【作者】 朱兆勇；

【导师】 杨春龙；

【作者基本信息】 南京农业大学 ， 应用化学， 2009， 硕士

【摘要】 Tetramic acid类天然产物可从海洋和陆地生命体中分离得到,它们结构复杂多变,同时也表现出了显著的抗肿瘤、抗细菌、抗真菌、抗病毒以及除草等活性。人们通过对吡咯环上取代基的修饰,已合成了大量的tetramic acid衍生物,其中部分化合物具有显著的生物活性。为了筛选具有更高活性的新型tetramic acid化合物,我们设计合成了两个系列的化合物,即5-芳亚甲基-3-乙酰基tetramic acid肟醚与1-烷基-3-乙酰基tetramic acid肟醚,并测定了它们的除草活性及抑制真菌活性,通过解析单晶结构,还确定了化合物的几何异构。本文首先研究了5-芳亚甲基-3-乙酰基tetramic acid肟醚类化合物的合成及生物活性研究。以甘氨酸乙酯为原料,经过3步反应得到3-乙酰基tetramic acid,与取代苯甲醛反应得到5-芳亚甲基-3-乙酰基tetramic acid,再与烷氧基胺反应得到24个5-芳亚甲基-3-乙酰基tetramic acid肟醚类化合物(Ⅰ)。采用IR,1HNMR, MS和元素分析确认了各化合物结构。用X-Ray单晶衍射分析了化合物Ie和Ij的单晶结构,这两个晶体都属于三斜晶系,空间群P-1,Ie的晶胞参数：a=7.440(5)A,b=9.486(6)A,c=12.745(8)A,a=69.035(7)°,β=89.336(7)°,γ=74.838(8)°,Z=2,Dc=1.235g.cm-3,V=807.4(9)A3,F(000)=320。Ij的晶胞参数：a=8.8536(15)A,b=9.0461(15)A,c=16.010(3)A,α=105.610(3)°,β=92.074(3)。,γ=115.446(2)°,Z=2,Dc=1.281g.cm-3,V=1098.1(3)A3,F(000)=448。采用平皿法测定了该类化合物的除草活性,发现在100μg/mL浓度下无明显的除草活性。采用菌丝生长速率法测定了该类化合物对小麦赤霉菌、小麦纹枯菌和黄瓜炭疽菌的抑制活性,在100μg/mL浓度下有近50%的化合物对黄瓜炭疽菌抑制活性超过了40%。其中化合物Ia,In和Ip对黄瓜炭疽菌的ECso分别达到1.15,30.43和40.13μg/mL。本文同时研究了1-烷基-3-乙酰基tetramic acid肟醚类化合物的合成及生物活性。以溴乙酸乙酯为原料,与烷基胺反应得到N-取代甘氨酸甲(乙)酯,再经3步反应得到1-烷基-3-乙酰基tetramic acid,最后与烷氧基胺反应得到20个1-烷基-3-乙酰基tetramic acid肟醚类化合物,并用IR,1HNMR, MS和元素分析确认了结构,对其中的化合物Ⅱr进行了X-Ray单晶衍射分析,该晶体属于单斜晶系,空间群C2/c,晶胞参数：a=32.78(9)A,b=5.195(14)A,c=18.025(5)A,β=102.734(3)°,Z=8,Dc=1.235g.cm-3,V=2993.8(14)A3,F(000)=1200。采用平皿法测定了该类化合物的除草活性,在100μg/mL浓度下,此类化合物对油菜和稗草根长具有较强的抑制活性,其中化合物Ⅱs对油菜和稗草根长抑制率分别达到了78.1%和85.2%。但各化合物对稗草芽长抑制作用很弱。采用菌丝生长速率法测定了该类化合物抗真菌活性,在100μg/mL浓度下,对小麦赤霉菌、小麦纹枯菌和黄瓜炭疽菌均有一定抑制作用。所有化合物的抗真菌活性均高于tenuazonic acid。有13个化合物对黄瓜炭疽菌的抑制作用超过了50%,其中Ⅱm抑制作用达到了70.0%。更多还原

【Abstract】 Hundreds of natural tetramic acids with diversified structures have been isolated from land and ocean organism and were found to exhibit antitumor, antiviral, antibacterial and herbicidal activities. The pyrrolidine-2,4-dione ring was modified and a lot of tetramic acid derivatives among of which possessed good biological activities were synthesized. In order to find more novel compounds showing better biological activities, two series tetramic acid oxime ether derivatives were designed and synthesized, and the fungicidal and herbicidal activities of them were also tested. Three single crystal structures of the compounds were obtained to further confirm the structures.First, synthesis and biological activities of novel3-acetyl-5-arylidene-tetramic acid oxime ether derivatives were studied. The compounds (Z)-3-acetyl-5-arylidene-4-hydroxypyrroline-2-ones were prepared by the reaction of3-acyl tetramic acid which was synthesized with the glycine as the starting materials with substituted benzaldehydes.(Z)-3-acetyl-5-arylidene-4-hydroxypyrroline-2-ones were reacted with O-alkyl hydroxylamines to afford twenty four3-acetyl-5-arylidene tetramic acid oxime ether derivatives(Ⅰ) respectively. The structures of these compounds were confirmed by IR,1H NMR, MS and elemental analysis. The single crystals of Ie and Ij suitable for collecting data on the X-ray diffraction machine were obtained. Both the crystals were in triclinic system with space group P-1, The unit cell parameters of Ie as follows:a=7.440(5)A,6=9.486(6)A, c=12.745(8)A, a=69.035(7)°,β=89.336(7)°, γ=74.838(8)°, Z=2, Dc=1.235g.cm-3, V=807.4(9)A3, F(000)=320. The unit cell parameters of Ij as follows: a=8.8536(15)A,b=9.0461(15)A, c=16.010(3)A, α=105.610(3)°,β=92.074(3)°, γ=115.446(2)°, Z=2, Dc=1.281g.cm-3, V=1098.1(3)A3, F(000)=448. The herbicidal activities of the target compounds were determined with Brassica napus and Echinochloa crusgalli (L.) Beauv at a concentration of100μtg/mL. The result showed that the herbicidal activities of all compounds were quite weak. The fungicidal activities were tested by radial growth inhibition method using Fusarium gramineaum, Rhizoctonia cerealis, and Colletotrichum orbiculare at a concentration of100μg/mL. The results showed that most of the title compounds exhibited noticeable fungicidal activities against Colletotrichum orbiculare and a certain degree of fungicidal activities against Fusarium gramineaum and Rhizoctonia cerealis. The compounds la, In, and Ip displayed the remarkable activities against Colletotrichum orbiculare with EC50values of1.15,30.43and40.13μg/mL, respectively.Second, synthesis and biological activities of novel3-acetyl-l-alkyl-tetramic acid oxime ether derivatives were studied. The starting material ethyl bromoacetate was reacted with alkylamines to afford N-alkylglycine ethyl ester which was treated to abtain3-acetyl-1-alkyl-tetramic acid via three-steps reactions.3-Acetyl-l-alkyl-4-hydroxypyrroline-2-ones were reacted with O-alkyl hydroxylamines afforded twenty3-acetyl-l-alkyl tetramic acid oxime ether derivatives(Ⅱ) respectively. Structures of all new compounds were confirmed by IR,1H NMR, MS and elemental analysis. The single crystal of Ⅱr was abtained to further determain the structure of title compounds. The crystal was in monoclinic system with space group C2/c, and the unit cell parameters as follows:a=32.78(9)A,b=5.195(14)A, c=18.025(5)A, β=102.734(3)°, Z=8, Dc=1.235g.cm-3, V=2993.8(14)A3,F(000)=1200. The results of herbicidal activities showed that these compounds exhibited noticeable inhibition against the root of Brassica napus and Echinochloa crusgalli (L.) Beauv, but weak inhibition against the bud of Echinochloa crusgalli (L.) Beauv. The inhibition of compound Ⅱs against the root of Brassica napus and Echinochloa crusgalli (L.) Beauv was78.1%and85.2%, respectively. The results of fungicidal activities indicated these compounds exhibited noticeable fungicidal activities against Fusarium gramineaum, Rhizoctonia cerealis and Colletotrichum orbiculare at a concentration of100μg/mL. Fungicidal activities of most of these compounds against Colletotrichum orbiculare were more than50%, Ⅱm with the highest activity up to70.0%. The inhibition of all these compounds against three test fungi was better than tenuazonic acid.更多还原