广州食品工业科技，2002，4，50-53.)。还有文献报道过阿魏酸对细菌的抑制作用，其具有抗菌消炎的作用(Lo and Chung，Anticancer Res.，1999，19，133-139.)。Kawabata等还报道了阿魏酸的抗癌活性(Kawabata et al.，Cancer Lett.，2000，157，15-21.)。反式肉桂酸(5，结构式一)也是其中的典型代表，有文献报道过其具有植物化感活性(Chaves et al.，J.Chem.Ecol.，2001，27，611-621.)和杀虫活性(Park et al.，J.Agric.Food Chem.，2000，48，2528-2531.)。芥子酸(结构式一)对肝癌细胞则具有很好的抗癌活性(IC50＝14μM)(Zou et al.，Bioorg.Med.Chem.，2006，14，2060-2071.)。
目前，除了3-芳基丙烯酸可作为食品、粮食防腐剂在农业上的相关应用以外，有关3-芳基丙烯酸及其衍生物在农业上用于抗植物病毒病活性的研究仅有本课题组一例(WO2011/069444A1)。我们首次发现天然阿魏酸及其衍生物如1-13(结构式一)具有抗植物病毒活性，但研究还处于初步阶段，结构类型比较单一，仅仅局限于3-苯基的丙烯酸类衍生物。为了创制新型高效低毒的抗植物病毒剂，还须拓展结构类型，进行系统的结构改造和深入的构效关系研究。
由于植物病毒病种类繁多(常见种类2000余种)，防治极为困难，素有“植物癌症”之称，其危害仅次于真菌病害，给农业生产已造成极大损失。据统计，全世界每年农作物因此造成的经济损失达200亿美元，其中仅烟草花叶病毒(Tobacco mosaic virus，TMV)每年造成的经济损失超过1亿美元(Bos L.Trends in microbiology，2000，8(2)，82-87)。抗植物病毒药剂的需求和开发一直受到很大关注，已发现的抗植物病毒药剂主要有(表1)：苯并噻二唑(BTH)、噻酰菌胺(TDL)、4-甲基-1，2，3-噻二唑-5-甲酸(TDLA)、DL-β-氨基丁酸(BABA)、病毒唑、宁南霉素、菲并吲哚里西啶生物碱安托芬、联三唑类化合物XY-13和XY-30、病毒A(有效成分为盐酸吗啉双胍和醋酸铜)、水杨酸、多羟基双萘醛、氨基寡糖素(几丁寡糖，学名为β-1，4-寡聚葡萄糖胺)。而现有的这些抗植物病毒剂中实用化品种并不多，而且防治效果差，一般低于60％，质量控制较为困难，长期使用都存在一定的环境风险。因此，开发以天然植物活性物质为有效成分的高效、低毒的绿色抗植物病毒农药新品种意义非常重大。
表1.部分具有抗病毒活性化合物的化学结构
发明内容
本发明目的在于提供一类新型、高效、低毒的抗植物病毒剂及其抗植物病毒应用。本发明在前期首次发现天然阿魏酸及其衍生物具有抗植物病毒活性(WO 2011/069444 A1)的基础上，拓展结构类型，进行系统的结构改造，发现系列3-芳基丙烯酸都表现出很好的抗病毒活性，且部分化合物活体活性明显优于天然阿魏酸及其衍生物。本发明为创制新型高效的抗植物病毒剂奠定了基础，在原工作基础上更进一步，取得了实质性的进展。
本发明抗植物病毒剂有效成分为3-芳基丙烯酸及其衍生物，其结构通式为(I)所示结构的化合物：
Figure BSA00000769588000032
式中，Ar代表含不同取代基的苯环、含不同取代基的萘环、含不同取代基的菲环、含不同取代基的蒽环、含不同取代基的芘环、含不同取代基的喹啉环、含不同取代基的呋喃环、含不同取代基的吡唑环、含不同取代基的咔唑环、含不同取代基的吡啶环，含不同取代基的吡唑环，含不同取代基的噻唑环，含不同取代基的噻吩环，含不同取代基的噁唑环；R代表氢、羟基、ONa、OK、ONH4、葡萄糖基、烃氧基、烃胺基、二烃胺基、1-6碳烃基、(3-6)碳烯基、(3-6)卤代碳烯基、(3-6)碳炔基、1-4碳卤代烷基、1-4碳烷氧烷基、1-4碳烷硫烷基、苯基、萘基、色满、2，3-二氢-1，4-苯并二噁嗪、4H-1，3-苯并二噁嗪、2，3-二氢-苯并呋喃、苯并呋喃、苯并噻唑、1，3-苯并噁唑、1，2-苯并异噁唑或苯并咪唑，各基团是未取代的，或是被一个或一个以上下述基团取代：卤素、1-4碳烷基、1-4碳烷氧基、1-4碳卤代烷基、1-4碳卤代烷氧基、1-4碳烷氧烷基、1-4碳烷硫基、1-4碳烷基亚磺酰基、1-4碳烷基磺酰基、硝基、氰基、羟基、羧基、1-4碳烷基羰基、1-4碳烷氧基羰基或亚胺基。双键的构型为反式、或顺式、或顺反混合。
本发明所述的3-芳基丙烯酸及其衍生物是如下结构式二中所示结构14-31为代表的化合物。
Figure BSA00000769588000041
结构式二
本发明通式(I)的化合物具有优异的抗植物病毒活性，能很好地抑制烟草花叶病毒、辣椒病毒、番茄病毒、甘薯病毒、马铃薯病毒和瓜类病毒及玉米矮花叶病毒等，可有效防治烟草、辣椒、番茄、瓜菜、粮食、蔬菜、豆类等多种作物的病毒病，尤其适合于防治烟草花叶病。
本发明通式(I)的部分化合物如22和23在500μg/mL的浓度下对烟草花叶病毒的活体钝化、治疗和保护活性分别为22：45.0％、46.2％，49.7；23：48.8％、42.5％、46.6％。活性明显超过商品化品种病毒唑(活体钝化、治疗和保护：35.9％、32.3％、36.4％)和前期发现的反式阿魏酸(1，活体钝化、治疗和保护，38.5％、31.2％、34.3％)。
本发明通式(I)的化合物作为植物病毒抑制剂可以直接使用，也可以加上农业上接受的载体使用，也可以和其他抗植物病毒剂如苯并噻二唑(BTH)、噻酰菌胺(TDL)、4-甲基-1，2，3-噻二唑-5-甲酸(TDLA)、DL-β-氨基丁酸(BABA)、病毒唑、宁南霉素、菲并吲哚里西啶生物碱安托芬、联三唑类化合物XY-13和XY-30、病毒A、水杨酸、多羟基双萘醛、氨基寡糖素形成互作组合物使用，这些组合物有的表现增效作用，有的表现相加作用。
本发明的3-芳基丙烯酸及其衍生物抗植物病毒剂较现有使用的病毒抑制剂，具有很大的优势：化学结构简单，抗植物病毒活性显著，且对多种植物病毒具有抑制作用；毒性极低，环境兼容性好，对非靶标生物安全。
具体实施方式
以下通过实施例对本发明作进一步的详细说明，但本发明不限于这些实施例。
实施例1：3-芳基丙烯酸14-22和24-29的合成：
Figure BSA00000769588000051
将芳香醛(2.16mmol)，丙二酸(0.45g，4.32mmol)，哌啶(2.0mL)，吡啶(20mL)的混合液加热回流反应3-40h。冷至室温，向反应液中25％K2CO3溶液，搅拌下加热，分液，水相用稀盐酸进行酸化，过滤，干燥可得粗产品，经过重结晶或者柱层析可得纯品。
(E)-3-(2-呋喃基)丙烯酸(14)
柱层析纯化(石油醚∶乙酸乙酯＝2∶1)得黄色固体，收率66％。熔点143-144℃；1H NMR(400MHz，CDCl3)：δ7.53(d，3JHH＝15.6Hz，1H)，7.52(d，J＝1.6Hz，1H)，6.68(d，J＝3.6Hz，1H)，6.50(dd，J＝3.6Hz，1.6Hz，1H)，6.32(d，J＝15.6Hz，1H).
(E)-3-(2-噻吩基)丙烯酸(15)
柱层析纯化(石油醚∶乙酸乙酯＝2∶1)得黄色固体，收率69％。熔点145-148℃；1H NMR(400MHz，CDCl3)：δ7.89(d，J＝15.6Hz，1H)，7.52(d，J＝5.2Hz，1H)，7.31(d，J＝3.2Hz，1H)，7.08(dd，J＝5.2Hz，3.2Hz，1H)，6.25(d，J＝15.6Hz，1H).
(E)-3-(2-吡啶基)丙烯酸(16)
反应结束后冷至0℃，加入乙醚(40ml)过滤，得黄色固体16，收率65％。熔点199-201℃；1H NMR(400MHz，DMSO-d6)：δ12.63(s，1H)，8.64(d，3JHH＝4.0Hz，1H)，7.52(td，J＝7.6Hz，J＝1.6Hz，1H)，7.60(d，J＝15.6Hz，1H)，7.08(dd，J＝7.2Hz，4.8Hz，1H)，6.83(d，J＝15.6Hz，1H).13C NMR(100MHz，DMSO-d6)：δ167.3，152.4，150.0，143.1，137.2，124.6，124.5，122.7.HRMS(ESI)：calcd.for C8H8NO2[M+H]+150.0550；found 150.0550.
(E)-3-(3-吡啶基)丙烯酸(17)
反应结束后冷至0℃，加入乙醚(40ml)过滤，得黄色固体17，收率82％。熔点236-238℃；1H NMR(400MHz，DMSO-d6)：δ8.86(s，1H)，8.59(d，J＝4.4Hz，1H)，8.16(d，J＝7.6Hz，1H)，7.62(d，J＝8.4Hz，1H)，7.44-7.47(m，1H)，6.71(d，J＝8.4Hz，1H).
(E)-3-(4-吡啶基)丙烯酸(18)
反应结束后冷至0℃，加入乙醚(40ml)过滤，得黄色固体18，收率87％。熔点277-279℃；1H NMR(400MHz，DMSO-d6)：δ12.78(s，1H)，8.62(d，J＝6.0Hz，2H)，7.66(d，J＝6.0Hz，2H)，7.56(d，J＝16.0Hz，1H)，6.80(d，J＝16.0Hz，1H).
(E)-3-(2-噻唑基)丙烯酸(19)
柱层析纯化(石油醚∶乙酸乙酯＝2∶1)得白色固体，收率80％。熔点186-189℃；1H NMR(400MHz，DMSO-d6)：δ12.81(s，1H)，8.01(d，J＝3.2Hz，1H)，7.94(d，J＝3.2Hz，1H)，7.70(d，J＝15.6Hz，1H)，6.67(d，J＝15.6Hz，1H).13C NMR(100MHz，DMSO-d6)：δ166.7，162.7，144.7，135.2，123.5，123.4.HRMS(ESI)：calcd.for C6H6NO2S[M+H]+156.0114；found 156.0112.
(E)-3-(5-甲基-3-异恶唑基)丙烯酸(20)
柱层析纯化(石油醚∶乙酸乙酯＝2∶1)得白色固体，收率64％。熔点184-185℃；1H NMR(400MHz，DMSO-d6)：δ12.89(s，1H)，7.41(d，J＝16.0Hz，1H)，6.77(s，1H)，6.69(d，J＝15.6Hz，1H)，2.44(s，3H).
(E)-3-(3-甲基-1-苯基-5-氯-4-吡唑基)丙烯酸(21)
用乙酸乙酯重结晶得白色固体，收率64％。熔点202-203℃；1H NMR(400MHz，CDCl3)：δ7.73(d，J＝16.0Hz，1H)，7.45-7.56(m，5H)，6.42(d，J＝16.0Hz，1H)，2.48(s，3H).13C NMR(100MHz，CDCl3)：δ172.5，150.1，137.7，135.9，129.3，129.0，128.9，125.2，116.1，113.7，14.4.HRMS(ESI)：calcd.for C13H12ClN2O2[M+H]+263.0582；found 263.0579.
(E)-3-(7-苯并[1，2，3]噻二唑基)丙烯酸(22)
白色固体，收率64％。熔点212-214℃；1H NMR(400MHz，DMSO-d6)：δ12.87(s，1H)，8.85(d，J＝8.0Hz，1H)，8.85(d，J＝7.2Hz，1H)，7.95(d，J＝16.0Hz，1H)，7.89(t，J＝7.6Hz，1H)，6.46(d，J＝16.0Hz，1H).13C NMR(100MHz，DMSO-d6)：δ166.7，158.9，141.4，138.0，131.9，128.4，127.4，125.5，123.0.HRMS(ESI)：calcd.for C9H7N2O2S[M+H]+207.0223；found 207.0220.
(E)-3-(6-羟基-2-萘基)丙烯酸(24)
用乙醚洗涤可得白色固体，收率73％。熔点238-240℃；1H NMR(400MHz，DMSO-d6)：δ8.03(s，1H)，7.80(d，J＝8.8Hz，1H)，7.75(dd，J＝8.8Hz，1.6Hz，1H)，7.66-7.71(m，2H)，7.10-7.14(m，2H)，6.55(d，J＝16.0Hz，1H).13C NMR(100MHz，DMSO-d6)：δ167.9，156.7，144.3，135.6，130.3，129.8，128.8，127.4，126.8，124.2，119.3，117.9，109.0.HRMS(ESI)：calcd.forC13H11O3[M+H]+215.0703；found 215.0700.
(E)-3-(2，3，6，7-四甲氧基-9-菲)丙烯酸(25)
乙醇重结晶得黄色固体，收率70％。熔点269-271℃；1H NMR(400MHz，DMSO-d6)：δ12.54(s，1H)，8.36(d，J＝15.6Hz，1H)，8.08(s，1H)，8.06(s，1H)，7.99(s，1H)，7.47(s，1H)，7.46(s，1H)，6.60(d，J＝15.6Hz，1H)，4.05(s，6H)，3.97(s，3H)，3.92(s，3H).13C NMR(100MHz，DMSO-d6)：δ167.6，150.1，149.1，148.8，148.8，141.6，127.0，125.3，125.3，124.4，123.9，123.8，120.7，108.9，104.3，104.0，103.5，56.0，55.9，55.4，55.4.HRMS(ESI)：calcd.for C21H21O6[M+H]+369.1333；found 339.1336.
(E)-3-(3，6，7-三甲氧基-9-菲)丙烯酸(26)
乙醇重结晶得黄色固体，收率77％。熔点277-280℃；1H NMR(400MHz，DMSO-d6)：δ12.52(s，1H)，8.36(d，J＝15.6Hz，1H)，8.15(s，1H)，8.13(s，1H)，8.08(d，J＝2.0Hz，1H)，7.94(d，J＝8.8Hz，1H)，7.49(s，1H)，7.26(dd，J＝8.8Hz，2.0Hz，1H)，6.63(d，J＝15.6Hz，1H)，4.06(s，3H)，4.02(s，3H)，3.99(s，3H).13C NMR(100MHz，DMSO-d6)：δ167.6，158.9，149.5，149.0，141.5，131.7，130.9，126.7，124.9，124.9，124.5，124.2，120.9，116.5，104.7，104.0，104.0，55.9，55.6，55.4.HRMS(ESI)：calcd.for C20H19O5[M+H]+339.1227；found 339.1227.
(E)-3-(2，3-二甲氧基-6-苄氧基-9-菲)丙烯酸(27)
乙醇重结晶得黄色固体，收率76％。熔点196-197℃；1H NMR(400MHz，DMSO-d6)：δ
12.52(s，1H)，8.35(d，J＝15.6Hz，1H)，8.25(d，J＝2.4Hz，1H)，8.12(d，J＝9.2Hz，1H)，8.08(s，1H)，8.05(s，1H)，7.59(d，J＝7.2Hz，2H)，7.51(s，1H)，7.44(t，J＝7.2Hz，2H)，7.34-7.40(m，2H)，6.59(d，J＝15.6Hz，1H)，5.39(s，2H)，4.06(s，3H)，3.93(s，3H).13C NMR(100MHz，DMSO-d6)：δ167.6，157.1，150.1，149.6，141.3，137.1，131.1，128.5，128.1，128.0，127.5，126.4，125.4，125.0，123.5，123.4，120.9，116.5，109.0，106.3，104.0，69.7，56.0，55.5.HRMS(ESI)：calcd.for C26H23O5[M+H]+415.1540；found 415.1543.
(E)-3-(6-羟基-2，3-二甲氧基-9-菲)丙烯酸(28)
柱层析纯化(二氯甲烷∶甲醇＝25∶1)得黄色固体，收率68％。熔点239-241℃；1H NMR(400MHz，DMSO-d6)：δ12.51(s，1H)，9.89(s，1H)，8.34(d，J＝15.6Hz，1H)，8.04(d，J＝9.6Hz，2H)，8.00(s，1H)，7.92(s，1H)，7.48(s，1H)，7.19(d，J＝8.8Hz，1H)，6.57(d，J＝15.6Hz，1H)，4.03(s，3H)，3.92(s，3H).13C NMR(100MHz，DMSO-d6)：δ168.7，157.4，151.0，150.6，142.6，132.5，128.8，127.5，126.4，125.9，123.7，123.5，121.8，118.1，110.2，108.0，104.7，56.8，56.7.HRMS(ESI)：calcd.for C19H17O5[M+H]+325.1071；found 325.1072.
(E)-3-(3-羟基-6，7-二甲氧基-9-菲)丙烯酸(29)
柱层析纯化(二氯甲烷∶甲醇＝25∶1)得黄色固体，收率65％。熔点239-241℃；1H NMR(400MHz，DMSO-d6)：δ12.48(s，1H)，9.99(s，1H)，8.34(d，J＝15.6Hz，1H)，8.08(s，1H)，7.98(s，1H)，7.95(d，J＝1.6Hz，2H)，7.86(d，J＝8.8Hz，1H)，7.47(s，1H)，7.13(dd，J＝8.8Hz，2.0Hz，1H)，6.60(d，J＝15.6Hz，1H)，4.02(s，3H)，3.98(s，3H).13C NMR(100MHz，DMSO-d6)：δ167.6，157.3，149.4，148.8，141.5，132.0，131.0，125.7，124.8，123.9，123.8，120.4，117.1，106.0，104.2，104.0，55.6，55.4.HRMS(ESI)：calcd.for C19H17O5[M+H]+325.1071；found 325.1075.
实施例2：(E)-3-(2-羟基-1-萘基)丙烯酸(23)的合成
Figure BSA00000769588000081
将乙氧甲酰基甲基三苯基溴化膦(3.73g，8.72mmol)和2-羟基-1-萘甲醛(1.50g，8.72mmol)甲醇溶液(20mL)缓慢加入碳酸钾(2g)的甲醇(20mL)溶液中，该反应液在室温下搅拌6h，然后浓缩。加入二氯甲烷(50mL)和水(50mL)，分液，水相用二氯甲烷萃取，合并有机相，用无水硫酸钠干燥，过滤，浓缩得到粗产品。将该粗产品加入到2mol/L氢氧化钾(30mL)中搅拌2h。加入二氯甲烷(50mL)，分液，水相2mol/L的稀盐酸酸化，过滤，水洗，干燥得白色固体24(1.34g)，收率72％。熔点179-180℃；1H NMR(400MHz，DMSO-d6)：δ12.32(s，1H)，10.75(s，1H)，8.24(d，J＝16.0Hz，1H)，8.10(d，J＝8.0Hz，1H)，7.85(d，J＝8.0Hz，2H)，7.55(br，1H)，7.36(br，1H)，7.28(d，J＝8.4Hz，1H)，6.82(d，J＝16.0Hz，1H).
实施例3：(E)-3-(7-苯并[1，2，3]噻二唑基)丙烯酸甲酯(30)和(E)-3-(2-羟基-1-萘基)丙烯酸甲酯(31)的合成
Figure BSA00000769588000091
将(E)-3-芳基丙稀酸22或23(2mmol)溶于甲醇(25mL)，在室温下加入浓硫酸(0.72g)，加热回流8h。冷至室温，加入二氯甲烷(50mL)和水(50mL)，分液，水相用二氯甲烷萃取，合并有机相，用碳酸氢钠洗有机相，无水硫酸钠干燥，过滤，浓缩得到产品。
(E)-3-(7-苯并[1，2，3]噻二唑基)丙烯酸甲酯(30)
白色固体，收率94％。熔点118-120℃。1H NMR(400MHz，CDCl3)：δ8.70(d，J＝8.4Hz，1H)，7.95(d，J＝16.0Hz，1H)，7.84(d，J＝7.2Hz，1H)，7.73(t，J＝8.0Hz，1H)，6.46(d，J＝16.0Hz，1H)，3.88(s，3H).13C NMR(100MHz，CDCl3)：δ166.7，159.6，142.3，138.8，131.5，127.8，125.9，122.0，77.5，77.2，76.8，52.3.
(E)-3-(2-羟基-1-萘基)丙烯酸甲酯(31)
白色固体，收率96％。熔点166-168℃。1H NMR(400MHz，CDCl3)：δ8.33(d，J＝16.4Hz，1H)，8.02(d，J＝8.8Hz，1H)，7.76-7.79(m，2H)，7.53(t，J＝7.6Hz，1H)，7.39(t，J＝7.6Hz，1H)，7.14(d，J＝8.8Hz，1H)，6.76(d，J＝16.4Hz，1H)，6.07(s，1H)，3.89(s，1H).13C NMR(100MHz，CDCl3)：δ168.0，152.8，138.7，132.7，131.6，129.0，128.7，127.5，123.9，123.2，123.0，118.0，113.9，52.0.HRMS(ESI)：calcd.for C14H13O3[M-H]-227.0714；found 227.0710.
实施例4：生物活性以抗烟草花叶病毒(Tobacco mosaic virus，TMV)活性为例，
3-芳基丙烯酸及其衍生物抗烟草花叶病毒活性的测定程序如下：
1、病毒提纯及浓度测定：
病毒提纯及浓度测定参照南开大学元素所生测室编制烟草花叶病毒SOP规范执行。病毒粗提液经2次聚乙二醇离心处理后，测定浓度，4℃冷藏备用。
2、化合物溶液配制：
称量后，原药加入DMF溶解，制得1×105μg/mL母液，后用含1‰吐温80水溶液稀释至所需浓度；病毒唑制剂直接兑水稀释。
3、离体作用：
摩擦接种珊西烟适龄叶片，用流水冲洗，病毒浓度10μg/mL。收干后剪下，沿叶中脉对剖，左右半叶分别浸于1‰吐温水及药剂中，30min后取出，于适宜光照温度下保湿培养，每3片叶为1次重复，重复3次。3d后记录病斑数，计算防效。
4、活体保护作用：
选长势均匀一致的3-5叶期珊西烟，全株喷雾施药，每处理3次重复，并设1‰吐温80水溶液对照。24h后，叶面撒布金刚砂(500目)，用毛笔蘸取病毒液，在全叶面沿支脉方向轻擦2次，叶片下方用手掌支撑，病毒浓度10μg/mL，接种后用流水冲洗。3d后记录病斑数，计算防效。
5、活体治疗作用：
选长势均匀一致的3-5叶期珊西烟，用毛笔全叶接种病毒，病毒浓度为10μg/mL，接种后用流水冲洗。叶面收干后，全株喷雾施药，每处理3次重复，并设1‰吐温80水溶液对照。3d后记录病斑数，计算防效。
6、活体钝化作用：
选长势均匀一致的3-5叶期珊西烟，将药剂与等体积的病毒汁液混合钝化30min后，摩擦接种，病毒浓度20μg/mL，接种后即用流水冲洗，重复3次，设1‰吐温80水溶液对照。3d后数病斑数，计算结果。
抑制率(％)＝[(对照枯斑数-处理枯斑数)/对照枯斑数]×100％
表1为部分化合物的抗烟草花叶病毒(Tobacco mosaic virus，TMV)活性测试结果：
(表中化合物1-13以及商品化品种病毒唑用于对照衬托本发明化合物的活性)
Figure BSA00000769588000111
Figure BSA00000769588000121
Figure BSA00000769588000131
通过表1中数据可以看出，大部分3-芳基丙烯酸及其衍生物都表现出很好的抗烟草花叶病毒活体活性。含有苯并噻二唑的芳基丙烯酸22表现出极高的活性，在四种模式下其活性高于病毒唑，其中在500μg/mL的浓度下，4种模式下的活性都在45％以上。含有萘环的芳基丙烯酸23也表现出了非常好的活性，500μg/mL的浓度下，4种模式下的活性都在40％以上，高于病毒唑，而且其对应的酯39的活性也是高于病毒唑，而略微低于23的活性。含有菲环的芳基丙烯酸25-29在500μg/mL的浓度下和病毒唑的活性相当，其中活性较好的是25和27。

Claims (6)

1.3-芳基丙烯酸及其衍生物抗植物病毒剂，其特征在于它具有如下通式(I)所示结构：
Figure FSA00000769587900011
式中，Ar代表含不同取代基的苯环、含不同取代基的萘环、含不同取代基的菲环、含不同取代基的蒽环、含不同取代基的芘环、含不同取代基的喹啉环、含不同取代基的呋喃环、含不同取代基的吡唑环、含不同取代基的咔唑环、含不同取代基的吡啶环，含不同取代基的吡唑环，含不同取代基的噻唑环，含不同取代基的苯并[1，2，3]噻二唑基，含不同取代基的噻吩环，含不同取代基的噁唑环；R代表氢、羟基、ONa、OK、ONH4、葡萄糖基、烃氧基、烃胺基、二烃胺基、1-6碳烃基、(3-6)碳烯基、(3-6)卤代碳烯基、(3-6)碳炔基、1-4碳卤代烷基、1-4碳烷氧烷基、1-4碳烷硫烷基、苯基、萘基、色满、2，3-二氢-1，4-苯并二噁嗪、4H-1，3-苯并二噁嗪、2，3-二氢-苯并呋喃、苯并呋喃、苯并噻唑、1，3-苯并噁唑、1，2-苯并异噁唑或苯并咪唑，各基团是未取代的，或是被一个或一个以上下述基团取代：卤素、1-4碳烷基、1-4碳烷氧基、1-4碳卤代烷基、1-4碳卤代烷氧基、1-4碳烷氧烷基、1-4碳烷硫基、1-4碳烷基亚磺酰基、1-4碳烷基磺酰基、硝基、氰基、羟基、羧基、1-4碳烷基羰基、1-4碳烷氧基羰基或亚胺基；双键的构型为反式、或顺式、或顺反混合。
2.根据权利要求1所述的3-芳基丙烯酸及其衍生物抗植物病毒剂，其特征在于Ar代表含不同取代基的苯环、萘环、菲环、呋喃环、吡唑环、吡啶环、吡唑环、噻唑环、苯并[1，2，3]噻二唑基、噻吩环、噁唑环；R代表OH，OCH3；双键的构型为反式、或顺式、或顺反混合。
3.根据权利要求1和2所述的3-芳基丙烯酸及其衍生物抗植物病毒剂，其特征在于优选的通式I所示的化合物是(E)-3-(7-苯并[1，2，3]噻二唑基)丙烯酸(22)和(E)-3-(2-羟基-1-萘基)丙烯酸(23)。
4.权利要求1所述的3-芳基丙烯酸及其衍生物抗植物病毒剂，其特征在于它作为抗植物病毒剂，能很好地抑制烟草花叶病毒、辣椒病毒、番茄病毒、甘薯病毒、马铃薯病毒和瓜类病毒及玉米矮花叶病毒等，可有效防治烟草、辣椒、番茄、瓜菜、粮食、蔬菜、豆类等多种作物的病毒病，尤其适合于防治烟草花叶病。
5.权利要求1所述的3-芳基丙烯酸及其衍生物抗植物病毒剂，其特征在于它作为抗植物病毒剂直接使用。
6.权利要求1所述的3-芳基丙烯酸及其衍生物抗植物病毒剂，其特征在于它作为抗植物病毒剂和其他抗植物病毒剂如苯并噻二唑(BTH)、噻酰菌胺(TDL)、4-甲基-1，2，3-噻二唑-5-甲酸(TDLA)、DL-β-氨基丁酸(BABA)、病毒唑、宁南霉素、菲并吲哚里西啶生物碱安托芬、联三唑类化合物XY-13和XY-30、病毒A、水杨酸、多羟基双萘醛、氨基寡糖素形成互作组合物使用。
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CN104886078A (zh) * 2015-05-08 2015-09-09 长阳勤劳农夫农产品有限公司 一种铁皮石斛种苗的抗性诱导剂
CN107216282A (zh) * 2017-05-16 2017-09-29 南开大学 一种α‑氨基丙烯酸类杀微生物剂及其制备方法和用途
CN107216282B (zh) * 2017-05-16 2020-07-03 南开大学 一种α-氨基丙烯酸类杀微生物剂及其制备方法和用途
CN113801022A (zh) * 2021-07-23 2021-12-17 贵州大学 阿魏酸丁香酚及异丁香酚杂合体及应用
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