植物内生真菌抗植物病原真菌活性物质的研究

植物内生真菌的代谢产物中存在一系列具有多样性结构的抗植物病原真菌的活性化合物(AFC)。本文以化合物结构为线索,对植物内生真菌所产生的具有抗植物病原真菌活性的生物碱、肽类、萜类、甾体、醌、有机酸、酯类等化合物的结构,对病原菌的抑制效果及其寄主植物等几方面进行了总结。从3个方面简单介绍了农用抗生素的作用机制,即作用于真菌细胞壁、细胞膜,以及抑制真菌蛋白质的生物合成。最后对AFC作为新型农用抗生素来源的前景进行了展望,其具有作为先导化合物,开发高效、低毒、无公害农用抗生素的巨大潜力。     

噻吩并嘧啶酮衍生物的合成及其抑菌活性

利用三组分氮杂Wittig反应,以磷亚胺2、对氯苯基异氰酸酯和酚,合成了16个未见文献报道的2-芳氧基-3-对氯苯基-3,5,6,7-四氢-4H-环戊二烯并[4,5]噻吩并[2,3-d]-嘧啶-4-酮衍生物,产率52～74%。通过IR、1H NMR、MS和元素分析对目标化合物的结构进行了表征。初步探讨了所合成化合物的抑菌活性,结果显示所合成的化合物对真菌的抑制活性优于对细菌的抑制活性,对桔青霉菌的抑制活性在65.2%以上,其中5n的抑菌率最高,达到89.1%。在化合物对细菌的抑制活性中,对绿脓杆菌的抑菌率较好,在52.8～73.0%之间,对金黄色葡萄球菌的抑制活性最低,在43.3～65.5%之间。     

氟康唑衍生物的设计合成及体外抗真菌活性研究

为了寻找活性更好的抗真菌化合物,基于已有的计算机辅助药物设计结果,保留氟康唑母体结构必需药效团,设计、合成了22个含对甲酚和胸腺嘧啶的氟康唑新衍生物.目标化合物的结构经1H NMR、元素分析和ESI-MS确证,初步体外抗真菌活性试验结果表明,化合物5l对7种真菌都表现出了较好的抗真菌活性(烟曲霉菌除外),化合物5a～5e,5g,5h,7a和7b对不同真菌表现出了一定的抗真菌活性.炔丙基取代氨基侧链结构的引入有利于提高该类目标化合物体外抗真菌活性,值得进一步深入研究.     

2-芳氧基-3-对氟苯基-3,5,6,7-四氢-4H-环戊二烯并[4,5]噻吩并[2,3-d]-嘧啶-4-酮衍生物的合成及其抑菌活性

利用三组分氮杂Wittig反应, 以三氢环戊二烯并噻吩基三苯基膦亚胺、对氟苯基异氰酸酯和酚, 合成了13个未见文献报道的2-芳氧基-3-对氟苯基-3,5,6,7-四氢-4H-环戊二烯并[4,5]噻吩并[2,3-d]-嘧啶-4-酮衍生物, 产率58%～73%. 通过IR, 1H NMR, MS 和元素分析对目标化合物的结构进行了表征. 初步探讨了所合成化合物的抑菌活性, 结果显示所合成的化合物对真菌(桔青霉菌)的抑制活性优于对细菌的抑制活性.     

普罗托品衍生物的合成及其抗菌活性研究

以小果博落回中分离的普罗托品为原料,对其十元氮杂环和苯环进行结构修饰,合成了12种衍生物,采用ESI-MS、~1H NMR和~(13)C NMR谱对其结构进行表征。以醚菌酯为阳性对照,采用菌丝生长速率法筛查了目标物在50μg·mL~(-1)时对12种常见植物病原真菌的体外抑制活性,发现大多数化合物对供试菌具有不同程度的抑制活性。其中,P4和P11的抗菌活性最好,两者对玉米弯孢病原菌的抑制活性高于醚菌酯,抑制率分别为47.78%和44.86%。由此可见,当普罗托品的14-位羰基被还原为羟基后,部分化合物的抑菌活性提高;将十元环转化为两个稠和的六元环后,关环产物的抑菌活性普遍增强。     

异黄烯衍生物的合成及其抑菌活性

光甘草定（Glabridin）作为光果甘草（Glycyrrhiza glabraL.）中主要异黄酮类活性成分之一,对多种植物病原菌具有明显的抑菌活性。基于光甘草定的结构,对其进行衍生化,有望开发出新型植物源农药。本文以邻羟基苯甲醇为起始原料,通过亲核取代、季鏻盐化和分子内维蒂希反应3步反应合成了12个3-芳基异黄烯衍生物（5a～5l）,其结构经¹H NMR、 ¹³C NMR和MS确证。采用菌丝生长速率抑制法测试了目标化合物对草莓灰霉病菌、西瓜枯萎病菌、马铃薯早疫病菌和烟草赤星病菌的抑制活性。结果表明：化合物5k对草莓灰霉病菌抑制活性较强（抑制率68.4%）;化合物5g对马铃薯早疫病菌的抑制率（85.0%）明显高于光甘草定（61.9%）;化合物5j对多种真菌病原体均表现出一定的抑制活性。     

前胡内酯肟酯衍生物的合成及其抑制乙酰胆碱酯酶活性评价

本文以香豆素类化合物前胡内酯为先导化合物,设计合成了12个前胡内酯肟酯衍生物,所有目标化合物经熔点、~1H NMR和MS进行结构确证。体外抑制乙酰胆碱酯酶(AChE)活性评价结果表明,在1μmol/mL浓度下,目标化合物4a和4k对AChE具有较强的抑制活性,其抑制率分别达到58.05%和66.27%。初步构效关系研究表明,引入吲哚环能提高前胡内酯对AChE的抑制活性。通过分子对接方法考察了化合物4k与AChE结合的模式,发现目标化合物可以和AChE的催化活性中心部位结合。     

植物内生真菌抗菌活性物质的研究进展

植物内生真菌的代谢产物中存在一系列具有多样性结构的抗菌活性化合物.对植物内生真菌所产生的抗菌活性物质的结构、对细菌和真菌的抑制效果,以及这些内生真菌的寄主植物等几方面进行了综述.简单讨论了植物内生真菌-寄主植物之间的化学生态学关系、植物内生真菌代谢物的研究价值.希望通过这些活性物质的研究能够开发出更多新型强活性抗生素.     

含1,2,3-三氮唑结构的1,5-苯并硫氮杂?的合成及其抑真菌活性

设计合成了三类含1,2,3-三氮唑结构的1,5-苯并硫氮杂?化合物3-(1H-1,2,3-三氮唑)-4-芳基-2,5-二氢-1,5-苯并硫氮杂?(5a～5f)、3-(2H-1,2,3-三氮唑)-4-芳基-2,3-二氢-1,5-苯并硫氮杂?(6a～6f)和3-(1H-1,2,3-三氮唑)-4-芳基-2,3,4,5-四氢-1,5-苯并硫氮杂?(7a～7f).研究了中间体及目标产物的合成条件,分离出其中两个副产物并进行了结构确定.目标产物的抑真菌活性测试表明,化合物5a～5f对真菌具有良好的抑制作用,对新生隐球菌的抑制效果尤为突出.初步抑真菌构效关系研究表明, 1H-1,2,3-三氮唑环和C=C双键是化合物5a～5f抑真菌活性的关键官能团.     

新型N'-芳基亚甲基-N-(4-取代苯甲酰氧基噻唑-2-基)取代苯甲酰腙的合成与生物活性

利用生物活性亚结构拼接原理,将活性酰腙亚结构与活性噻唑环亚结构进行拼接,设计合成了14个新型N'-芳基亚甲基-N-(4-取代苯甲酰氧基噻唑-2-基)取代苯甲酰腙衍生物.所有目标化合物经1H NMR、IR、质谱及元素分析等手段进行了表征,部分化合物还经过13C NMR进行了确证.抗肿瘤测试结果表明,该系列化合物表现出明显的抗肿瘤活性,其对人口腔上皮癌细胞株(KB)的抑制活性优于对鼻咽癌细胞株(CNE2)的抑制活性;采用离体平皿法对目标化合物进行杀菌活性测试,测试菌种为:小麦赤霉菌、水稻纹枯霉菌、黄瓜灰霉菌、番茄早疫菌、烟草赤星菌和黄瓜炭疽菌.结果表明,在1.0×10-4 g/m L浓度下,目标化合物对部分菌种表现中等抑菌活性.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

Synthesis of pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles by Curtius reaction in Morita-Baylis-Hillman derivatives

Synthesis of substituted pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles from the Morita-Baylis-Hillman derivatives of acrylates via saponification followed by Curtius reaction is described.     

正丁胺对激光染料荧光谱影响的研究

用正丁胺作为碳源,采用射频辉光放电制备碳膜,选用激光染料R6G和聚乙二醇混合液作为蒸气源,采用单源热蒸发,在蒸发室与染料同时沉积得到混合膜,用拉曼光谱和红外光谱分析了碳膜的结构和键合方式,分析表明:碳膜中存在胺基团和氢原子.混合膜的荧光谱测量结果表明,认为正丁胺对染料荧光谱的影响是因为胺基和氢原子的存在.     

Cu0-catalysed 1,3-dipolar cycloadditions of α-amino acid derived N,N-cyclic azomethine imines to ynones

A series of 20 CuAIAC reactions between eight 4-acylamino substituted pyrazolidine-3-one-1-azomethine imines and four terminal ynones were performed using Cu⁰ as catalyst. The corresponding fluorescent cycloadducts were obtained in very high yields upon simple workup. Thus, Cu-metal turned out to be a better catalyst than Cu^I in terms of yield and ease of isolation. Availability of azomethine imines, mild reaction conditions, and simple workup enable a “click” access to libraries of densely substituted 2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-ones. Reactivity of differently substituted dipoles was evaluated experimentally and by quantum chemical methods (DFT).     

Synthesis and antioxidative/anti-inflammatory activity of novel fullerene–polyamine conjugates

(E)-4-(Fullerenopyrrolidin-1-yl)-3-methylbut-2-enoic acid and its corresponding succinimidyl ester, readily obtained through Prato-type modification of C₆₀, were used for the selective N-acylation of polyamines. The thus obtained conjugates were evaluated for their antioxidative and anti-inflammatory activity and their cytotoxicity was determined. Members of this family of compounds showed interesting anti-lipid peroxidation, anti-lipoxygenase and anti-inflammatory activity and comparable cytocompatibility to spermidine.