新型取代查尔酮-哌嗪衍生物的合成及其生物活性评价（英文）

为了寻找结构新颖的活性分子,采用活性亚结构拼接的方法,设计合成了24个未见文献报道的取代查尔酮-哌嗪衍生物,其结构经~1H NMR、~(13)C NMR和HRMS确证.分别采用小鼠巨噬细胞Raw 264.7炎症模型和噻唑蓝(MTT)法对目标化合物的体外抗炎活性和细胞毒活性进行测试,结果表明,查尔酮母核和哌嗪环上的取代基对化合物的生物活性有明显影响.特别是3,4,5-三甲氧基-4'-[N-(2-氧代丙基)-1-哌嗪基]查尔酮(11)能有效抑制NO的生成(IC50=3.81μmol/L),4-溴-4'-[N-(4'-甲基-2-氧代苯乙基)-1-哌嗪基]查尔酮(25)对三种肿瘤细胞株(Hela,A549和sk-ov-3)均表现出良好的体外细胞毒活性(IC50值分别为0.54,0.05和9.12μmol/L).     

含酰基哌嗪片段的呋喃查尔酮衍生物的合成及其抗炎活性研究

依据活性结构单元的拼合原理,以2-呋喃甲醛和4-氟苯乙酮为原料出发,经Aldol缩合、脱水、哌嗪取代反应生成4’-(1-哌嗪基)呋喃查尔酮(2)后,再与酰氯和磺酰氯反应,得到了10个未见报道的含哌嗪取代的呋喃查尔酮衍生物,其结构经~1H NMR和~(13)C NMR确证。采用小鼠巨噬细胞Raw 264.7模型初步测试了目标化合物的体外抗炎活性,结果表明,磺酰胺类化合物的抗炎活性要优于酰胺类化合物,特别是化合物4d能有效抑制NO的生成(IC_(50)=3.88μmol/L),与阳性对照药地塞米松活性相当。     

哌嗪取代查尔酮衍生物的合成及其细胞毒活性

以4-甲氧基苯甲醛与2-溴-4’-氟苯乙酮为原料,经羟醛缩合脱水、取代反应生成4-甲氧基-4’-(1-哌嗪基)查尔酮(2),再通过酰化反应合成了10个新型含哌嗪的查尔酮衍生物,其结构经~1H NMR、~(13)C NMR及HRMS确证。采用MTT法初步测试了目标化合物的体外细胞毒活性,结果表明,化合物3e和4d对肿瘤细胞株Hela和A549均表现出较好的细胞毒活性,可做进一步研究。     

3-芳基-5-噻吩基二氢吡唑磺酰胺衍生物的合成及其抗炎活性研究

二氢吡唑是一类含有多种生物活性的五元氮杂环化合物,广泛存在于各种活性天然产物结构中。本文由4-氟苯乙酮和N-甲基哌嗪经取代反应后,再与2-噻吩甲醛发生羟醛缩合生成哌嗪取代噻吩查尔酮(2)。化合物2与水合肼环化得到中间体化合物3,最后经磺酰氯衍生化,合成得到8个未见报道的3-芳基-5-噻吩基二氢吡唑磺胺衍生物(4a～4h),其结构均经IR、~1H NMR和~(13)C NMR确证。采用小鼠巨噬细胞Raw264. 7模型初步测试了衍生物的抗炎活性,结果表明,化合物4a、4e和4h具有潜在的体外抗炎活性,特别是化合物4a抑制NO生成的IC_(50)值为12. 64μmol/L,与阳性对照药地塞米松活性相当。     

3-芳基-5-噻吩基二氢吡唑磺酰胺衍生物的合成及其抗炎活性研究

二氢吡唑是一类含有多种生物活性的五元氮杂环化合物,广泛存在于各种活性天然产物结构中。本文由4-氟苯乙酮和N-甲基哌嗪经取代反应后,再与2-噻吩甲醛发生羟醛缩合生成哌嗪取代噻吩查尔酮(2)。化合物2与水合肼环化得到中间体化合物3,最后经磺酰氯衍生化,合成得到8个未见报道的3-芳基-5-噻吩基二氢吡唑磺胺衍生物(4a～4h),其结构均经IR、~1H NMR和~(13)C NMR确证。采用小鼠巨噬细胞Raw264. 7模型初步测试了衍生物的抗炎活性,结果表明,化合物4a、4e和4h具有潜在的体外抗炎活性,特别是化合物4a抑制NO生成的IC_(50)值为12. 64μmol/L,与阳性对照药地塞米松活性相当。     

4-(甲氧基噻吩基)-3-(取代苯甲酰基)-吡咯类化合物的合成与抗肿瘤活性研究

分别以2-甲氧基噻吩、3-甲氧基噻吩、3,4-二溴噻吩和取代苯乙酮为原料,经过溴甲氧基取代反应、VilsmeierHack反应、羟醛缩合和Van Leusen吡咯合成法,设计并合成了33个未见文献报道的4-取代噻吩基吡咯类化合物.其结构均经~1H NMR,~(13)C NMR及HRMS确认,同时采用噻唑蓝(MTT)法测试了目标化合物对CHO、HCT-116、MGC80-3、SGC-7901以及HUVEC细胞增殖抑制活性.结果显示,部分化合对MGC80-3细胞有较强(IC_(50)≤20μml/L)或中等(20μmol/LIC_(50)≤50μmol/L)增殖抑制作用,其中[4-(3,4-二甲氧基噻吩-2-基)-1H-吡咯-3-基](4-苯基苯基)甲酮(4a-2)和[4-(3,4-二甲氧基噻吩-2-基)-1H-吡咯-3-基](3-溴苯基)甲酮(4a-7)的IC_(50)值分别为8.6和8.5μmol/L;化合物4a-7对HCT-116细胞有中等抑制活性;化合物4a-2和4a-7对SGC-7901细胞有中等增殖抑制活性;并且几乎所有化合物对正常人体细胞HUVEC无明显抑制作用.     

溴代甲氧基二苯甲酮咪唑类化合物的合成及对过氧化氢致EA. hy 926细胞损伤的保护作用

本文旨在引入咪唑环,对溴代甲氧基二苯甲酮类化合物进行结构衍生,以发现对血管内皮细胞具有更高保护活性的化合物。通过以2-甲基-5-溴-苯甲酸为起始原料,经过酰氯化、傅克酰化、溴代、与N-溴代丁二酰亚胺(NBS)自由基取代及与取代咪唑的亲核取代等多步反应,合成了8个新型溴代甲氧基二苯甲酮咪唑类化合物。目标化合物的结构均经质谱(MS)、核磁共振波谱仪(NMR)和高分辨质谱(HRMS)进行确证。并采用噻唑蓝(MTT)法考察了目标化合物对过氧化氢损伤的EA.hy 926细胞的保护活性,结果表明,目标化合物6a、6g、6h具有显著的细胞保护活性,其半抑制浓度(EC50)分别为1.9、4.0和3.2μmol/L,优于阳性对照槲皮素(EC_(50)为18μmol/L),表明该类化合物在心血管疾病的治疗方面有潜在的应用前景。     

7-O-羧烷基化白杨素衍生物的合成及其抗癌活性

以白杨素(1)为起始原料,与溴代羧酸乙酯经取代反应制得中间体7-O-乙氧羰基烷基白杨素(3a~3d);3a~3d经水解反应合成了7-O-羧烷基化的白杨素衍生物(4a~4d),其中4b~4d为新化合物,其结构经1H NMR,13C NMR,IR和ESI-MS表征。初步的体外抗癌活性实验结果表明,3和4对人肝癌细胞Hep G2和人胃癌细胞MGC-803具有一定的抗癌活性,且大多数化合物的抗癌活性比母体化合物1强,其中6-(5-羟基-2-苯基-4H-苯并吡喃酮-7-氧)己酸(4d,IC504.04μmol·L-1)对MGC-803细胞的活性抑制作用强于阳性药物DDP(IC504.40μmol·L-1)。     

2-(取代哌嗪-1-甲基)-3-喹啉甲酸乙酯及其衍生物的合成、 表征及晶体结构

以邻硝基苯甲醛为起始原料, 经还原、Friedländer 缩合反应合成2-甲基-3-喹啉甲酸乙酯(2), 2经N-溴代丁二酰亚胺(NBS)溴代得到化合物3, 3再与N-取代哌嗪5a～5p 发生SN2亲核取代反应, 合成一系列2-(取代哌嗪-1-甲基)-3-喹啉甲酸乙酯及其衍生物6a～6p. 它们的结构通过元素分析, IR, 1H NMR, 13C NMR和MS进行了鉴定和表征, 并用X射线衍射法测定了化合物6n的晶体结构.     

新型紫罗兰酮基双查尔酮缩氨基硫脲的合成及抗肿瘤活性

根据活性亚结构拼接原理,通过紫罗兰酮与(取代)苯甲醛反应合成了紫罗兰酮基双查尔酮,然后经与氨基硫脲缩合得到一系列未见报道的新型含紫罗兰酮、查尔酮及氨基硫脲3种优势结构单元的杂化体,它们的化学结构经傅里叶变换红外光谱(FT-IR)、核磁共振波谱(~1H NMR、~(13)C NMR)、元素分析及质谱(MS)等测试技术所证实。采用溴化噻唑蓝四氮唑(MTT)法初步测定其体外抗肿瘤活性(乳腺癌细胞(MCF-7),肝癌细胞(Hep G2),肺癌细胞(A549)),结果表明,对于不同类型的肿瘤细胞,化合物展现较好的增殖抑制活性。尤其是化合物3a与3b对MCF-7细胞展现较强的抗增殖活性,半数致死量(IC_(50))值分别为10.83和7.62μmol/L,化合物3e对A549细胞显示一定的增殖抑制活性效果(IC_(50)值为13.36μmol/L),化合物3f对Hep G2细胞表现了高效的抗增殖活性(IC_(50)值为8.55μmol/L)。目标物的抗增殖活性与紫罗兰酮结构及查尔酮环上不同电子效应的取代基有关。     

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.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.