2-芳氨基-3-羟乙基喹唑啉-4(3H)-酮衍生物的合成及生物活性

以取代2-氨基苯甲酸(1)为原料,经系列反应合成关键中间体β-乙氧酰基膦亚胺(4),再与芳基异氰酸酯、乙醇胺进行三组份串联的氮杂-Wittig反应,合成了一系列2-芳氨基-3-羟乙基-4(3H)-喹唑啉酮衍生物6.目标分子的结构通过IR,1H NMR,MS和元素分析确证,并进一步测试了目标化合物对烟草青枯菌的室内抑菌活性.结果表明,虽然所有化合物的抗菌活性抑制率均低于参照药物噻菌铜,但若喹唑啉酮母环附加有取代基时,化合物的抑菌活性得到显著的提高.由此可见,对喹唑啉酮母环进行修饰也不乏是一种改进其生物活性的有效途径.     

4-氧代-3（4H）-喹唑啉-5-羧酸的合成

以2-氨基-6-甲基苯甲酸为起始原料,通过合环反应生成两种4-氧代-3(4H)-喹唑啉-5-羧酸衍生物(1a, 1b), 1a, 1b分别经高锰酸钾氧化合成了4-氧代-3(4H)-喹唑啉-5-羧酸（2a, 2b）,其结构经¹H NMR, ¹³C NMR和MS表征。研究了投料比｛r［n(高锰酸钾) :n(5-甲基-3(4H)-喹唑啉-4-酮)］｝和反应温度等对收率的影响。结果表明：在最佳反应条件（r=7:1,中性高锰酸钾氧化,于90 ℃反应）下合成2总收率可达66%。     

新型含4-苯基-5-硫亚基-1,2,4-三唑曼尼希碱的喹唑啉酮类衍生物的设计合成及其生物活性研究

以喹唑啉-4-酮为起始原料,经五步反应合成了9个新型的含4-苯基-5-硫亚基-1,2,4-三唑曼尼希碱的喹唑啉酮类衍生物6a~6i,通过1H NMR、13C NMR、IR和元素分析对它们的结构进行了表征,并用X射线单晶衍射法测定了3-[(1-吗啉甲基-4-苯基-5-硫亚基-4,5-二氢-1H-1,2,4-三唑-3-基)甲基]喹唑啉-4(3H)-酮(6e)的晶体结构.初步生物活性测试结果表明,绝大部分该类化合物在200μg/m L浓度下对水稻白叶枯病菌和柑橘溃疡病菌都表现出了优良的抑制活性;在50μg/m L浓度下该类化合物对所测六种真菌都具有一定的抑制活性.     

对甲基苯磺酸亚铈催化一锅法合成取代2,3-二氢-4(1H)-喹唑啉酮

以对甲基苯磺酸亚铈为催化剂,靛红酸酐、醛和铵盐或伯胺为原料,在乙醇水溶液中三组分一锅法合成了一系列单取代和双取代2,3-二氢-4(1H)-喹唑啉酮衍生物。考察了溶剂条件及催化剂用量对产率的影响。经催化剂循环研究,催化活性无明显变化。产物的结构通过熔点、IR、1H NMR、13C NMR、质谱和元素分析进行测定和结构表征。     

一步法合成噻唑并[3,2-b](1,2,4)-三唑类衍生物的研究

以3-芳基-5-巯基-1,2,4-三唑为原料, 在酸性条件下与乙酰丙酮和乙酰乙酸乙酯一步成环, 制备得到12种新的2-芳基-5-取代-6-甲基噻唑并[3,2-b](1,2,4)-三唑类衍生物. 所有化合物结构经IR, 1H NMR, 13C NMR 和MS及元素分析确证.     

新型双腙基喹唑啉类衍生物的合成及其抑菌活性

以邻氨基苯甲酸为起始原料,设计并合成了17个新型的双腙基喹唑啉类衍生物,其结构经1H NMR,13C NMR,IR,MS和元素分析表征.初步生物活性测试结果表明,部分化合物对小麦赤霉菌、辣椒枯萎菌和苹果腐烂菌有一定的抑制活性.     

2-取代苯氨基喹唑啉衍生物的合成及抗肿瘤活性研究

以2,4-喹唑啉二酮为起始原料,通过氯代、Suzuki偶联和芳环亲核取代反应得到一系列2-取代苯氨基喹唑啉衍生物,并经~1H NMR,~(13)C NMR和HRMS进行结构确证.应用溴化噻唑蓝四氮唑(MTT)法对目标化合物进行了初步体外抗肿瘤细胞增殖活性研究.结果表明,部分化合物具有较好的体外抗肿瘤细胞增殖活性,其中活性化合物4u和4v对Hela,A549和MCF-7三种肿瘤细胞株的增殖均有明显抑制作用.     

3’-叠氮-3’-脱氧胸苷-α-羟基膦酸酯衍生物的合成

在碱性条件下, 抗病毒核苷衍生物3’-叠氮-3’-脱氧胸苷(AZT)-5’-氢亚膦酸二酯与芳香醛加成反应得到4个3’-叠氮-3’-脱氧胸苷-α-羟基膦酸酯类衍生物, 通过31P NMR, 1H NMR, ESI-MS及元素分析对其结构进行了表征确认.     

N-{3-氯4-[(3-氟苄基)氧基]苯基}-6-碘喹唑啉-4-胺的合成工艺改进

以2-胺基-5-碘苯甲酸为起始原料,经四步反应合成了新型喹唑啉类抗肿瘤药物拉帕替尼的关键中间体-N-{3-氯4-[(3-氟苄基)氧基]苯基}-6-碘喹唑啉-4-胺,总收率77.9%,其结构经1H NMR和ESI-MS确证.Williamson醚化反应的最佳条件为:4-(6-碘喹唑啉-4-基氨基)-2-氯苯酚(5)30.0 mmol,K2CO3 24.8 g,18-冠-6 0.79 g,KI 0.49 g,丙酮250 mL.于35℃反应12 h,收率90.1%.     

水相中微波辅助合成喹唑啉-4(3 H)-酮类衍生物的研究

开展了2-卤代苯甲酰胺与腈类化合物反应生成喹唑啉-4(3H)-酮类衍生物的微波辅助合成研究。结果表明:在微波辅助条件下,生成的喹唑啉-4(3H)-酮类衍生物的速率均较常规加热条件下增大,并且2-碘代苯甲酰胺比2-溴苯甲酰胺活性更高。一系列的喹唑啉-4(3H)-酮衍生物被高效地合成出来,最高产率达到89%。     

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.