新型含氮杂环活性化合物的合成及活性研究
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摘要
含氮杂环化合物不管在农药中还是在医药中,都有很好的效果。长期以来,一直是人们研究的热点。为了探寻新的含氮杂环农药，我们合成了部分新型含氮杂环活性化合物、对其结构进行了表征并测定了它们的生物活性。
第一部分采用简便的“一锅煮法”合成了12个含氮杂环的硫脲类化合物，其中10个化合物属首次报道的新化合物，其结构通过元素分析、IR、1H NMR及MS得到确证。采用琼脂稀释法以甲基托布津为对照药剂用苹果轮纹病菌对该12个化合物做了室内毒力试验，除了2个化合物对病原菌有促生作用以外，其余化合物对苹果轮纹病菌均有抑制作用，其EC50在4.94～16.14mg/g之间。其中5个化合物的EC95均不超过对照药剂，有3个化合物的EC95还远远低于对照药剂。选取4个活性较好的化合物用10个病原菌作杀菌谱，供试的菌种涉及到的作物有粮食类、经济类、瓜果类和蔬菜等极为重要的农作物。供试药剂对大多数供试病菌的EC50 ＜30mg/g，最高的为80.31mg/g，最低者只有6.92mg/g 。这说明，这一类化合物对大多数病菌都具有一定效果，具有一定的广谱性。特别是化合物(Ⅰb)，对所有病原菌的EC50均在20mg/g左右，EC95也大都在50～60mg/g之间，只有对苹果黑星病菌 (Venturia inaequalis)和番茄灰腐病菌(BotrYtis cinerea)分别为160.49、167.98mg/g。
第二部分中，选取本身具有杀虫活性的基团取代吡虫清中的2-氯-5-氯甲基吡啶，采用“类同合成法”合成了3个烟碱类杀虫剂吡虫清的类似物。该3个化合物均为首次报道的新化合物。其结构通过元素分析、IR、1H NMR及MS得到确证。
Nitrogen-containing heterocyclic compounds have a good activity not only in pesticide but also in medicine. They have been researched for a long time. In order to find novel nitrogen heteocyclic pesticide, some compounds were synthesized, their structures were characterized and their biology activities were tested.
Part one, twelve compounds were synthesized by "one-pot method", ten of which are firstly reported, the structures of them were confirmed by elemental analysis、IR、 MS、and 1H NMR spectrometry. The toxicity of these twelve compounds to Macrophoma kawatsukai was tested with Methyl-Thiophanate as check in laboratory through agar dilution method. The results showed that the compounds have an inhibiting effect on Macrophoma kawatsukai except that two compounds have a growth promotion effect, the EC50 of which is between 4.94~16.14mg/g. The EC95 of five compounds is less than that of Methyl-Thiophanate. Four better active compounds were selected to make fungicide spectrum, using ten pathogenic bacterium which related to many important crops、grains、fruits and vegetables. The EC50 of four compounds to most of pathogenic bacterium is less 30mg/g, the highest value is 80.31mg/g, the least value is 6.92mg/g, which showed these kinds of compounds had some effect on most of pathogenic bacterium and had some broad spectrum quality. Especially, the EC50 of compound (Ⅰb) to all of pathogenic bacterium is about 20mg/g, the EC95 of that is between 50~60mg/g except that the EC95 of that to Venturia inaequalis and Botrytis cinerea are 160.49mg/g and 167.98mg/g.
Part two, Three analogue compounds of actamiprid were synthesized by analogue synthesis method through the intermediates which have insecticide activity. The compounds are firstly reported, the structures of which were confirmed by elemental analysis、IR、1H NMR and MS spectrometry.
第一部分采用简便的“一锅煮法”合成了12个含氮杂环的硫脲类化合物，其中10个化合物属首次报道的新化合物，其结构通过元素分析、IR、1H NMR及MS得到确证。采用琼脂稀释法以甲基托布津为对照药剂用苹果轮纹病菌对该12个化合物做了室内毒力试验，除了2个化合物对病原菌有促生作用以外，其余化合物对苹果轮纹病菌均有抑制作用，其EC50在4.94～16.14mg/g之间。其中5个化合物的EC95均不超过对照药剂，有3个化合物的EC95还远远低于对照药剂。选取4个活性较好的化合物用10个病原菌作杀菌谱，供试的菌种涉及到的作物有粮食类、经济类、瓜果类和蔬菜等极为重要的农作物。供试药剂对大多数供试病菌的EC50 ＜30mg/g，最高的为80.31mg/g，最低者只有6.92mg/g 。这说明，这一类化合物对大多数病菌都具有一定效果，具有一定的广谱性。特别是化合物(Ⅰb)，对所有病原菌的EC50均在20mg/g左右，EC95也大都在50～60mg/g之间，只有对苹果黑星病菌 (Venturia inaequalis)和番茄灰腐病菌(BotrYtis cinerea)分别为160.49、167.98mg/g。
第二部分中，选取本身具有杀虫活性的基团取代吡虫清中的2-氯-5-氯甲基吡啶，采用“类同合成法”合成了3个烟碱类杀虫剂吡虫清的类似物。该3个化合物均为首次报道的新化合物。其结构通过元素分析、IR、1H NMR及MS得到确证。
Nitrogen-containing heterocyclic compounds have a good activity not only in pesticide but also in medicine. They have been researched for a long time. In order to find novel nitrogen heteocyclic pesticide, some compounds were synthesized, their structures were characterized and their biology activities were tested.
Part one, twelve compounds were synthesized by "one-pot method", ten of which are firstly reported, the structures of them were confirmed by elemental analysis、IR、 MS、and 1H NMR spectrometry. The toxicity of these twelve compounds to Macrophoma kawatsukai was tested with Methyl-Thiophanate as check in laboratory through agar dilution method. The results showed that the compounds have an inhibiting effect on Macrophoma kawatsukai except that two compounds have a growth promotion effect, the EC50 of which is between 4.94~16.14mg/g. The EC95 of five compounds is less than that of Methyl-Thiophanate. Four better active compounds were selected to make fungicide spectrum, using ten pathogenic bacterium which related to many important crops、grains、fruits and vegetables. The EC50 of four compounds to most of pathogenic bacterium is less 30mg/g, the highest value is 80.31mg/g, the least value is 6.92mg/g, which showed these kinds of compounds had some effect on most of pathogenic bacterium and had some broad spectrum quality. Especially, the EC50 of compound (Ⅰb) to all of pathogenic bacterium is about 20mg/g, the EC95 of that is between 50~60mg/g except that the EC95 of that to Venturia inaequalis and Botrytis cinerea are 160.49mg/g and 167.98mg/g.
Part two, Three analogue compounds of actamiprid were synthesized by analogue synthesis method through the intermediates which have insecticide activity. The compounds are firstly reported, the structures of which were confirmed by elemental analysis、IR、1H NMR and MS spectrometry.
引文
参考文献
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1、唐除痴,李煜昶,陈 彬等.《农药化学》天津:南开大学出版社,1998:3.
2、张一宾,张 怿.《农药》北京:中国物资出版社，1997:7.
3、唐除痴,李煜昶,陈 彬等.《农药化学》天津:南开大学出版社,1998:5.
4、张一宾,张 怿.《农药》北京:中国物资出版社，1997:15.
5、钱旭红.《简明农药化学-农用生物化学调控导论》上海:华东理工大学出版社,1994:2～7.
6、鲁明中,陈年春.《农药生态学》,北京:中国环境科学出版社,1993:46～64.
7、杨小平.《守卫绿色-农药与人类的生存》湖南:湖南教育出版社,1999:92～94.
8、李宗成.国外农药研究动向,农药,1998,37(1):1～3.
9、郭予元.我国农作物有害生物发生和防治研究概况,农药, 1998,37(12):1～3.
10、罗乃春,慕立义.杀虫剂现状及发展前景,农药,1997,36(6):12.
11、胡笑形.我国农药工业的现状与发展方向,农药,1998,37(6):7～10
12、鲁明中,陈年春.《农药生态学》,北京:中国环境科学出版社,1993:264.
13、程万义,薛振祥,王能武.《新农药研究与开发》北京:化学工业出版社,1996:4.
14、刘长令.美国农药新法规,农药译丛,1997,19(1):63.
15、钱跃言.新政策与农药,农药译丛,1998,20(6):50～55.
16、张一宾.对中国农药发展之浅见,农药,1998,37(5):1～2.
17、柏再苏,王大翔.杂环、基因工程和二十一世纪的农药, 农药,1998,37(6):2～6.