1,4-二氧喹喔啉甲醛亚胺的合成和抑菌活性

1;4-二氧喹喔啉甲醛亚胺的合成和抑菌活性;二氧喹喔啉甲醛亚胺;合成;结构表征;抑菌活性     

1,3-偶极环加成合成双-噻唑啉酮衍生物

喹喔啉甲醛;三唑醛;双席夫碱;偶极环加成;双-噻唑啉酮衍生物     

α-卤代酮与芳香二胺经氧化-缩合过程一锅法合成喹喔啉衍生物

在二甲亚砜作用下, α-卤代酮与芳香1,2-二胺反应, 得到较高产率的喹喔啉衍生物. 结果表明反应经历一个串联的氧化-缩合过程. 二甲亚砜现场氧化α-卤代酮, 生成的二羰基化合物与芳香1,2-二胺缩合成喹喔啉衍生物.     

樟脑基喹喔啉类化合物的合成及其生物活性

将D-(+)-樟脑用二氧化锡氧化制得樟脑醌,再与系列取代邻苯二胺化合物缩合,合成得到19个樟脑基喹喔啉类化合物(3a～3s),并用UV-Vis、 ¹H NMR、 ¹³C NMR、 FT-IR和HR-MS(ESI)进行结构表征。初步的抑菌和除草活性测试表明：在用药量为50 μg·mL^-1时,目标化合物对花生褐斑病菌、小麦赤霉病菌、黄瓜枯萎病菌、苹果轮纹病菌、番茄早疫病菌、玉米小斑病菌、西瓜炭疽病菌以及水稻纹枯病菌等8种植物病原菌具有一定的抑制活性,其中化合物樟脑基5,8-二溴喹喔啉3r(R¹=R⁴=Br,R²=R³=H)对苹果轮纹病菌的抑制率达78.6%,优于阳性对照百菌清。在用药量为100 μg·mL^-1时,化合物樟脑基6-氟喹喔啉3f(R³=F, R¹=R²=R⁴=H)和樟脑基7-氟喹喔啉3g(R²=F, R¹=R³=R⁴=H)对油菜胚根生长的抑制率分别为75.8%和68.5%,均优于阳性对照丙炔氟草胺。      

1,3-偶极环加成合成双-4,5-二氢-1,2,4-噁二唑啉衍生物

用2-苯基-1,2,3-三唑基-4-甲醛(1)或喹喔啉基-2-甲醛(2)与乙二胺缩合成双席夫碱3或4, 然后与α-氯代肟在三乙胺条件下发生1,3-偶极环加成得到双-4,5-二氢-1,2,4-噁二唑啉衍生物6a～6f或7a～7f. 目标化合物的结构经元素分析, IR, ¹H NMR和MS确认.     

双功能MoNi4电极实现水参与的氮杂环化合物转移氢化与脱氢

氮杂环的催化氢化在有机合成、药物研发、石油化工等领域有着重要应用.尽管发展了一系列均相和非均相催化加氢体系,但由于通常使用易燃易爆的氢气或价格昂贵且毒性较高的试剂(如:水合肼和硼氢化钠)为氢源,给安全生产及生态环境带来了严重的问题.此外,由于动力学同位素效应,氘代药物具有重要应用.氮杂环结构作为生物医药的构筑单元与关键中间体,现有的策略由于没有合适的氘源难以用于氘代氮杂环化合物的合成.因此,急需开发一种基于非贵金属催化剂和安全易得氢(氘)源的氮杂环催化氢(氘)化策略.水相中的电化学氢化可利用水电解原位产生的活性氢替代传统的氢气裂解实现有机氢化产物的合成,已成为一种理想氢化策略,被广泛应用于二氧化碳还原、硝酸根还原和生物质氢解等.本课题组前期研究已经实现了以氘水为氘源的氘代分子的高效电化学合成(Angew.Chem.Int.Ed.,2020,59,18527–18531;Angew.Chem.Int.Ed.,2020,59,21170–21175;CCS Chem.,2021,3,507–515).然而,要开发一种电化学的杂环氢化方法,一方面要克服氮杂环化合物对催化剂的毒化,另一方面要在电极表面产生大量的活性氢.因此,开发具有较好的水离解性能的非贵金属电极材料是实现氮杂芳烃电化学氢化和氘代的关键.基于上述要求,MoNi4(目前用于碱性电催化水分解制氢的活性较高的非贵金属材料)成为理想的电极材料.本文以喹喔啉(1,2,3,4-四氢喹喔啉骨架作为重要的结构单元存在于许多生物活性化合物中)作为模板底物,设计并制备了三维自支撑的MoNi4多孔纳米片为双功能电极,以水和氘水为氢源和氘源,实现了喹喔啉及其他氮杂环分子的氢化与氢化,同时实现了四氢喹喔啉的电化学氧化脱氢.制备了MoNi4纳米片阵列,利用扫描电子显微镜、透射电子显微镜、X射线衍射和X光电子能谱等手段进行表征,评估了其在碱性电解液中用于喹喔啉电化学转移氢化的性能.结果表明,MoNi4电极加速了动力学缓慢的Volmer步骤,在仅50 mV的过电势下以80％的法拉第效率实现了喹喔啉的电化学氢化.电子顺磁共振等证实水电解生成了H*,并与喹喔啉自由基阴离子偶联实现喹喔啉的氢化.同时,该电化学转移氢化方法可很好地应用于一系列喹喔啉衍生物和其他氮杂芳烃化合物.克级合成体现了该电化学转移氢化方法的潜在应用性.原位拉曼实验结果表明,在MoNi4表面形成的NiOOH是实现1,2,3,4-四氢喹喔啉氧化脱氢的重要物种.此外,以D2O代替H2O,可以较好的收率和高达99％的氘化率实现氘代氮杂环的合成.与传统的氮杂环氢化方法相比,本文的电化学转移氢化策略具有绿色、温和、高效的特点,同时拓宽了电化学氢化在合成化学中的应用.     

新型3-芳乙烯基喹喔啉-2-羧酸合成及结核杆菌亮氨酰-tRNA合成酶的抑制活性研究（英文）

使用自制的3-溴甲基喹喔啉-2-甲酸乙酯为反应物,经一锅连续的Arbuzov反应/Horner-Wadsworth-Emmons(HWE)反应/酯基水解反应,简便有效地合成了一系列结构新型的3-芳乙烯基喹喔啉-2-羧酸类化合物,并对其进行了初步的结核杆菌亮氨酰-tRNA合成酶(MtbLeu RS)抑制活性实验.结果表明(E)-3-(3-硝基苯乙烯基)喹喔啉-2-羧酸(5j)的抑制活性最好,其IC50值为14.7μmol·L~(-1),高于参考药物AN2679,具有很好的MtbLeu RS抑制剂开发潜力.利用Discovery Studio分子模拟软件CDOCKER程序进行分子模拟分析,结果表明该化合物能够与Mtb LeuRS的活性点很好的结合.而且,体外抗耻垢分枝杆菌Mycobacterium smegmatis (M. smegmatis)活性实验也发现,化合物5j的抗结核杆菌的活性最佳,其最小抑菌浓度(MIC)为15.6μg/m L与参考药物rifampicin相当.     

喹喔啉-三唑衍生物的设计与合成及其抗肿瘤活性

喹喔啉和1,2,3-三唑都是具有广泛生物活性的杂环结构母体。本文基于药物设计的拼合原理,以简单易得的邻苯二胺、苯乙炔及有机叠氮为原料,通过三组分"两步一锅法"将喹喔啉和1,2,3-三唑活性亚结构进行拼接,合成了一系列共14个新型喹喔啉-三唑衍生物(3a~3n)。该法操作简单,无需分离中间体,两步总产率52.6%~78.4%。合成的目标化合物结构经~1H NMR、~(13)C NMR和HRMS确证。初步体外抗肿瘤活性测试表明,合成的目标化合物具有一定的抗肿瘤活性。     

过氧化物酶新型荧光底物3,4-二氢-2(1H)-喹喔啉酮的反应机理及性能的研究

合成了过氧化物酶新型荧光底物3,4-二氢-2(1H)-喹喔啉酮(DHQXL). 在过氧化物酶催化下,该化合物可被H₂O₂氧化生成强荧光物质2(1H)－喹喔啉酮(QXL). 用高压液相色谱法分离得荧光产物纯品,经核磁共振谱和质谱证实其结构,确证了提出的酶催化反应机理. 对该化合物作为荧光底物的性能研究表明,它是一个很有应用前景的过氧化物酶的新型荧光底物.     

十一种2,3-二取代喹喔啉-1,4-二氧化物抗菌剂的合成与谱学研究

采用直接氧化法和Beirut反应合成了十一种抗菌剂2,3-二取代喹喔啉-1。4-二氧化物.给出了完整的UV,IR,NMR数据和有关谱学特性.EPR研究表明这些N-氧化物在溶液光解过程中生成稳定的顺磁物.从含有2,3-环丁亚基喹喔啉-1,4-氧化物(2g)的氯仿溶液光解体系记录的EPR谱得到9.69G(1N)、3.59G(2H),1.25G(2H)和0.76G(1H)等超精细分裂值,指认为1-羟基-2,3-环丁亚甲基喹喔啉-4-氧基(4).指出喹喔啉-1,4-氧化物与对萘醌化合物有结构、物性的类似性.     

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.