本文關(guān)鍵詞：2-取代氨基環(huán)烷基磺酰胺合成與殺菌活性構(gòu)效關(guān)系研究　出處：《沈陽農(nóng)業(yè)大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 2-取代氨基環(huán)烷基磺酰胺 N-烷基化反應(yīng) 化學(xué)合成 殺菌活性 構(gòu)效關(guān)系

【摘要】：以具有很好殺菌活性的環(huán)己磺菌胺為先導(dǎo)化合物,經(jīng)過還原氨化制備得到中間體2-氨基環(huán)烷基磺酰胺,再與鹵代烷烴、取代芐溴、2-氯乙基苯、3-氯丙基苯、2-鹵代乙酸酯、5-氯甲基吡啶、5-氯甲基噻唑、N-取代-2-氯乙酰胺進(jìn)行N-烷基化反應(yīng)合成了八種不同類型的2-取代氨基環(huán)烷基磺酰胺共59個化合物(Ⅳ-1～Ⅳ-59)。所有化合物的結(jié)構(gòu)均通過核磁氫譜、核磁碳譜、高分辨質(zhì)譜、元素分析、紅外譜圖確認(rèn),此外,Ⅳ-8,Ⅳ-16,ⅣV-47這三個化合物還通過了 X-射線單晶衍射的確認(rèn)。采用菌絲生長抑制法對所有化合物進(jìn)行殺菌譜篩選,殺菌譜篩選試驗(yàn)對象有黃瓜灰霉菌(Botrytsic cinerea)、水稻稻瘟菌(Pyricularia grisea)、水稻紋枯菌(Rhizoctoniasolani Kuhn)、小麥根腐病菌(Bipolari sorokiniana)、辣椒疫霉(Phytophthora capsici)、禾谷鐮刀菌(Fusarium graminearum Schw.)、玉米大(Exserohilum turcicum(Pass.)Leonard et Suggs)共七種病原菌,篩選結(jié)果顯示化合物對黃瓜灰霉菌和水稻稻瘟菌有很高的防效,在50μg/mL下,有28個化合物對灰霉菌的抑制率達(dá)到70%以上,有5個化合物對水稻稻瘟菌的抑制率是100%。為進(jìn)一步驗(yàn)證目標(biāo)化合物對灰霉菌和稻瘟菌的活性,對其進(jìn)行了殺菌毒力測定。選用三種采自遼寧省不同地區(qū)的黃瓜灰霉菌株CY-09,HLD-15,DL-11以及稻瘟菌。殺菌毒力測定結(jié)果表明:取代基是取代芐基、取代苯乙基、取代甲基噻唑以及N-取代-2-氯乙酰胺這四類時化合物表現(xiàn)較高的抑制活性,其中表現(xiàn)最好的是5-氯甲基噻唑類,以化合物Ⅳ-24為例:對CY-09,HLD-15,DL-11三種灰霉菌的EC50值分別是3.17μg/mL,1.41 μg/mL,2.37 μg/mL 均低于對照藥劑腐霉利(10.3 μg/mL,6.03 μg/mL,4.04 μg/mL)、嘧霉胺(-,3.88 μg/mL,2.79 μg/mL)的EC50值,與啶酰菌胺和嘧菌環(huán)胺相比也有很好的抑制效果。此外,其對稻瘟菌的EC50值是4.62μg/mL低于對照藥劑稻瘟靈的(EC50=6.11μg/mL)。采用活體盆栽法對化合物進(jìn)行活體試驗(yàn),結(jié)果表明:在黃瓜活體盆栽試驗(yàn)中有6個化合物的抑制率達(dá)到90%,而對照藥劑的抑制率分別是多菌靈(59.6%),腐霉利(83.5%),嘧霉胺(82.0%),嘧菌環(huán)胺(88.6%),再番茄活體盆栽試驗(yàn)中,化合物ⅣV-38(88.1%),ⅣV-39(79.0%),ⅣV-41(87.8%)的防治效果均高于啶酰菌胺(78.2%),嘧霉胺(50.4%),腐霉利(65.7%)。綜合離體和活體條件下的生物活性,選出活性較高的化合物Ⅳ-24對其進(jìn)行室內(nèi)初步藥害試驗(yàn)。試驗(yàn)表明:在高濃度700μg/mL時,化合物Ⅳ-24對番茄幼苗和黃瓜幼苗的株高和葉片量均未產(chǎn)生藥害。構(gòu)效關(guān)系研究表明:取代基R3為烷烴類和羧酸脂類時化合物活性較低;胺基與苯環(huán)之間的碳鏈長度對活性影響較大,取代苯乙基的活性取代芐基取代苯丙基的活性,苯環(huán)上連有氟原子、溴原子等化合物活性有明顯提高;取代甲基噻唑和取代甲基吡啶作為兩類雜環(huán)取代基,均具有較高的活性,但取代噻唑類的活性明顯高于取代吡啶類;N-取代-2-氯乙酰胺類化合物總體活性很高,但當(dāng)取代基在3-位和5-位時化合物基本無活性,取代基在苯環(huán)的2-位和4-位時,化合物活性較高,氟和溴原子連接在2-位和4-位時活性最高;改變環(huán)烷基結(jié)構(gòu)(R1)發(fā)生變化時活性也有很大變化,六元環(huán)的活性高于五元環(huán)和七元環(huán),環(huán)烷基上連接的取代基團(tuán)越大活性越差。本論文對2-氨基環(huán)烷基磺酰胺進(jìn)行衍生化合成和殺菌活性測定,最終篩選出兩類活性優(yōu)異的取代基,分別是取代甲基噻唑類和N-取代-2-氯乙酰胺類,這些研究為后續(xù)的研發(fā)奠定了基礎(chǔ)。
[Abstract]:To have good bactericidal activity of cyclohexyl sulfonyl amine bacteria as the lead compound through the reductive amination of prepared intermediate 2- amino naphthene sulfamide, and halogenated hydrocarbons, substituted benzyl bromide, 2- chloride, ethyl benzene, propyl benzene chloride 3-, 2- haloacetate, 5- chloromethylpyridine, 5- chloromethyl thiazole. N- replace -2- chloroacetamides N- alkylation of eight different types of synthesis of 2- substituted amino naphthene sulfamide 59 compounds (IV -1 ~ IV -59). The structures of these compounds were characterized by 1H NMR, 13C NMR, MS and elemental analysis, infrared spectra confirmed, in addition -8 -16, IV, IV, IV V-47 these three compounds are also confirmed by the X- ray diffraction. The mycelium growth inhibition method for screening of all compounds bactericidal spectrum, spectrum bactericidal screening test object Botrytis cinerea (Botrytsic cinerea), rice (rice blast fungus Pyricularia grisea ), Rhizoctonia solani (Rhizoctoniasolani Kuhn), wheat root rot (Bipolari sorokiniana), Phytophthora capsici (Phytophthora capsici), Fusarium graminearum (Fusarium graminearum Schw.), maize (Exserohilum turcicum Leonard ET (Pass.) Suggs) a total of seven kinds of pathogenic bacteria, screening results showed that the control effect of compound is very high cucumber grey mold and rice blast bacteria, 50 g/mL, 28 compounds inhibited the Botrytis cinerea rate reached more than 70%, there are 5 compounds on the inhibition of rice blast bacteria rate is 100%. for further validation purpose activity compounds on Botrytis cinerea and Magnaporthe grisea, the the sterilization toxicity test selected three collected from different areas of Liaoning Province Botrytis cinerea strains CY-09, HLD-15, DL-11 and Magnaporthe grisea were measured. The results show that the substituent is bactericidal toxicity of substituted benzyl, substituted phenyl substituted ethyl, methyl thiazole and N- substituted -2- chloride 涔欓叞鑳鴻繖鍥涚被鏃跺寲鍚堢墿琛ㄧ幇杈冮珮鐨勬姂鍒舵椿鎬，

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