Enantioselective Copper(II)‐Catalyzed Conjugate Addition of Indoles to β‐Substituted Unsaturated Acyl Phosphonates

The first copper‐catalyzed enantioselective conjugate addition of indoles to β‐substituted unsaturated acyl phosphonates was successfully realized by using a heteroarylidene‐tethered bis(oxazoline) ligand. The reaction features high efficiency, cheap catalyst and broad generality. In the case of either β‐alkyl‐ or β‐aryl‐substituted unsaturated acyl phosphonates, the 3‐indolyl adducts were achieved in high yields with good to excellent enantioselectivities (up to 97% ee). The 3‐indolyl adducts can serve as important intermediates in the synthesis of indole alkaloids.

     

LSD1小分子抑制剂的合成及抗肿瘤活性研究

设计并合成了一系列以苯甲酰肼类结构为母核的赖氨酸特异性组蛋白去甲基化酶1(LSD1)小分子抑制剂,并研究其体外抗肿瘤活性。首先,通过体外酶水平单浓度抑制实验进行了初步评价,并随后进一步考察目标化合物对多种LSD1高表达肿瘤细胞株增殖的抑制作用,化合物结构经质谱及核磁共振表征确证。活性评价结果显示,3-(((3R,5S)-3,5-二甲基吗啉代)磺酰基)-N'-(7-羟基-2,3-二氢-1H-茚-1-亚基)苯甲酰肼、N'-(1-(5-氯-2-羟基苯基)亚乙基)-3-(((3R,5S)-3,5-二甲基吗啉代)磺酰基)苯甲酰肼和N'-(4-氯-7-羟基-2,3-二氢-1H-茚-1-亚基)-3-((4-吗啉代哌啶-1-基)磺酰基)苯甲酰肼可显著抑制肿瘤细胞的增殖,并有4个目标化合物对体外多种LSD1高表达的肿瘤细胞株增殖有抑制作用,其中3-(((3R,5S)-3,5-二甲基吗啉代)磺酰基)-N'-(7-羟基-2,3-二氢-1H-茚-1-亚基)苯甲酰肼对BGC823、HCT116、A2780s的半数抑制浓度分别为0.32、0.54、0.90μmol/L。     

Highly refractive thiazole-containing polyimides: a structural property comparison

Highly refractive, thermally stable, and solution processable polyimides (PIs) were synthesized by the introduction of thiazole units, thioether linkages, and phenyl or nitrophenyl groups into the polymer backbones. These PIs were prepared via the polycondensation of two diamine monomers, 5,5′-thiobis(2-amino-4-phenyl-thiazole) (DA-1) or 5,5′-thiobis(2-amino-4-(3-nitrophenyl)thiazole) (DA-2), with various aromatic dianhydrides(a–d). The bulky pendant phenyl or nitrophenyl units as well as the non-coplanar conformations because of ortho-sulfide linkages endowed the resulting PIs with excellent solubility in organic solvents. These PIs showed outstanding thermal stability, with 10% weight loss temperatures exceeding 492 °C under nitrogen and 475 °C in air atmosphere, while their glass transition temperatures were in the range of 239–278 °C. In general, the synergic effects of thiazole groups, phenyl or nitrophenyl substituents, and thioether linkages provided PIs with very high refractive indices of up to 1.7646 at 632.8 nm, along with small birefringences (<0.0085) and high Abbe’s numbers. The structure–property relationships of the analogous PIs containing phenyl or nitrophenyl substituents groups were also studied in detail by comparing the results.     

Ruthenium catalyzed regioselective copolymerization of acetophenone and α,ω-dienes

Summary This paper reports a novel ruthenium catalyzed regioselective copolymerization reaction between acetophenone and ,-dienes such as divinyltetramethyldisiloxane and divinyldimethylsilane which leads respectively to copoly(3,3,5,5-tetramethyl-4-oxa-3,5-disila-1,7-heptanylene/2-acetyl-1,3-phenylene) and copoly(3,3-dimethyl-3-sila-1,5-pentanylene/2-acetyl-1,3-phenylene). This reaction involves the ruthenium catalyzed insertion of the carbon-carbon double bonds of ,-dienes into the aromatic C–H bondsortho to the acetyl group of acetophenone. Similar ruthenium catalyzed reactions between acetophenone and alkenes to yield monomericortho alkyl substituted acetophenones have been recently reported.¹     

单取代烷烃的熵和吉布斯自由能与分子结构的关系

将单取代烷烃RX(X=OH、SH、NH2、Cl、Br、I、NO2、CN等)分子结构分为两个区域R和X来提取分子结构参数,从三方面影响因素:烷基R、取代基X、R与X相互作用来定量关联RX标准摩尔熵及标准摩尔生成吉布斯自由能。获得了已有实验测定的单取代烷烃RX标准摩尔熵及标准摩尔生成吉布斯自由能,并以烷基的碳原子数、取代基X对所研究单取代烷烃热力学性质的贡献值,烷基的极化效应指数与取代基电负性的乘积三参数为变量,建立定量相关模型,采用留一法交叉验证这些方程,结果表明,模型方程都具有良好的稳定性和预测能力。     

Synthesis of Novel Aminothiazole Derivatives as Promising Antiviral,Antioxidant and Antibacterial Candidates

It is well-known that thiazole derivatives are usually found in lead structures, which demonstrate a wide range of pharmacological effects. The aim of this research was to explore the antiviral, antioxidant, and antibacterial activities of novel, substituted thiazole compounds and to find potential agents that could have biological activities in one single biomolecule. A series of novel aminothiazoles were synthesized, and their biological activity was characterized. The obtained results were compared with those of the standard antiviral, antioxidant, antibacterial and anticancer agents. The compound bearing 4-cianophenyl substituent in the thiazole ring demonstrated the highest cytotoxic properties by decreasing the A549 viability to 87.2%. The compound bearing 4-trifluoromethylphenyl substituent in the thiazole ring showed significant antiviral activity against the PR8 influenza A strain, which was comparable to the oseltamivir and amantadine. Novel compounds with 4-chlorophenyl, 4-trifluoromethylphenyl, phenyl, 4-fluorophenyl, and 4-cianophenyl substituents in the thiazole ring demonstrated antioxidant activity by DPPH, reducing power, FRAP methods, and antibacterial activity against Escherichia coli and Bacillus subtilis bacteria. These data demonstrate that substituted aminothiazole derivatives are promising scaffolds for further optimization and development of new compounds with potential influenza A-targeted antiviral activity. Study results could demonstrate that structure optimization of novel aminothiazole compounds may be useful in the prevention of reactive oxygen species and developing new specifically targeted antioxidant and antibacterial agents.     

Thermoplastic elastomers by hydrogen bonding

Summary Poly(butadienes) were modified by an ene-reaction using 4-phenyl-1, 2,4-triazoline-3,5-dione (1) 3-nitro-4-hydroxyphenyl-1, 2,4-triazoline-3,5-dione (2) and 4-hydroxyphenyl1, 2,4-triazoline-3,5-dione (3). The resulting hydrogen bond complexes between urazole groups act as thermoreversible crosslinks and alter the melt rheological behaviour. While dimeric chelate-like complexes are formed in polymers modified with 1 or 2, a three dimensional structure of hydrogen bond complexes is formed if 3 is used as the modifying agent. The thermorheologically complex behaviour of the latter material is interpreted by structural changes in the three dimensional structure with temperature.     

A Demonstration of the Reactivity—Selectivity Principle for the Thiol—Disulfide Interchange Reaction

Equilibrium constants for the reaction of aryl thiol anions with hydroxyethyl disulfide have been measured which, along with literature data, demonstrate a slope of 1.21 for a plot of log K^S− (R'S- + RSSR ⇌ R'SSR + -SR) vs pKa. Rate constants were measured also for these endothermic reactions of aryl thiol anions with hydroxyethyl disulfide and also for the exothermic reactions of alkyl thiol anions with the mixed disulfide of mercaptoethanol and 4-nitro-2,3,5,6-tetrafluorothiophenol. These kinetic data, obtained over a range of K^S− of 10²¹, show the gradual curvature expected for Hammond postulate type behavior. A quantitative measure of this curvature in terms of the Marcus formalism was carried out for these two data sets along with four others having more moderate values of ΔG. The data were fit with a value for the intrinsic barrier, λ/4 = 11.6 kcal, and a value for the work term W_r = 4.0 kcal. A comparison is made of these values with the similar values found for alkyl, proton and acyl transfer reactions. The importance of using a variety of substrates with a series of bases or nucleophiles, rather than a single substrate, is discussed, as are the cause for curvature other than Hammond postulate behavior.     

Electrochemical study of azo-azulene compounds

An electrochemical study of several azo-azulene compounds (Az-NN-Y, where Y = substituted phenyl, pyridine, thiazole) was performed with cyclic and differential pulse voltammetry, as well as rotating-disk electrode methods. The objective of this work was to characterize their electrochemical properties and establish the influence of donor and acceptor substituents on azulene and azo group behaviour. Calculations were performed, using quantum mechanics-based methods, to correlate electrochemical reactivity with structure. Satisfactory correlations were found between experimental oxidation and reduction potentials as well as calculated ionization potentials and LUMOs.     

Manganese(III) mediated synthesis of A2B Mn(III) corroles: A new general and green synthetic approach and characterization

A new general and green synthetic protocol for the synthesis of manganese(III) metallocorroles has been developed from substituted aryl aldehydes and 5-(4-nitrophenyl)dipyrromethane using manganese salt as template. This is the first report in the synthesis of corroles: the formation of direct CC bond through metal initiation. This method allows higher working concentrations than those previously reported. The new A₂B manganese(III) metallocorroles were synthesized in good yield for different applications. The single crystal X-ray structure of 10-(3,4,5-fluorophenyl)-5,15-bis(4-nitrophenyl)manganese(III) corrole is also reported and shows that manganese atom is situating atop on macrocyclic plane.     

Enzymatic resolution of 1-hydroxy-2,3-dihydroindene and 1-hydroxy-1,2,3,4-tetrahydronaphthalene derivatives using lipases

1-Hydroxy-3-methyl-2,3-dihydroindene and 1-hydroxy-1,2,3,4-tetrahydronaphthalene derivatives were kinetically resolved with lipases by transesterification using vinyl esters or butyric anhydride as acyl donors. These results are discussed in considering the influence of acyl donors and with reference to Prelog's proposal that certain enzymes exhibit ‘product stereospecificity’.     

2,2-二(4-羟基-3,5-二硝基苯基)丙烷和2,2-二(4-羟基-3-硝基苯基)丙烷热分解动力学研究

用热分析方法(TG,DTA)、热分解气相色谱和红外光谱等联合手段,对双酚A的二硝基取代产物和四硝基取代产物[2,2-二(4-羟基-3,5-二硝基苯基)丙烷和2,2-二(4-羟基-3-硝基苯基)丙烷]的热稳定性和热分解反应动力学进行了研究,发现它们的稳定性与硝基取代的数目有关,热分解具有失去一端并带走一个甲基的共同机理,然而热分解动力学方程形式不同分别是:dα/dt=50.90e(-E/RT)(1-α)和dα/dt=59.06 e(-E/RT)(1-α)3,从电荷分布均衡点出发对上述现象进行理论探讨。     

Phase transfer catalyzed polymerization of 4-hydroxy-3,5-dimethylbenzyl alcohol and copolymerization of 4-bromo-2,6-dimethylphenol with 4-hydroxy-3,5-dimethylbenzyl alcohol

Summary This paper describes the phase transfer catalyzed (PTC) polymerization of 4-hydroxy-3,5-dimethylbenzyl alcohol (1) and the PTC polymerization of 4-bromo-2,6-dimethylphenol (19) in the presence of 4-hydroxy-3,5-dimethylbenzyl alcohol (1). At 89% conversion the homopolymerization of 1 produced a 95% yield of 4,4-dihydroxy-3,3,5,5-tetramethyldiphenylmethane (3) and a 5% yield of oligomers. The polymerization of 19 in the presence of 1 resulted in poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) polymers in 71 to 89% yields. The 200 MHz ¹H-NMR spectroscopy analyses of the resulting PPO polymers indicate that they represent a mixture of bifunctional (PPO-2OH) and monofunctional (PPO-OH) polymers. A radicalanion mechanism was proposed to account for both the homopolymerization and the copolymerization reactions.     

Cobalt-Molybdenum Sulfide Catalysts Prepared by In Situ Activation of Bimetallic (Co-Mo) Alkylthiomolybdates

Unsupported cobalt-molybdenum sulfide catalysts were prepared from bimetallic CoMo alkyl precursors by in situ activation during the hydrodesulfurization (HDS) of dibenzothiophene (DBT). The bimetallic CoMo precursors were prepared by reaction of tetraalkylammonium thiomolybdate salts, (R₄N)₂MoS₄ (where R = H, methyl, butyl, pentyl or hexyl), with CoCl₂ in water at a Co/Mo molar ratio of 0.3. These catalysts exhibit a Swiss-cheese-like morphology, high surface areas (from 52 up to 320 m²/g), high content of carbon (C/Mo = 2.2-3.3) and type IV adsorption-desorption isotherms of nitrogen. The in situ activation of these tetraalkylammonium thiobimetalate precursors leads to a mesoporous structure with pore size ranging from 2 to 4.5 nm. X-ray diffraction showed that the structure of unsupported cobalt-molybdenum sulfide catalysts corresponds to a poorly crystalline structure characteristic of 2H-MoS₂ with low-stacked layers. The nature of the alkyl group strongly affects both the surface area and the HDS activity. The catalytic activity is strongly enhanced when using carbon-containing precursors; the CoMo catalysts prepared by in situ activation of Co/[N(C₄H₉)₄]₂MoS₄ presents the highest HDS activity. The highest surface area of the catalysts was observed for the CoMo catalyst formed from Co/[N(C₆H₁₃)₄N]₂MoS₄.     

2-丁基-6-硝基吲哚的合成

介绍了一步关环合成2-丁基-6-硝基吲哚的新方法。室温氮气保护下,2-氨基-4硝基苯酚与三氟乙酰酐反应进行氨基保护,得到的2-（N-三氟甲基乙酰基）氨基-4-硝基苯酚与N-苯基双（三氟甲烷磺酰）亚胺（PhNTf2）在强碱 NaH作用下,生成三氟甲基磺酸酯,收率82.6%。之后,70～80 ℃氮气保护下,Pd(PPh3)4催化剂作用,与正己炔一步关环合成2-丁基-6-硝基吲哚,收率33.3%。产物结构经红外光谱、核磁共振和质谱检测并证实。将目标产物进行单晶培养,经单晶X衍射检测表征,阐明了结构。     

Preparation and characterization of novel grafted polyethylene based azo-polymers bearing oligo(ethylene glycol) spacers

Novel grafted azo-polymers were prepared from commercial low density polyethylene plates (PE). First, precursor polymers were synthesized by reacting PE in the presence of acryloyl chloride using gamma radiation. Further esterification of the resulting grafted polymers with four new amino-nitro substituted azobenzene derivatives bearing oligo(ethylene glycol) segments: N-methyl-N-{4-[(E)-(4-nitrophenyl)diazenyl]phenyl}-N-(5-hydroxy-3-oxapentas-1-yl)amine (RED-PEG-2), N-methyl-N-{4-[(E)-(4-nitrophenyl)diazenyl]phenyl}-N-(8-hydroxy-3,6-dioxaoctas-1-yl)amine (RED-PEG-3), N-methyl-N-{4-[(E)-(4-nitrophenyl)diazenyl]phenyl}-N-(11-hydroxy-3,6,9-trioxaundecas-1-yl)amine (RED-PEG-4) and N-methyl-N-{4-[(E)-(4-nitrophenyl)diazenyl]phenyl}-N-(17-hydroxy-3,6,9,12,15-pentaoxaheptadecas-1-yl)amine (RED-PEG-6) led to the formation of branched azo-polymers. These polymers were characterized and their thermal and optical properties were studied. Besides, the influence of the irradiation dose, irradiation time and the structure of the dyes on the properties of the obtained polymers are discussed.     

Voltammetric oxidation of Hantzsch 1,4-dihydropyridines in protic media: substituent effect on positions 3,4,5 of the heterocyclic ring

A detailed study was done of the electrochemical oxidation of some 1,4-dihydropyridine (1,4-DHP) derivatives in order to determine the influence of the substituents in the heterocyclic ring. Two types of derivatives were synthesized, namely, 3,5-(substituted)-4-(5′-nitro-2′-furyl)-1,4-DHP for series A, and 3,5-dicarboethoxy-4-(substituted or non-substituted)-1,4-DHP for series B. Voltammetry, coulometry, controlled potential electrolysis, UV-vis spectroscopy and GC-MS techniques were employed to collect data that permitted to postulate oxidation mechanisms in a protic medium. In acid media, at pH < 4, all derivatives follow oxidation mechanisms obeying the ECE sequence. However, at pH > 4, series A derivatives follow an ECEC sequence, while series B derivatives obey a DISP1 mechanism. In both cases, the uptake of proton at N-1 by the OH⁻ ion of the media was the rate-determining step.     

Highly Enantioselective Synthesis of Chiral Tetrahydroquinolines and Tetrahydroisoquinolines by Ruthenium‐Catalyzed Asymmetric Hydrogenation in Ionic Liquid

Asymmetric hydrogenation reactions of quinolines and 3,4‐dihydroisoquinolines using the chiral cationic ruthenium complex Ru(TsDPEN) [TsDPEN=N‐(p‐toluenesulfonyl)‐1,2‐diphenylethylenediamine] as catalyst in neat imidazolium ionic liquids have been investigated. The catalytic performance was influenced by the anion of the ionic liquids for both substrate classes. A range of 2‐alkyl‐substituted 1,2,3,4‐tetrahydroquinolines and 1‐alkyl‐substituted 1,2,3,4‐tetrahydroisoquinolines was obtained in high yields with up to >99% ee. Interestingly, the hydrogenation of quinoline derivatives bearing a carbonyl group was selective for the CN (quinoline) over the CO (ketone) bonds, while such a unique chemoselectivity was not observed in methanol. Furthermore, the ruthenium catalysts could be easily recycled at least 5 times in the asymmetric hydrogenation of 3,4‐dihydroisoquinoline by solvent extraction. To further facilitate the recovery of catalyst and reduce the use of organic solvent, a thin film of ionic liquid containing Ru(TsDPEN) was supported on silica gels. This supported ionic liquid‐phase catalyst was effective in the asymmetric hydrogenation of quinoline, and could be recycled at least 6 times by simple filtration.

     

Cyclisierungen mit 1-Nitro-2-anilino-äthylenen

Cyclizations with 1-nitro-2-anilino-ethylenes The reaction of 1-nitro-2-anilino-2-methylthio-ethylenes 1 with oxalyl chloride yields the substituted 4-nitropyrrol-2,3-diones 4 , and with chlorocarbonyl-sulfenylchloride the 5-nitro-thiazolones 6 . The methylthio group from 6 can be exchanged by amines. From 1-nitro-2,2-bis(anilino)ethylenes 2 – available from 1-nitro-2,2-bis(methylthio)-ethylene and anilines – and the same reagents, the substituted 2-nitromethylene-imidazolidine-4,5-diones 5 and the thiazolo[4,5-d]thiazoledione 9 result. The condensation of 1-nitro-2-anilino-2-hydrazino-ethylene 3 with derivatives of carboxylic acids yields 2-nitromethyl-s-triazole 12 , with diacetyl the substituted 3-nitromethylene-as-triazine 13 .     

Method of analysis for deoxynivalenol and zearalenone from cereal grains

A method was developed to determine deoxynivalenol and zearalenone in corn, wheat, oats, rice and barley. The toxins are extracted with methanol/water (50:50, v/v) (2×) and partially purified by partitioning into ethyl acetate and then defatting with acetonitrile-petroleum ether. Toxins are isolated by silica gel column chromatography. Interfering materials are removed from the column with benzene; zearalenone is eluted with benzene/acetone (95:5, v/v), and after a column wash of chloroform/methanol (95:2, v/v), deoxynivalenol is eluted with chloroform/methanol (95:5, v/v). Zearalenone is quantitated by thin-layer chromatography and deoxynivalenol by gas-liquid chromatography of the trimethylsilyl derivative. The detection limit is about 0.02 μg/g for each toxin. Recoveries of added toxins varied with substrate and level of toxins. Recovery of deoxynivalenol ranged from 58% for 1 ppm in rice to 108% for 1 ppm in corn. Average recoveries for all levels (1, 2 and 5 ppm) ranged from 69% for barley to 89% for oats. Recovered zearalenone ranged from 40% for 5 ppm in wheat to 100% for 1 ppm in barley. Average recoveries for zearalenone at 1, 2 and 5 ppm varied from 53% for wheat to 87% for rice.