CN110483405B - Kealiinine类衍生物及其制备和在抗植物病毒和病菌中的应用 - Google Patents
Kealiinine类衍生物及其制备和在抗植物病毒和病菌中的应用 Download PDFInfo
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Abstract
本发明涉及Kealiinine类衍生物II及其制备方法和在抗植物病毒和病菌中的应用。本发明的Kealiinine类衍生物II显示出特别优异的抗植物病毒活性,能很好地抑制烟草花叶病毒(TMV),该类化合物同时表现出一定的抗植物病菌活性。
Description
技术领域
本发明涉及Kealiinine类衍生物及其制备和在抗植物病毒和病菌中的应用,属于农业防护技术领域。
背景技术
海洋是地球上最大的资源宝库,其独特的海洋环境(高盐、高压、缺氧、低(恒)温、低(无)光照)产生了生物活性多样、结构丰富的海洋天然产物。到目前为止,已发现海洋生物来源的天然产物超过2.5万种,并且这一数目还在以平均每年1000种的数量增长(Nat.Prod.Rep.2014,31(2):160-258.;Nat.Prod.Rep.2017,34(3):235-294.)。在医药领域,许多海洋天然产物展现出了优异的抗肿瘤、抗菌、抗病毒、抗心血管疾病等药用活性(承德医学院学报,2017,34(4):332-336.);在农用活性方面,也表现出杀虫、除草、抗农业病菌的作用(J.Agric.Food Chem.2003,51,2246-2252.)。因此,从海洋天然产物中发现活性先导化合物已经成为众多科学家们的研究热点。
Kealiinine类生物碱是一类具有萘并2-氨基咪唑平面结构的海洋天然产物,是Leucetta生物碱的重要组成部分。2004年,Proksch课题组(J.Nat.Prod.,2004,67(5):817-822.)从印尼海绵Leucetta chagosensis中首次分离得到了新的咪唑类生物碱Kealiinines A-C。在卤虫试验中,Kealiinine A表现出了较强的杀灭活性,在浓度为10μg/mL时其致死量就达到50%。最初分离鉴定的Kealiinines A-C的结构如下结构式一所示。
2012年,犹他大学Looper课题组(Org.Lett.,2012,14(18):4734-4737.)使用分子内亲电诱导的芳环与双键的环化以及氧化芳构化策略首次合成了报道的生物碱Kealiinine B和Kealiinine C(结构式二)。作者首先通过三组分炔丙胺化反应合成得到了中间体6和7,然后经四(三苯基膦)钯的催化作用下脱除N上的烯丙基得到中间体8和9,随后和Boc保护的甲硫基脒反应得到关键中间体10和11,然后反生分子内亲电诱导的芳环与双键的环化以及氧化芳构化反应经三氟乙酸脱Boc得到天然产物的三氟乙酸盐产物16和17。经过反复的核磁实验和谱图比较,确定所合成的化合物和天然分离得到的化合物是同一个化合物。同时他们还对这两个生物碱进行了对抗人体乳腺癌细胞的活性测试,发现Kealiinine B对乳腺癌细胞系有较好的抗有丝分裂活性,IC50值在10-13μM,而KealiinineC的抗有丝分裂活性则相对较弱,需要浓度在100μM以上才有一定活性。
同年,德州大学阿灵顿分校Lovely课题组(Org.Lett.2012,14(24):6210-6213.)也完成了Kealiinines A-C的全合成工作(结构式三)。他们从N-甲基-4,5-二碘咪唑出发,采用逐步修饰咪唑环然后通过傅克反应构筑芳环的策略合成了Kealiinines A-C。虽然合成的天然产物和分离得到的天然产物在核磁数据上有差别,但在液谱上的保留时间相同,作者认为是同一物质,核磁数据上的差别可能是由于化合物上氨基和亚胺的互变异构造成的,即化合物1与化合物Ia,化合物2与化合物Ib,化合物3与化合物Ic分别互为互变异构体。
2013年,Lovely课题组(Bioorg.Med.Chem.Lett.,2013,23(22):6183-6187.)报道了生物碱KealiininesA-C及其合成中间体的抗人体乳腺癌细胞MCF7活性(表1)。所有的天然生物碱都显示出较低的杀死癌细胞毒性,尤其是Kealiinine C。
表1抗人体乳腺癌细胞MCF7活性数据
2017年,鲁汶大学Van der Eycken课题组(Chem.Eur.J.2017,23,5224-5227.)发展了一例高加碘促进的炔丙基胍串联环化反应,他们使用与Looper课题组相同的中间体10和11,利用他们发展的方法顺利地合成了Kealiinine B和Kealiinine C生物碱(结构式四)。
到目前为止,虽然Kealiinine类生物碱具有较为成熟的合成路线,也被发现具有一定的抗癌活性和杀卤虫活性,但是它们的其他生物活性,尤其是在抗植物病毒和病菌中的活性还没有被系统的研究和报道,此外,它们的衍生物的生物活性也尚未被系统的研究。
发明内容
本发明提供Kealiinine类衍生物及其制备方法和在抗植物病毒和病菌中的应用。本专利的Kealiinine类衍生物具有很好的抗植物病毒和病菌活性。
本发明的Kealiinine类衍生物具有如下结构式五所示结构的化合物II,具体包括IIa,IIb,IIc,IId和IIe所示的化合物。
上式中IIa按照结构式六所示的方法制备:不同取代基的羧酸与Kealiinine B在HOBt和EDCI的缩合条件下,以二异丙基乙胺作碱,二氯甲烷作溶剂,室温反应得到IIa。
上式中IIb按照结构式七所示的方法制备:不同取代基的磺酰氯与Kealiinine B在吡啶做缚酸剂,二氯甲烷作溶剂,惰性气体保护的反应条件下反应得到IIb。
上式中IIc按照结构式八所示的方法制备:Kealiinine B与不同的取代基的醛缩合,用硼氢化钠还原得到IIc;
上式中IId按照结构式九所示的方法制备:以Kealiinine B为原料,羰基二咪唑作为酰基转移试剂,得到活性中间体31,不分离直接在反应体系中加入胺或醇的亲核试剂得到IId;
上式中IIe按照结构式十所示的方法制备:以中间体24b为原料,丁基锂拔去咪唑2位的氢,然后与不同的羰基化合物发生加成反应得到IIe;
以上通式及结构中:
R代表通式IIa,IIb,IIe,IId和IIe中所示的取代基,氰基,H;
在通式IIa中R1代表:1-9个碳的直链烷基,1-9个碳支链烷基,1-9个碳环烷基,1-9个碳碳链上含有其它取代基(包括氨基、酯基、氰基、酰胺基、含硫含氧取代基、苯基、杂芳基)的烷基,具有取代基的苯基,具有取代基的杂芳基;
在通式IIb中R2代表:具有取代基的苯基,具有取代基的杂芳基,1-9个碳的烷基;
在通式IIe中R3代表:具有取代基的苯基,具有取代基的杂芳基;
在通式IId中X和R4代表以下几种情况:
X代表氧原子,R4代表1-9个碳的直链烷基,1-9个碳支链烷基,1-9个碳环烷基,具有取代基的苯甲基,具有取代基的杂芳甲基,具有取代基的苯基,具有取代基的杂芳基;
X代表NH,R4代表代1-9个碳的直链烷基,1-9个碳支链烷基,1-9个碳环烷基,具有取代基的苯甲基,具有取代基的杂芳甲基,具有取代基的苯基,具有取代基的杂芳基;
X代表N-R4′,R4代表1-9个碳的直链烷基,1-9个碳支链烷基,1-9个碳环烷基,具有取代基的苯甲基,具有取代基的杂芳甲基,具有取代基的苯基,具有取代基的杂芳基,R4’代表1-9个碳的直链烷基,1-9个碳支链烷基,1-9个碳环烷基,具有取代基的苯甲基,具有取代基的杂芳甲基,具有取代基的苯基,具有取代基的杂芳基;
X代表N-R4′,R4与R4’相连成环状结构含氮杂环(包括吗啉环,哌啶环,哌嗪环,咪唑环);
在通式IIe中R5代表H,1-9个碳的直链烷基,1-9个碳支链烷基,1-9个碳环烷基,具有取代基的苯甲基,具有取代基的杂芳甲基,具有取代基的苯基,具有取代基的杂芳基,R6代表H,1-9个碳的直链烷基,1-9个碳支链烷基,1-9个碳环烷基,具有取代基的苯甲基,具有取代基的杂芳甲基,具有取代基的苯基,具有取代基的杂芳基。
本发明优选化合物如结构式十一所示II-1~II-12。
本发明的Kealiinine类衍生物II表现出很好的抗植物病毒和病菌活性,能很好地抑制烟草花叶病毒(TMV)和黄瓜枯萎,花生褐斑,苹果轮纹,小麦纹枯,玉米小斑,西瓜炭疽,水稻恶苗,番茄早疫,小麦赤霉,马铃薯晚疫,辣椒疫霉,油菜菌核,黄瓜灰霉,水稻纹枯14种植物病菌。
具体实施方式
下述的实施例和生测试验结果可用来进一步说明本发明,但不意味着限制本发明。
实施例1:Kealiinine类衍生物II-1的合成
在一个100mL的圆底烧瓶中加入EDCI(0.19g,1.00mmol),HOBt(22mg,0.16mmol),环戊基甲酸(95mg,0.83mmol)和DIPEA(0.32g,2.49mmol),用30mL重蒸的二氯甲烷溶解,室温搅拌30min,加入Kealiinine B(0.30g,0.83mmol),氩气保护,室温搅拌10h,TLC监测。加30mL水稀释反应液,分液,水相用二氯甲烷萃取(30mL×3),合并有机层,饱和食盐水洗,无水硫酸钠干燥,抽滤,减压脱溶,柱层析(V(石油醚)∶V(乙酸乙酯)=6∶1→V(石油醚)∶V(乙酸乙酯)=4∶1→V(石油醚)∶V(乙酸乙酯)=3∶1),淡黄色固体,收率62%,熔点196-197℃。1H NMR(400MHz,CDCl3)δ11.71(s,1H),7.42(d,J=8.8Hz,2H),7.41(s,1H),7.21(s,1H),7.14(s,1H),7.10(d,J=8.8Hz,2H),4.02(s,3H),3.91(s,3H),3.81(s,3H),3.71(s,3H),3.01-2.87(m,1H),2.01-1.90(m,2H),1.90-1.80(m,2H),1.79-1.67(m,2H),1.79-1.67(m,2H).13C NMR(100MHz,CDCl3)δ189.0,159.6,154.4,148.8,148.7,130.9,129.0,126.9,126.6,126.0,124.6,119.3,115.0,106.1,104.1,103.1,55.9,55.7,55.4,49.6,31.0,28.4,26.2.HR-MS(ESI):Calcd for C27H30N3O4[M+H]+460.2231,found(ESI+)460.2234.
实施例2:Kealiinine类衍生物II-2的合成
在一个100mL的圆底烧瓶中加入Kealiinine B(0.20g,0.55mmol),DMAP(0.013g,0.11mmol),三乙胺(0.067g,0.66mmol),用20mL二氯甲烷溶解,氩气保护,向其中缓慢滴加甲烷磺酰氯(0.13g,1.13mmol)的二氯甲烷(2mL)溶液,滴加完毕,室温搅拌1h,TLC监测。加20mL水将反应淬灭,分液,水相用二氯甲烷萃取(60mL×3),合并有机层,饱和食盐水洗,无水硫酸钠干燥,抽滤,减压脱溶,粗品柱层析(V(二氯甲烷)∶V(甲醇)=50∶1),得淡黄色固体0.21g,收率86%,熔点204-205℃。1H NMR(400MHz,CDCl3)δ9.76(s,1H),7.39(d,J=8.4Hz,2H),7.35(s,1H),7.21(s,1H),7.12(s,1H),7.11(d,J=8.4Hz,2H),4.02(s,3H),3.91(s,3H),3.81(s,3H),3.58(s,3H),3.05(s,3H).13C NMR(100MHz,CDCl3)δ159.7,151.0,148.9,148.8,130.8,129.0,126.5,126.4,125.5,124.6,118.9,115.1,106.3,104.1,103.2,55.9,55.7,55.4,42.7,28.3.HR-MS(ESI):Calcd for C22H24N3O5S[M+H]+442.1431,found(ESI+)442.1429.
实施例3:Kealiinine类衍生物II-3和II-4的合成
II-3:在一个100mL的圆底烧瓶中加入Kealiinine B(0.52g,1.43mmol),苯甲醛(0.23g,2.17mmol),甲苯(30mL),升温至110℃,反应过夜。减压脱溶,除去甲苯,加入乙醇(30mL),室温搅拌下分批加入硼氢化钠(0.20g,5.26mmol),反应3h,TLC监测。加少量水将反应淬灭,减压脱除大部分溶剂,加50mL水,用二氯甲烷萃取(80mL×3),合并有机层,饱和食盐水洗,无水硫酸钠干燥,抽滤,减压脱溶,粗品柱层析(V(二氯甲烷)∶V(甲醇)=50∶1),得黄色固体0.49g,收率76%,熔点112-114℃。1H NMR(400MHz,CDCl3)δ7.57(d,J=8.4Hz,2H),7.30-7.22(m,6H),7.21(s,1H),7.18(s,1H),7.00(d,J=8.4Hz,2H),4.74(s,1H),4.51(s,2H),3.99(s,3H),3.79(s,3H),3.75(s,3H),3.35(s,3H).13C NMR(100MHz,CDCl3)δ158.4,156.0,147.5,147.3,140.1,138.9,135.4,132.4,129.9,128.5,128.3,127.5,125.0,124.1,123.1,113.5,106.1,104.7,100.9,55.8,55.6,55.2,47.5,28.3.HR-MS(ESI):Calcdfor C28H28N3O3[M+H]+454.2125,found(ESI+)454.2119.
化合物II-4的合成参照化合物II-3的合成方法,原料为相应原料。
II-4:柱层析(V(二氯甲烷)∶V(甲醇)=50∶1→V(二氯甲烷)∶V(甲醇)=20∶1),淡黄色固体,收率46%,熔点139-140℃。1H NMR(400MHz,CDCl3)δ8.54(d,J=4.4Hz,1H),7.67(td,J=7.6,1.6Hz,1H),7.60(d,J=7.6Hz,2H),7.36(d,J=8.8Hz,1H),7.28(s,1H),7.27(s,1H),7.24-7.21(m,1H),7.20(s,1H),7.10(d,J=8.8Hz,2H),6.10(s,1H),4.79(s,2H),4.01(s,3H),3.92(s,3H),3.82(s,3H),3.64(s,3H).13C NMR(100MHz,CDCl3)δ158.5,156.9,155.9,148.7,147.5,147.3,136.6,135.3,132.4,129.9,125.0,124.0,122.8,122.7,122.4,113.6,106.1,104.7,101.0,55.8,55.6,55.3,47.7,28.5.HR-MS(ESI):Calcd forC27H27N4O3[M+H]+455.2078,found(ESI+)455.2069.
实施例4:Kealiinine类衍生物II-5~II-9的合成
II-5:在一个100mL的圆底烧瓶中加入N,N’-羰基二咪唑(0.15g,0.93mmol),无水四氢呋喃(30mL),搅拌下加入Kealiinine B(0.25g,0.69mmol),升温至50℃反应4h,TLC监测。将反应液减压脱溶,柱层析(V(石油醚)∶V(乙酸乙酯)=1∶2→V(二氯甲烷)∶V(甲醇)=100∶1),得淡黄色固体0.28g,收率89%,熔点280-281℃。1H NMR(400MHz,CDCl3)δ11.03(s,1H),8.41(s,1H),7.63(s,1H),7.48(s,1H),7.45(d,J=8.4Hz,2H),7.24(s,1H),7.16(s,1H),7.15(d,J=8.4Hz,2H),7.05(s,1H),4.04(s,3H),3.94(s,3H),3.82(s,3H),3.77(s,3H).13C NMR(100MHz,CDCl3)δ159.8,156.9,154.9,149.2,149.1,137.4,130.9,129.7,128.8,126.9,126.5,125.5,125.0,119.7,117.1,115.1,106.2,104.0,103.7,55.9,55.8,55.4,28.4.
II-6:在一个100mL的圆底烧瓶中加入中间体II-5(0.20g,0.43mmol),无水四氢呋喃(20mL),搅拌下加入丙胺(0.03g,0.51mmol),室温反应6h,TLC监测。减压脱溶,粗品柱层析(V(二氯甲烷)∶V(甲醇)=100∶1),得白色固体0.18g,收率92%,熔点291-292℃。1H NMR(400MHz,CDCl3)δ11.10(s,1H),7.42(d,J=8.0Hz,2H),7.26(s,1H),7.19(s,1H),7.10(s,1H),7.09(d,J=8.0Hz,2H),5.28-5.21(m,1H),4.01(s,3H),3.91(s,3H),3.80(s,3H),3.55(s,3H),3.24-3.16(m,2H),1.62-1.47(m,2H),0.94(t,J=8.0Hz,3H).13C NMR(100MHz,CDCl3)δ164.8,159.4,154.6,148.4,148.3,131.0,129.8,127.2,126.6,126.1,124.3,118.0,115.0,106.2,104.3,102.2,55.9,55.7,55.3,42.1,27.8,23.4,11.5.HR-MS(ESI):Calcd for C25H29N4O4[M+H]+449.2183found(ESI+)449.2189.
化合物II-7的合成参照化合物II-6的合成方法,原料为相应原料。
II-7:柱层析(200-300目硅胶,V(二氯甲烷)∶V(甲醇)=200∶1→V(二氯甲烷)∶V(甲醇)=100∶1→V(二氯甲烷)∶V(甲醇)=50∶1),淡黄色固体,收率58%,熔点245-246℃。1H NMR(400MHz,CDCl3)δ11.17(s,1H),7.43(d,J=8.8Hz,2H),7.30(s,1H),7.20(s,1H),7.13(s,1H),7.10(d,J=8.8Hz,2H),4.02(s,3H),3.91(s,3H),3.91-3.83(m,2H),3.81(s,3H),3.74-3.66(m,4H),3.60(s,3H),3.65-3.48(m,2H).13C NMR(100MHz,CDCl3)δ163.3,159.4,154.8,148.5,148.36,131.0,129.7,127.2,126.5,126.1,124.2,118.2,114.9,106.2,104.1,102.3,67.1,55.9,55.7,55.4,27.9.HR-MS(ESI):Calcd for C26H29N4O5[M+H]+477.2132,found(ESI+)477.2140.
II-8:在一个100mL的圆底烧瓶中加入Kealiinine B(0.23g,0.63mmol),无水四氢呋喃(30mL),搅拌下加入N,N’-羰基二咪唑(0.11g,0.68mmol),室温反应1h,TLC监测。Kealiinine B反应完全后,加入二异丙基胺(58mg,0.76mmol),室温反应6h,TLC监测。将反应液旋干,加入少量甲醇,超声,抽滤,得淡黄色固体,收率50%,熔点286-288℃。1H NMR(400MHz,CDCl3)δ11.08(s,1H),7.41(d,J=8.4Hz,2H),7.25(s,1H),7.19(s,1H),7.09(s,1H),7.08(d,J=8.4Hz,2H),4.39(s,1H),4.01(s,1H),4.01(s,3H),3.91(s,3H),3.79(s,3H),3.60(s,3H),1.41(d,J=4.0Hz,6H),1.21(d,J=4.0Hz,6H).13C NMR(100MHz,CDCl3)δ163.4,159.4,154.0,148.3,148.1,131.1,130.2,127.4,127.0,126.0,124.2,117.8,114.9,106.2,104.3,101.7,55.9,55.7,55.3,45.4,45.0,27.9,21.9,20.8.HR-MS(ESI):Calcd for C28H35N4O4[M+H]+491.2653,found(ESI+)491.2656.
化合物II-9的合成参照化合物II-8的合成方法,原料为相应原料。
II-9:黄色固体,收率90%,熔点127-129℃。1H NMR(400MHz,CDCl3)δ10.87(s,1H),7.53(d,J=8.8Hz,2H),7.48(s,1H),7.32(s,1H),7.24(s,1H),7.23(d,J=8.8Hz,2H),4.13(s,3H),4.03(s,3H),3.92(s,3H),3.86(s,3H),3.76(s,3H).13C NMR(100MHz,CDCl3)δ164.4,159.6,155.7,148.8,148.7,130.9,129.4,126.8,126.5,125.8,124.5,118.8,115.0,106.2,104.1,103.0,55.8,55.7,55.3,52.5,28.1.HR-MS(ESI):Calcd forC23H24N3O5[M+H]+422.1710,found(ESI+)422.1712.
实施例5:Kealiinine类衍生物II-10~II-12的合成
II-10:在一个烘干的100mL圆底烧瓶中加入中间体24b(0.40g,1.15mmol),无水四氢呋喃(20mL),氩气保护,冷却至-78℃,注射正丁基锂(0.9mL,1.6M in hexane),保持该温度反应3h,再注射环戊酮(120mg,1.43mmol),保持该温度反应过夜,TLC监测。加饱和氯化铵溶液将反应淬灭,水相用乙酸乙酯萃取(20mL×3),合并有机层,饱和食盐水洗涤,无水硫酸钠干燥,抽滤,减压脱溶。柱层析(V(石油醚)∶V(乙酸乙酯)=6∶1→V(石油醚)∶V(乙酸乙酯)=4∶1→V(石油醚)∶V(乙酸乙酯)=2∶1),淡黄色固体,收率30%,熔点191-192℃。1H NMR(400MHz,CDCl3)δ7.63(d,J=8.4Hz,2H),7.52(s,1H),7.36(s,1H),7.21(s,1H),7.09(d,J=8.4Hz,2H),4.03(s,3H),3.93(s,3H),3.91(s,3H),3.84(s,3H),3.50(s,1H),2.45-2.31(m,2H),2.18-2.06(m,2H),2.06-1.92(m,2H),1.89-1.74(m,2H).13C NMR(100MHz,CDCl3)δ159.9,158.7,148.6,147.8,138.6,136.9,132.6,129.1,127.1,127.0,123.9,113.6,105.7,104.5,102.8,80.2,55.8,55.6,55.3,40.2,31.4,24.6.HR-MS(ESI):Calcd forC26H29N2O4[M+H]+433.2127,found(ESI+)433.2127.
化合物II-11和II-12的合成参照化合物II-10的合成方法,原料为相应原料。
II-11:柱层析(200-300目硅胶,V(石油醚)∶V(乙酸乙酯)=6∶1→V(石油醚)∶V(乙酸乙酯)=4∶1),淡黄色固体,收率59%,熔点218-219℃。1H NMR(400MHz,CDCl3)δ7.70(d,J=8.8Hz,2H),7.45(s,1H),7.41(s,1H),7.39-7.24(m,5H),7.19(s,1H),7.12(d,J=8.8Hz,2H),4.50(s,1H),4.01(s,3H),3.93(s,3H),3.85(s,3H),3.39(s,3H),2.05(s,3H).13C NMR(100MHz,CDCl3)δ160.2,158.8,148.8,148.0,143.8,138.3,136.8,132.6,129.1,128.6,127.8,127.4,127.2,125.7,124.0,113.7,105.7,104.5,103.0,73.2,55.8,55.7,55.3,31.0,29.0.HR-MS(ESI):Calcd for C29H29N2O4[M+H]+469.2122,found(ESI+)469.2118.
II-12:柱层析(V(石油醚)∶V(乙酸乙酯)=6∶1→V(石油醚)∶V(乙酸乙酯)=4∶1),黄色固体,收率49%,熔点82-84℃。1H NMR(400MHz,CDCl3)δ7.64(d,J=8.0Hz,2H),7.55(s,1H),7.40(s,1H),7.24(s,1H),7.10(d,J=8.0Hz,2H),4.78(s,1H),4.03(s,3H),3.92(s,6H),3.85(s,3H),2.05-1.90(m,2H),1.68(s,3H),1.53-1.37(m,1H),1.34-1.18(m,2H),1.06-0.92(m,1H),0.83(t,J=7.2Hz,3H).13C NMR(100MHz,CDCl3)δ161.0,158.8,148.7,148.0,137.9,137.0,132.6,129.0,127.0,124.0,113.6,105.7,104.5,102.9,72.0,55.8,55.7,55.3,40.9,31.6,27.8,25.9,22.8,14.0.HR-MS(ESI):Calcd for C27H33N2O4[M+H]+449.2435,found(ESI+)449.2425.
实施例6:抗烟草花叶病毒活性的测定,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l×105μg/mL母液,后用含1‰吐温80水溶液稀释至所需浓度;宁南霉素制剂直接兑水稀释。
3、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。
4、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。
5、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2 Kealiinine类衍生物II-1~II-12的抗烟草花叶病毒(TMV)活性测试结果:
从表2中可见Kealiinine类衍生物II-1~II-12表现出很好的抗烟草花叶病毒活性,其中化合物II-5、II-10、II-11和II-12的抗TMV活性非常好,远超过了病毒唑,甚至和宁南霉素相当,具备极大的开发价值。
实施例5:抗菌活性测试,测定程序如下:
离体杀菌测试,菌体生长速率测定法(平皿法):
将一定量药剂溶解在适量丙酮内,然后用含有200ug/mL乳化剂水溶液稀释至所需浓度,然后各吸取1mL药液注入培养皿内,再分别加入9mL培养基,摇匀后制成50ug/mL的含药平板,以添加1mL灭菌水的平板做空白对照。用直径4mm的打孔器沿菌丝外缘切取菌盘,移至含药平板上。每处理重复三次。将培养皿放在24+1℃恒温培养箱内培养。48小时后调查各处理菌盘扩展直径,求平均值,与空白对照比较计算相对抑菌率。
表3 Kealiinine类衍生物II-1~II-12的抗植物病菌活性测试结果:
从表3中可以看出,Kealiinine类衍生物II-1~II-12表现出一定的抗植物病菌活性,化合物II-3在50mg/kg的浓度下对油菜菌核的抑制率超过了70%,化合物II-7在50mg/kg的浓度下对小麦纹枯的抑制率超过了70%。
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