己唑醇衍生物的合成及其抑菌性能研究
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摘要
为了提高己唑醇的杀菌广谱性以及杀菌活性,参考己唑醇的化学结构,以戊酰氯和取代苯为原料,经傅克酰基化、Corey-Chaykovsky环氧化反应、开环反应得到8种化合物,所有化合物均经质谱和核磁共振氢谱确证。选取常用木材腐朽菌——白腐菌(彩绒革盖菌、乳白耙齿菌)、褐腐菌(密粘褶菌、绵腐卧孔菌)和霉菌——黑曲霉作为实验菌株,采用滤纸片法研究8种目标化合物的抑菌活性。结果表明:在质量分数0.5%~2.0%范围内,除化合物A4、A5外,其余化合物对彩绒革盖菌、乳白耙齿菌、密粘褶菌、绵腐卧孔菌和黑曲霉均有一定的抑菌效果,其抑菌能力随着药液浓度的增加而增强。通过与己唑醇对照可知,化合物C3总体抑菌效果最好,并优于己唑醇;化合物C2对腐朽菌的抑菌效果优于己唑醇,对黑曲霉的抑菌效果弱于己唑醇;化合物A1、A2、A3、C1的抑菌效果均弱于己唑醇;化合物A4、A5对木材腐朽菌和霉菌几乎没有抑制作用。可见,卤素(F、Cl)对苯环2,4-二位上的取代、叔醇碳上异丁基的引入均有利于提高目标化合物的抑菌活性。
In order to improve broad-spectrum characteristics and antimicrobial activities of hexaconazole on wood-rotting fungi and moulds,valeryl chloride and substituted benzene were used as raw materials and eight compounds were synthesized by Friedel-Crafts acylation,Corey-Chaykovsky reaction and 1,2-epoxide opening reaction based on the chemical structure of hexaconazole. These compounds were confirmed by MS and1H-NMR. Wood-rotting fungi such as white-rot fungi( Coriolus versicolor and Irpex lacteus),brown-rot fungi( Gloeophyllum trabeum and Postia placenta) and mould( Aspergillus niger)were used to test the antimicrobial activities of the compounds by filtering paper method. The results showed that the compounds had obvious antimicrobial activities on the fungi in the concentration range of0. 5%- 2. 0% except compounds A4 and A5,and the antimicrobial activities increased with the increase of solution concentration. The antimicroial activities of compound C3 were the best and significantly better than those of hexaconazole. The antimicrobial activities of compound C2 on wood-rotting fungi were superior to hexaconazole; however,such effects on mould were worse than those of hexaconazole. The antimicrobial effects of compounds A1, A2, A3 and C1 were not as good as hexaconazole, and compounds A4 and A5 had little inhibitory activities on wood-rotting fungi. The conclusion was that the introduction of isobutyl group in tertiary alcohol carbon,2,4-dichlorophenyl and 2,4-difluorophenyl was conducive to increasing antimicrobial activities of target compounds.
In order to improve broad-spectrum characteristics and antimicrobial activities of hexaconazole on wood-rotting fungi and moulds,valeryl chloride and substituted benzene were used as raw materials and eight compounds were synthesized by Friedel-Crafts acylation,Corey-Chaykovsky reaction and 1,2-epoxide opening reaction based on the chemical structure of hexaconazole. These compounds were confirmed by MS and1H-NMR. Wood-rotting fungi such as white-rot fungi( Coriolus versicolor and Irpex lacteus),brown-rot fungi( Gloeophyllum trabeum and Postia placenta) and mould( Aspergillus niger)were used to test the antimicrobial activities of the compounds by filtering paper method. The results showed that the compounds had obvious antimicrobial activities on the fungi in the concentration range of0. 5%- 2. 0% except compounds A4 and A5,and the antimicrobial activities increased with the increase of solution concentration. The antimicroial activities of compound C3 were the best and significantly better than those of hexaconazole. The antimicrobial activities of compound C2 on wood-rotting fungi were superior to hexaconazole; however,such effects on mould were worse than those of hexaconazole. The antimicrobial effects of compounds A1, A2, A3 and C1 were not as good as hexaconazole, and compounds A4 and A5 had little inhibitory activities on wood-rotting fungi. The conclusion was that the introduction of isobutyl group in tertiary alcohol carbon,2,4-dichlorophenyl and 2,4-difluorophenyl was conducive to increasing antimicrobial activities of target compounds.
引文
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[21]Deutsches Institute fur Normung.Medical microbiology:susceptibility testing of microbial pathogens to antimicrobial agentspart 9:regression line analysis for the correlation of inhibition zone diameter(IZD)and minimum inhibitory concentration,DIN58940-9-2007[S/OL].2007-08--11[2014-08--10].http:∥www.instrument.com.cn/application/standard/171439.html.
[22]中华人民共和国卫生部.消毒技术规范[S].北京:中华人民共和国卫生部,2006.Ministry of Health of the People’s Republic of China.Technical standard for disinfection[S].Beijing:Ministry of Health of the People’s Republic of China,2006.
[2]EVANS P.Emerging technologies in wood protection[J].Forest Products Journal,2003,53(1):14-22.
[3]孙芳利,鲍滨福,陈安良,等.有机杀菌剂在木竹材保护中的应用及发展展望[J].浙江农林大学学报,2012,29(2):272-278.SUN F L,BAO B F,CHEN A L,et al.Application and prospect of organic biocides in timber preservation[J].Journal of Zhejiang A&F University,2012,29(2):272--278.
[4]SCHULTZ T P,NICHOLAS D D,PRESTON A F.Perspective:a brief review of the past,present and future of wood preservation[J].Pest Management Science,2007,63(8):784--788.
[5]席丽霞,蒋明亮.三唑类木材防腐剂研究进展[J].林产工业,2013,40(4):3-8.XI L X,JIANG M L.Review on the research progress of triazole wood preservatives[J].China Forest Products Industry,2013,40(4):3-8.
[6]OTTO E.Tebuconazole-A new triazole fungicide for wood preservation[C]∥The 22nd Annual Meeting of International Research Group on Wood Protection.Kyoto:IRGWP,1991:20-24.
[7]GERBRAND R,KLAVER C J.Synergistic combinations of cyproconazole:CA,2088714[P/OL].1993-08--05[2014-08-10].http:∥worldwide.espacenet.com/searchResults?AP=CA19932088714.
[8]American Wood Protection Association.Standard for Tebuconazole(TEB),Propiconazole(PPZ),Cyproconazole(CPZ)[S].New York:America Technical Committees,2011:41--46.
[9]WAKELING R N,MAYNARD N P,NARAYAN R D.A study of the efficacy of antisapstain formulations containing triazole fungicides[C]∥The 24th Annual International Research Group on Wood Preservation.London:IRGWP,1993:41--48.
[10]KCIICHIRO I,HITOSHI E.Wood preservative composition:JP,2003252705[P/OL].2003--09--10[2014--08--10].http:∥worldwide.espacenet.com/searchResults?AP=JP20020051953
[11]FUJIMOTO K.Antifungal and preservative composition for wood:JP,2006056041[P/OL].2006--03-02[2014--08--10].http:∥worldwide.espacenet.com/publication Details/biblio?II=0&ND=3&adjacent=true&FT=D&date=20060302&CC=JP&NR2006056041A&KC=A
[12]李晓文,马星霞,蒋明亮.戊唑醇和丙环唑的耐腐性能评价[J].木材工业,2011,25(5):13--15.LI X W,MA X X,JIANG M L.Decay resistance of triazole wood preservatives containing tebuconazole and propiconazole[J].China Wood Industry,2011,25(5):13-15.
[13]李靖,刘幸平,程康华,等.三唑醇类化合物的合成及其抑菌性能研究[J].林产化学与工业,2013,33(3):115-119.LI J,LIU X P,CHENG K H,et al.Synthesis and antimicrobial properties of triazolanol compounds[J].Chemistry and Industry of Forest Products,2013,33(3):115-119.
[14]王丽,何深远,程康华.粉唑醇的化学改性及其衍生物的抑菌活性[J].东北林业大学学报,2014,42(8):152--156.WANG L,HE S Y,CHENG K H.Chemical modification of flutriafol and bacteriostasis of its ramifications[J].Journal of Northeast Forestry University,2014,42(8):152--156.
[15]席丽霞,马星霞,蒋明亮.三唑制剂的防腐及防白蚁性能[J].林业科学,2013,49(7):123--128.XI L X,MA X X,JIANG M L.Decay and termite resistant performance of triazole preservatives[J].Scientia Silvae Sinicae,2013,49(7):123-128.
[16]孙家隆.农药化学合成基础[M].北京:北京化工出版社,2008:168-169.SUN J L.Chemical synthesis of pesticides[M].Beijing:Chemical Industry Press,2008:168--169.
[17]CHOPRA D,MOHAN T P,RAO K S,et al.2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)-hexan-2-ol(hexaconazole)[J].Acta Crystallographica Sectton E-Structure Reports Online,2004,60:2410-2412.
[18]WORTHINGTON P A.Synthesis of 1,2,4-triazole compounds related to the fungicides flutriafol and hexaconazole[J].Pesticide Science,1991,31(4):457--498.
[19]王红学,李正名.2,4-二氯苯戊酮的工艺改进[J].天津化工,2007,21(5):19--20.WANG H X,LI Z M.Study on synthesis route of 2,4-dichlorophenyl ketone[J].Tianjin Chemistry Industry,2007,21(5):19--20.
[20]LI G C,WANG L Y,HUANG Y.Sulfur ylides participating domino cyclization reaction[J].Chinese Journal of Organic Chemistry,2013,33:1900-1918.
[21]Deutsches Institute fur Normung.Medical microbiology:susceptibility testing of microbial pathogens to antimicrobial agentspart 9:regression line analysis for the correlation of inhibition zone diameter(IZD)and minimum inhibitory concentration,DIN58940-9-2007[S/OL].2007-08--11[2014-08--10].http:∥www.instrument.com.cn/application/standard/171439.html.
[22]中华人民共和国卫生部.消毒技术规范[S].北京:中华人民共和国卫生部,2006.Ministry of Health of the People’s Republic of China.Technical standard for disinfection[S].Beijing:Ministry of Health of the People’s Republic of China,2006.