4-(哌啶-4-基)-1H-吡咯-3-甲酰胺类衍生物盐酸盐的合成及其抗菌活性研究

以Boc-4-哌啶甲醇为起始原料,经Swern氧化、羟醛缩合、Knorr吡咯合成法、氨基保护、酯水解、酰胺化、脱保护及成盐反应合成了一系列4-(哌啶-4-基)-1H-吡咯-3-甲酰胺类衍生物盐酸盐,经~1H NMR,~(13)C NMR和MS-ESI等确证结构。用抑菌环法测试了此类衍生物对大肠杆菌和金黄葡萄球菌生长的抑制作用,结果显示目标化合物能够不同程度地抑制大肠杆菌的生长,其中4-(哌啶-4-基)-1H-吡咯-3-(N-甲基-N-丙基甲酰胺)盐酸盐对大肠杆菌的抗性显著,最高抑制率达96%。     

4-(4-吗啉)哌啶盐酸盐的合成

4-甲酸乙酯哌啶与溴苄反应,再经酰胺化和氨化反应制得关键中间体4-氨基-1-苄基哌啶(5);5与2,2-二溴二乙醚经环化反应制得N-苄基-4-(4-吗啉)哌啶,再经成盐,加氢合成了4-(4-吗啉)哌啶盐酸盐(1,总收率24.9%),1的结构经1HNMR,IR和GC-MS确认。     

1-(4-氨基苯基)-2-(1-哌啶基)-1-丙酮盐酸盐的合成及其光引发性能

1-(4-氨基苯基)-2-(1-哌啶基)-1-丙酮盐酸盐的合成及其光引发性能;氨基苯乙酮;水溶性;光引发剂     

N-(1-哌啶-2-乙基)-β-(5-硝基-2-呋喃)丙烯酰胺盐酸盐的示波极谱和脉冲极谱分析

N-(1-哌啶-2-乙基)-β-(5-硝基-2-呋喃)丙烯酰胺盐酸盐(F30385)是β-(5-硝基-2-呋喃)丙烯酸的一种衍生物,由化工部上海医药工业研究院章元琅等继文献[1,2]之后,新合成的治疗日本血吸虫病的有效药物。我们曾用极谱法研究过 F30066等[3]和F30111等β-(5-硝基-2-呋喃)丙烯酸的衍生物,但     

Cobimetinib 消旋体的合成

以3-羟基氮杂环丁烷盐酸盐为原料,经Cbz保护和氧化反应制得1 苄氧羰基氮杂环丁烷-3-酮(3); 3与N-亚硝基哌啶发生亲核反应后与2,3-二氟-(2-氟-4-碘氨基）苯甲酸发生缩合反应,最后经氯化氢脱亚硝基和碱化合成了Cobimetinib消旋体,其结构经¹H NMR和HR-MS（ESI）确证。     

3-芳基-4-[4''-(2,2,6,6-四甲基哌啶-1-氧)]-1,2,4-三唑啉-5-硫酮类的合成

本文用芳酰肼和2,2,6,6-四甲基-4-异硫氰基-哌啶-1-氧以无水乙醇为溶剂,在氩气保护下反应,制得八种1-芳酰基-4-[4'(2,2,6,6-四甲基哌啶-1-氧)]氨基硫脲(1),继而研究1在几种碱催化下脱水的环化反应。试验结果表明,只有在1mol的K2CO3水溶液中,才能较满意地使1环化,得到预期的3-芳基-4-(4'-2,2, 6,6-四甲基哌啶-1-氧)-1,2,4-三唑啉-5 硫酮。     

顶空-气相色谱法测定盐酸贝尼地平中4种溶剂残留量

盐酸贝尼地平化学名为(4RS)-2,6-二甲基-4-(3-硝基苯基)-1,4-二氢-3,5-吡啶二甲酸-3-[(3RS)-1-苯甲基-3-哌啶基]酯-5-甲酯盐酸盐。盐酸贝尼地平是日本协和发酵工业公司在70年代后期为改善硝苯地平副作用而合成、筛选得到的一种新型持续性钙拮抗剂[1-2]。     

苯并吡喃[3,4-c]吡啶-5-酮类化合物的合成

以4-酮-3-甲酸甲酯哌啶盐酸盐为原料, 通过分子间环加成和N-烷基化反应, 合成了一系列潜在的多巴胺D₄受体配基苯并吡喃[3,4-c]吡啶-5-酮类化合物, 并用¹H NMR, IR, ESI-MS, 元素分析对其进行了表征.     

新型CCR5拮抗剂——N-【1-{5-溴-2-[(4-氯苄基)氧基]苄基}-4-哌啶基】-N-乙基吡啶甲酰胺的合成

以5-溴水杨醛和4-氯苄氯为原料,通过消去、还原及溴化反应制得中间体4-溴-2-溴甲基-1-[(4-溴苄基)氧]苯(3);哌啶-4-酮经Boc保护、还原等4步反应制得中间体N-乙基-N-(4-哌啶基)吡啶甲酰胺(7);3与7通过消去反应合成了一种新型CCR5拮抗剂——N-【1-{5-溴-2-[(4-氯苄基)氧基]苄基}-4-哌啶基】-N-乙基吡啶甲酰胺,其结构经1H NMR,13C NMR和ESI-MS表征。     

新型2-溴苯酰胺类小分子CCR5拮抗剂的合成及其GTPγS结合性

以2-羟基-5-溴苯甲醛为起始原料,经取代,还原和NBS溴化反应制得5-溴-2-(4-氯苯甲氧基)溴甲苯(3);以4-哌啶酮盐酸盐为原料,经保护,还原和缩合反应制得N-烯丙基-2-溴-N-哌啶基苯酰胺(7);3和7经取代反应合成了一个新型的非肽类小分子CCR5拮抗剂——N-烯丙基-2-溴-N-{N-[2-(4-氯苯甲氧基)-5-溴苄基]-4-哌啶基}苯酰胺(8),总产率32.5%,其结构经1H NMR,13C NMR,IR和ESI-MS表征。用GTPγS法测试了8的生物结合性。结果表明:8的生物结合性与TD0232接近,其IC50为(8.12±0.3)nmol·L-1。     

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.