新型N-3位酰胺连噻唑烷-4-酮二芳基衍生物的设计合成及HIV逆转酶抑制活性

以氨基酸酯为原料,在微波辐射条件下合成了系列N-3位含酯基的噻唑烷-4-酮衍生物,经水解并酰胺缩合制备了N-3位酰胺键连接嘧啶胺的二芳基噻唑烷-4-酮衍生物.化合物通过人类免疫缺陷病毒(HIV)逆转酶(RT)试剂盒(比色法)评价了其酶抑制活性.活性结果表明,部分化合物如5bb,5bc,5cb和5cc能有效地抑制HIV逆转酶的活性,IC_(50)值分别为4.15,3.53,4.61和4.06μmol/L.构效关系表明N-3位2个碳的柔性侧链以及亲脂基如甲基的引入将有利于化合物的抗HIV逆转录酶活性.     

斑蝥素衍生物的合成、抗肝癌活性及构效关系研究

斑蝥素衍生物具有结构多样性和良好的抗肝癌活性。本文以呋喃、顺丁烯二酸酐为原料,合成了35个斑蝥素衍生物。以顺铂为阳性对照药,经MTT法测试了所合成化合物对人肝癌HepG2细胞的体外抗肿瘤活性。结果表明,化合物6d、6f、6g、6h、6i的抗肝癌活性与顺铂相当,其中,斑蝥素酰亚胺类化合物具有较好的抗肝癌活性,且当取代基为吸电子基或含氮杂环时化合物显现出较强的抗肝癌活性,该类化合物具有潜在的抗肝癌应用价值。     

肉桂酰酪胺类似物的合成与抗血小板聚集评价

为了探究肉桂酰酪胺的苯环上甲氧基取代、酪胺上羟基和酰胺上胺基被甲基化对衍生物抗血小板聚集活性的影响,以8种苯甲醛衍生物为原料,经过缩合反应及甲基化等反应制得肉桂酰酪胺类似物,经核磁共振波谱仪(NMR)、质谱(MS)、单晶衍射等技术手段表征了目标化合物结构。 基于变温核磁,探讨了化合物4a~4h中旋转异构及酰胺C-N键双键性质对氢核磁谱的影响。 采用Born比浊法对目标化合物进行活性筛选,9个类似物的活性均强于柄果花椒酰胺,特别是化合物2c、4c、4f在200 μmol/L时显示出强的抑制率,分别为50.03%、60.87%、53.33%。 该类化合物的构效关系是4位甲氧基取代对化合物的抗ADP(二磷酸腺苷)诱导血小板聚集活性最为有利,甲基化B环中的羟基和结构中的酰胺氮原子时,在某种程度上可增强化合物活性。     

新型含亲水基的噻唑烷-4-酮衍生物的合成及HIV逆转录酶抑制活性

在微波辐射条件下合成了系列C-2或N-3位含酯基的噻唑烷-4-酮衍生物,经水解或还原得到含亲水基如羧基、羟基的衍生物.化合物通过艾滋病毒逆转酶(HIV-RT)试剂盒(比色法)评价了其酶抑制活性.活性结果表明,部分化合物如8a,8b,9a,9b和14c能有效地抑制HIV逆转酶的活性.其中在N-3嘧啶环5位连有乙基的化合物8a和9a的活性最高,IC50值分别为3.02和3.06μmol·L-1.构效关系表明亲水性基团的引入对HIV逆转录酶抑制活性影响不大,而N-3位嘧啶基更有利于噻唑烷-4-酮抗HIV活性.     

具类辣素结构丙烯酰胺的合成及其抑菌和防污性能

以N-羟甲基丙烯酰胺和苯酚类化合物为原料,合成了N-(2-羟基-3-丙烯酰胺甲基-4,6-二甲基苄基)丙烯酰胺(HMABA)、N-(2-羟基-3-丙烯酰胺甲基-4,5-二甲基苄基)丙烯酰胺(AMHBA)、N-(3,5-二甲基-4-羟基苄基)丙烯酰胺(MHBA)、N-(3,6-二甲基-4-丙烯酰胺甲基-2-羟基苄基)丙烯酰胺(MAHBA)和N-(2甲氧基-4-甲基-5-丙烯酰胺甲基苄基)丙烯酰胺(MMABA)5个类辣素结构的丙烯酰胺衍生物。 通过红外光谱（IR）、核磁波谱（1H NMR）、质谱（HR-MS）和元素分析对化合物的结构进行了表征。 抑菌试验表明,HMABA对金黄色葡萄球菌和大肠杆菌的抑制效果最好,最低抑菌浓度均可达0.125 g/L。 将此5个化合物作为防污剂制备海洋防污涂料,120 d的实海结果表明,基本无污损海生物附着。     

7-二乙氨基香豆素腙及酰腙衍生物的制备及乙酰胆碱酯酶抑制活性研究

本论文采用亚活性结构拼接的方法,以7-N,N-二乙氨基-4-甲基香豆素为原料,经二氧化硒氧化,然后与取代肼和取代酰肼反应,合成了13个7-N,N-二乙氨基香豆素腙及酰腙衍生物。所有目标化合物经1H NMR和MS进行结构确证。体外抑制乙酰胆碱酯酶活性结果表明,目标化合物4a和4c对乙酰胆碱酯酶具有较强的抑制活性,其IC50值分别为42. 89和90. 32μmol/L。初步构效关系研究表明,酰腙衍生物对乙酰胆碱酯酶的抑制活性比腙类衍生物好。     

新型N-(2'-芳胺嘧啶-4'-基)-N,2,3-三甲基-2H-吲唑-6-胺衍生物的合成及其抗肿瘤活性

以3-甲基-6-硝基-1H-吲唑为原料,经N-甲基化、催化还原、亲核取代及烷基化反应制得关键中间体N-(2'-氯嘧啶-4'-基)-N,2,3-三甲基-2H-吲唑-6-胺(5);5与芳胺经亲核取代反应合成了一系列新型的N-(2'-芳胺嘧啶-4'-基)-N,2,3-三甲基-2H-吲唑-6-胺衍生物,其结构经1H NMR和MS确证。初步生物活性测试结果表明,部分化合物具有明显的抗肿瘤活性。     

藤黄酸氧化类似物的合成及抗肿瘤活性的二维定量构效关系

报道了35,40-二羟基-6-甲氧基-藤黄酸甲酯(1)、9,10-二羟基-6-甲氧基-藤黄酸甲酯(2)和2-去异己烯-2-(2-甲酰基)乙基-6-甲氧基-藤黄酸甲酯(3)的化学合成和抗肿瘤活性. 采用二维定量构效关系方法经计算机模拟与统计分析, 获得定量构效关系方程. 结果显示, 藤黄酸氧化衍生物的极性体积比、零阶价分子连接性指数、总电荷绝对值和体积与抗肿瘤活性间表现出了良好的线性关系.     

4β-氨基-4脱氧鬼臼毒素和4β-氨基-4脱氧-4'-去甲基鬼臼毒素的两种新合成方法

我们在研究抗肿瘤活性物质的基础上[1～ 5 ],注意到鬼臼类化合物具有抗癌活性 ,但其毒副作用较大 ,我们对其结构进行了改造 ,以研制活性更高而毒性更小的新的衍生物 .从以前有关鬼臼毒素及其类似物的构效关系研究中已得出以下几个方面的结构要求是保持其抗癌活性必须具备的条件 :(ａ)在4’ 位有一个酚羟基 ;(ｂ)Ｃ 4取代基位是 β构型 ;(ｃ)具有反式内酯环[6 ].研究表明 ,4 β 酰胺基的鬼臼衍生物具有较强的抗癌活性[7].而 4 β 氨基 4脱氧鬼臼毒素和 4 β 氨基 4脱氧 4’去甲基鬼臼毒素是合成此类衍生物的最重要中间体 .合成这两个化合物的…     

醚取代芳香β－醛酮衍生物的合成及抗菌活性研究

鱼腥草素具广谱的抗菌活性,其药效团为β－醛酮结构。本文以对羟基苯乙酮为原料,通过Claisen缩合、加成、缩合得到12个芳香β－醛酮衍生物,所合成化合物经过红外、核磁、质谱进行了结构表征。对所合成的化合物进行了抑菌活性测试,初步构效关系表明,烷氧基胺席夫碱可能是活性基团,酮羰基的存在对提高抗菌活性有利,苯环上取代基对抗菌活性有重要影响。     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.     

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

The review contains a concise historical account and information on the most significant researches undertaken by the staff at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences on the Chemistry of Heterocyclic Compounds. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1443–1502, October, 2008.     

Sulfur-directed metal-free and regiospecific methyl C(sp3)–H imidation of thioanisoles

Regiospecific and direct imidation of the methyl C(sp³)–H bond of thioanisoles is realized under mild and metal-free conditions with N-fluorobis(benzenesulfonyl)imide as an oxidant and nitrogen source. Proposed mechanism suggests that thionium ion intermediates and a Pummerer-type reaction are involved. The imidation has advantages such as high step-economy, excellent functionality tolerance, and regiospecificity, giving structurally diverse imidation products.     

Selective syntheses of 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones via temperature-dependent Rh(II)-carbenoid-mediated 2H-azirine-ring expansion

The Rh(II)-catalyzed reaction of 2-carbonyl-substituted 2H-azirines with ethyl 2-cyano-2-diazoacetate or 2-diazo-3,3,3-trifluoropropionate provides an easy access to 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones. These compounds can be selectively prepared from the same starting material using temperature as the only varied parameter. The 2-azabuta-1,3-diene intermediate, a common precursor for both heterocyclic products, isomerizes into 2H-1,3-oxazine under kinetic control, while 1H-pyrrol-3(2H)-one is the sole product of the reaction at elevated temperatures. According to DFT-calculations a one-atom oxazine ring contraction involving ring-opening to a 2-azabuta-1,3-diene intermediate, followed by a 1,5- and 1,2-prototropic shift leads to the consecutive formation of imidoylketene and azomethine ylide, which then further undergo cyclization to the pyrrole derivative.     

Copper catalyzed/mediated synthetic methodology for ebselen and related isoselenazolones

Scope of the copper catalyzed/mediated selenium-nitrogen coupling reaction has been studied for the synthesis of isoselenazolones. It is noticed that the 2-chloro, 2-bromo-, and 2-iodo-aryl amides substrates can be exploited in the selenium-nitrogen coupling reaction by employing 25-100 mol % of CuI/1,10-phenanthroline (L) and potassium carbonate as a base in DMF. Furthermore, electron rich 2-chloro-arylamides also underwent selenium-nitrogen coupling reaction to give biologically important selenium-nitrogen heterocycles. Also, copper-catalyzed selenium-nitrogen coupling reaction has been meticulously applied for the synthesis of diaryl diselenides having methoxy, amine, and amide functionality from respective aryl iodides in the presence of stoichiometric amount of succinimide as an external Se-N coupling partner.