广谱尘螨抑制剂的制备以及抗尘螨效果的研究
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摘要
由于室内尘螨经常在居家各场所发生，且是多种过敏症的诱发因子，因此，对于尘螨的防治受到了世界各国研究人员的广泛关注。
拟除虫菊酯是一种高效低毒的杀螨剂，近年来，拟除虫菊酯杀螨剂的热稳定性和耐气候稳定性都比较好，应该说，如果能够有效的降低其对哺乳动物的毒性的话，拟除虫菊酯是一种能够比较适合作为织物抗尘螨整理剂中有效成分的杀螨剂。
通过对已有的拟除虫菊酯类化合物的结构分析，我们设计合成了一系列新的高效、低毒、稳定的N-芳基缬氨酸类拟除虫菊酯杀螨剂，并对其进行了生物活性测试。
合成方法主要按照以下两条路线进行：
1．从基本原料异戊酸出发，经过酰氯化、溴代、酯化和胺化反应而制得相应的N-芳基缬氨酸酯。
2．从基本原料异戊酸出发，经过溴代(HVZ反应)、胺化和酯化反应而制得相应的N-芳基缬氨酸酯。
两条路线中关键的一步反应是芳胺和溴代化合物的亲核取代反应，一般这步反应产率很低，并且需要较长的反应时间。为了提高该反应产率，我们讨论了选择不同的溶剂对该反应收率产生的影响，同时加入了少量的催化剂；为了缩短反应时间，我们初步尝试了将超声波技术引入了该反应，并取得了较好的效果。
拟除虫菊酯的生物活性表现是多方面的，其中对杀虫杀螨效果而言最先考虑的是致死作用，本论文通过测定粉尘螨的致死中浓度LC_(50)来分析待测物的致死作用，结果表明我们所制备的新的化合物对供试品种粉尘螨都是有效的，其中部分化合物的效果显著。
Because the indoor dust and mite often disappears in the each place of daily life at home and it is the factor of various allergies, so that, the prevention and cure of dust and mite is suffered the extensive concern of the international community researcher.
Pyrethroid is a kind of insecticide of efficiently killing and low poison, in recent years, the stability of bearing the hot and the weather of pyrethroid is all good, so pyrethroid can be fit to be used as the anti-dust and mite finishing agent on the fabric if it can be efficiently knocked-down the toxicity for mammals.
Through the structure analysis of the known pyrethroid, we designed and synthesized a new series of pyrethroid-N-aryl valine series pyrethroid insecticides, and proceeded the living creature activity test for them.
The synthetic methods are as follows:
1. The compounds were prepared by using isovaleric acid as starting material through acyl chlorination,bromination, esterification and animation in overall four steps.
2. We prepared the compounds using isovaleric acid as starting material through brominaton(HVZ reaction),amination and esterification in an overall three steps.
The key step of the two routes is the reaction of nucleophilic substitution of aromatic amines and -bromo compounds. Generally the produce rate of this reaction is low and the reaction time is long. In order to improve the produce rate, we studied the effect of choosing the different solvents on the produce rate of the reaction of nucleophilic substitution, and we added a litttle catalyzer at the same time; in order to shorten the reaction time, we tried to put the supersonic wave on the yield of the
reaction, and we got the better effect.
The living creature activity of pyrethroid is various, thereof the lethal effect is the first consideration in regard to the result of killing dust and mite. We analyzed the lethal effect of the compounds by determining the median lethal concentration LC50 of power dust, and the result showed that the prepared compounds were effective for power and dust, thereof some compounds had the prominent effect.
拟除虫菊酯是一种高效低毒的杀螨剂，近年来，拟除虫菊酯杀螨剂的热稳定性和耐气候稳定性都比较好，应该说，如果能够有效的降低其对哺乳动物的毒性的话，拟除虫菊酯是一种能够比较适合作为织物抗尘螨整理剂中有效成分的杀螨剂。
通过对已有的拟除虫菊酯类化合物的结构分析，我们设计合成了一系列新的高效、低毒、稳定的N-芳基缬氨酸类拟除虫菊酯杀螨剂，并对其进行了生物活性测试。
合成方法主要按照以下两条路线进行：
1．从基本原料异戊酸出发，经过酰氯化、溴代、酯化和胺化反应而制得相应的N-芳基缬氨酸酯。
2．从基本原料异戊酸出发，经过溴代(HVZ反应)、胺化和酯化反应而制得相应的N-芳基缬氨酸酯。
两条路线中关键的一步反应是芳胺和溴代化合物的亲核取代反应，一般这步反应产率很低，并且需要较长的反应时间。为了提高该反应产率，我们讨论了选择不同的溶剂对该反应收率产生的影响，同时加入了少量的催化剂；为了缩短反应时间，我们初步尝试了将超声波技术引入了该反应，并取得了较好的效果。
拟除虫菊酯的生物活性表现是多方面的，其中对杀虫杀螨效果而言最先考虑的是致死作用，本论文通过测定粉尘螨的致死中浓度LC_(50)来分析待测物的致死作用，结果表明我们所制备的新的化合物对供试品种粉尘螨都是有效的，其中部分化合物的效果显著。
Because the indoor dust and mite often disappears in the each place of daily life at home and it is the factor of various allergies, so that, the prevention and cure of dust and mite is suffered the extensive concern of the international community researcher.
Pyrethroid is a kind of insecticide of efficiently killing and low poison, in recent years, the stability of bearing the hot and the weather of pyrethroid is all good, so pyrethroid can be fit to be used as the anti-dust and mite finishing agent on the fabric if it can be efficiently knocked-down the toxicity for mammals.
Through the structure analysis of the known pyrethroid, we designed and synthesized a new series of pyrethroid-N-aryl valine series pyrethroid insecticides, and proceeded the living creature activity test for them.
The synthetic methods are as follows:
1. The compounds were prepared by using isovaleric acid as starting material through acyl chlorination,bromination, esterification and animation in overall four steps.
2. We prepared the compounds using isovaleric acid as starting material through brominaton(HVZ reaction),amination and esterification in an overall three steps.
The key step of the two routes is the reaction of nucleophilic substitution of aromatic amines and -bromo compounds. Generally the produce rate of this reaction is low and the reaction time is long. In order to improve the produce rate, we studied the effect of choosing the different solvents on the produce rate of the reaction of nucleophilic substitution, and we added a litttle catalyzer at the same time; in order to shorten the reaction time, we tried to put the supersonic wave on the yield of the
reaction, and we got the better effect.
The living creature activity of pyrethroid is various, thereof the lethal effect is the first consideration in regard to the result of killing dust and mite. We analyzed the lethal effect of the compounds by determining the median lethal concentration LC50 of power dust, and the result showed that the prepared compounds were effective for power and dust, thereof some compounds had the prominent effect.
引文
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[2] E. Tovey, Nature, 289, 529(1981)
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[27] Gaynor IR T., Hughes J. F., Medical & Biological Engineering & Computing Vol. 36, No.5,615-620(1998)
[28] Harvilicz, Helena, Chemical Market Reporter Vol.255 No.2 (Jan. 11 999) p.20
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[30] Kniest F. M. et al., Journal of Aerosol Science, Vol.23, No. suppl. 1, S551-S554(1992)
[31] Anon, Textile-Industries-Dyegest-Southem-Africa, 14(10), 5(1995)
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[33] Gore-and-Associates-(UK)-Ltd-WL., Medical-Textiles, November, 5-6(1993)
[34] Brzezinski-S et al., Fibers-and-Textiles-in-Eastem-Europe, 4(3-4), 124-125 (1996)
[35] Teijin Ltd., Medical-Textiles, January, 2(1997)
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[37] Kniest, F.M., Journal of Aerosol Science, Vol.22, No. suppl. 1, S827-S830(1991)
[38] Bossard et al., International Textile Bulletin, Dyeing/Printing/Finishing(English Edition) Vol.41 4th Quarter 3(1995)
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[40] Bossard, Mel liand-Textiberichte, E195, 735-736(1999)
[41] Bossard, International-Carpet-Yearbook, 2000, 22-24(2000)
[42] Carlier-F, Industrial Textile, 1270(11), 67-68(1995)
[43] Technisehe-Textilien, 2000, 43(1): E3
[44] Gacen-J, Revista-de-la-Industria-Textil, 373, 41-45(1999)
[45] High-Performance-Textiles, Nov., 2(1999)
[46] Schobesberger-CP, Asian Textile Journal, 8(4), 127-130(1999)
[47] International Dyer, 184(2), 38-39(1999)
[48] Lewis, R.D. American Industrial Hygiene Association Journal p.606-613(1998)
[49] 刘长令，农药科学与管理，1998年第2期，p28
[50] Mitsubishi Chemical Industries Limited Technical "Bulletin Pyrethroid Insecticide: MAVRIK" (1984)
[51] Georghiou, George P. et al., The occurrence of resistance to pesticides in arthropods, Food and Agriculture Organization of the United Nations, 1991 Doc.
[52] 见里朝下(日本理化学研究所微生物药理研究室主任)，新农药的开发，1984年8月在上海农药所所作的学术报告
[53] Y. Katsuda et al., JP 156,335(1975)
[54] C. A. Henrick et al., Pestic. Sci., 11,224(1980)
[55] 熊怀棱丸，有机合成化学学会志，42，786 (1980)
[56] CA. Henrick etal., Pestic Sci., 11,224(1980)
[57] 吉冈宏辅，有机合成化学学会志，42(9)，809(1984)
[58] 顾可权等，华东师范大学学报No．4,73(1981)
[59] Elliott M. et al., Nature, 246, 169(1973)
[60] U.S.P. 4,243,819
[61] JP78-121731
[62] U.S.P. 4,260.633
[63] U.S.P. 4,226,802
[64] 李达文等，实用有机化学手册，399(1981)
[65] 顾可权，拟除虫菊酯，82(1984)
[66] Org. Syn., Coll., Vol.4, 792(1963)
[67] E.von Bisehoff et al., Allergologie, 9, 45(1986)
[68] E.Petri et al., Allerologie, 5, 109(1982)
[2] E. Tovey, Nature, 289, 529(1981)
[3] E. Tovey et al., Allergologie, 5, 109(1982)
[4] Swanson M.C., et al., J. Allergy Clin. Immunol. 83,776-783 (1989)
[5] 泰兴国等，国外医学卫生学分册，Vol．24，No．5，286(1997)
[6] de Blay et al., Allergy Clin. Immunol., 93, 136-138(1994)
[7] J. Van Bronswi jk, "house Dust Biology", NIB Publishers, Zeist, 1981
[8] Platts Mill et～L., Belgian Journal of Zoology, Vol. 125, No. 1,193 (1995)
[9] 蔡黎等，生态学报，9(3)，128(1989)
[10] Arlian et al., The journal of allergy and clinical immunology, Vol. 104, No. 4, 852(1999)
[11] Schober G. et al., Journal of the British Society for Allergy and Clinical Immunology, Vol.22, No.6, 618-626(1992)
[12] Dotterud LK et al., Allergy, 50, 788-793(1995)
[13] Sakaguehi M. et al., Allergy, 47, 55-57(1992)
[14] Norback D. et al., Occup. Environ. Med., 52, 388-395(1995)
[15] Sporik R. et al., Clin. Exp. Allergy, 23,740-746(1993)
[16] Owen S. et al., 355(8686), 396-397(1990)
[17] Mosbech H. et al., Clin. Exp. Allergy, 21,351-353(1991)
[18] Harving H. et al., Allergy, 49, 866-870(1994)
[19] Cunningham M. J., Building and Environment, Vol.34, No.5,523-536(1999)
[20] Discover. Vol.19, No.9, 18 (1998)
[21] Chan Yueng M. et al., Clin. Exp. Allergy, 25,240-283(1995)
[22] De Andrade et al., Allergy, 50, 142-146(1995)
[23] Arrude LK et al., Clin. Exp. Allergy, 21,433-439(1991)
[24] Kueh J. et al., Clin. Exp. Allergy, 24, 229-237(1994)
[25] Fischer M et al., Zentralbi Hyg Umweltmed, 196, 258(1994) Hegarty
[26] Hegarty J. M. et al., Respir. Med., 89, 279-284(1995)
[27] Gaynor IR T., Hughes J. F., Medical & Biological Engineering & Computing Vol. 36, No.5,615-620(1998)
[28] Harvilicz, Helena, Chemical Market Reporter Vol.255 No.2 (Jan. 11 999) p.20
[29] EP 0 168 243, 11 July 1974
[30] Kniest F. M. et al., Journal of Aerosol Science, Vol.23, No. suppl. 1, S551-S554(1992)
[31] Anon, Textile-Industries-Dyegest-Southem-Africa, 14(10), 5(1995)
[32] Allergy-Relief-Products-Ltd., Medical-Textiles, April, 6-7(1991)
[33] Gore-and-Associates-(UK)-Ltd-WL., Medical-Textiles, November, 5-6(1993)
[34] Brzezinski-S et al., Fibers-and-Textiles-in-Eastem-Europe, 4(3-4), 124-125 (1996)
[35] Teijin Ltd., Medical-Textiles, January, 2(1997)
[36] Warner J.A. et al.,Clin. Exp. Allergy, 23,297-286 (1993)
[37] Kniest, F.M., Journal of Aerosol Science, Vol.22, No. suppl. 1, S827-S830(1991)
[38] Bossard et al., International Textile Bulletin, Dyeing/Printing/Finishing(English Edition) Vol.41 4th Quarter 3(1995)
[39] Bossard, Revista-de-la-Industrial-Textil, 372, 76-81 (1999)
[40] Bossard, Mel liand-Textiberichte, E195, 735-736(1999)
[41] Bossard, International-Carpet-Yearbook, 2000, 22-24(2000)
[42] Carlier-F, Industrial Textile, 1270(11), 67-68(1995)
[43] Technisehe-Textilien, 2000, 43(1): E3
[44] Gacen-J, Revista-de-la-Industria-Textil, 373, 41-45(1999)
[45] High-Performance-Textiles, Nov., 2(1999)
[46] Schobesberger-CP, Asian Textile Journal, 8(4), 127-130(1999)
[47] International Dyer, 184(2), 38-39(1999)
[48] Lewis, R.D. American Industrial Hygiene Association Journal p.606-613(1998)
[49] 刘长令，农药科学与管理，1998年第2期，p28
[50] Mitsubishi Chemical Industries Limited Technical "Bulletin Pyrethroid Insecticide: MAVRIK" (1984)
[51] Georghiou, George P. et al., The occurrence of resistance to pesticides in arthropods, Food and Agriculture Organization of the United Nations, 1991 Doc.
[52] 见里朝下(日本理化学研究所微生物药理研究室主任)，新农药的开发，1984年8月在上海农药所所作的学术报告
[53] Y. Katsuda et al., JP 156,335(1975)
[54] C. A. Henrick et al., Pestic. Sci., 11,224(1980)
[55] 熊怀棱丸，有机合成化学学会志，42，786 (1980)
[56] CA. Henrick etal., Pestic Sci., 11,224(1980)
[57] 吉冈宏辅，有机合成化学学会志，42(9)，809(1984)
[58] 顾可权等，华东师范大学学报No．4,73(1981)
[59] Elliott M. et al., Nature, 246, 169(1973)
[60] U.S.P. 4,243,819
[61] JP78-121731
[62] U.S.P. 4,260.633
[63] U.S.P. 4,226,802
[64] 李达文等，实用有机化学手册，399(1981)
[65] 顾可权，拟除虫菊酯，82(1984)
[66] Org. Syn., Coll., Vol.4, 792(1963)
[67] E.von Bisehoff et al., Allergologie, 9, 45(1986)
[68] E.Petri et al., Allerologie, 5, 109(1982)