Preparation of linear alpha-olefins to high-molecular weight polyethylenes using cationic alpha-diimine nickel(II) complexes containing chloro-substituted ligands

A series of alpha-diimine nickel(II) complexes containing chloro-substituted ligands, [(Ar)N=C(C10H6)C=N(Ar)]NiBr2 (4a, Ar = 2,3-C6H3Cl2; 4b, Ar = 2,4-C6H3Cl2; 4c, Ar = 2,5-C6H3Cl2; 4d, Ar = 2,6-C6H3Cl2; 4e, Ar = 2,4,6-C6H2Cl3) and [(Ar)N=C(C10H6)C=N(Ar)](2)NiBr2 (5a, Ar = 2,3-C6H3Cl2; 5b, Ar = 2,4-C6H3Cl2; 5c, Ar = 2,5-C6H3Cl2), have been synthesized and investigated as precatalysts for ethylene polymerization. In the presence of modified methylaluminoxane (MMAO) as a cocatalyst, these complexes are highly effective catalysts for the oligomerization or polymerization of ethylene under mild conditions. The catalyst activity and the properties of the products were strongly affected by the aryl-substituents of the ligands used. Depending on the catalyst structure, it is possible to obtain the products ranging from linear alpha-olefins to high-molecular weight polyethylenes.

新型非肽类血管紧张素II受体拮抗剂设计合成及其生物活性研究

Ang II受体拮抗剂是作用于肾素-血管紧张素系统(RAS)的抗高血压药，因其抗高血压作用与较老的抗高血压药物作用相同，且更具有选择性，不良反应状况与安慰剂相似,而在高血压治疗中逐渐引起研究者重视，并成为目前增长最快的抗高血压药物。在许多AngII受体拮抗剂中四氮唑结构已成为固定基团，但四氮唑有许多合成及代谢弊端。因此，寻找其他合适的杂环酸性基团来替代四氮唑，在保持较高口服活性的同时克服相应缺陷，具有极其重要的意义。 本项目以四氮唑沙坦类药物为先导化合物，运用生物电子等排原理及拼合原理，根据计算机分子模拟研究结果，对其进行结构修饰和改造，首次将咪唑、氯代咪唑、三氮唑及咪唑啉替代四氮唑，并结合具有较高AngII受体拮抗活性的联苯并咪唑衍生物，设计并合成一系列含咪唑，咪唑啉，氯代咪唑及三氮唑衍生物的Ang II受体拮抗剂。 研究这一系列新型AngII受体拮抗剂的体内、体外抗高血压活性时，发现咪唑啉衍生物展示了与对照药物几乎相当的活性，而咪唑、氯代咪唑和三氮唑衍生物分别表现了较弱或者没有活性，这些研究对今后更进一步设计合成新的Ang II受体拮抗剂具有重要的指导意义，同时也为筛选抗高血压药物奠定良好的基础。 The angiotensin II receptor antagonists act on renin-angiotensin system (RAS), which are as effective as other types of anti-hypertensive drugs. Because even the more specific and comparable to placebo in terms of side effects, Ang II receptor antagonists cause a high attention and become the fastest growing anti-hypertension drugs. Most of such compounds share the biphenyltetrazole unit with the lead Losartan. However, there are many defects in tetrazole synthesis and vivo metabolism. Therefore, we felt quite encouraged to find some proper acidic heterocyclic groups which maintain the same oral bioavailability to replace the tetrazole. In the present paper, we applied the bioisostere and combination principle, in accordance with the results of computer modeling of molecular, to modify the lead structural of terazole in sartan compounds reported. We turned our attention to replace the tetrazole ring with imidazole rings, chloro-imidazole, imidazoline, traizole ring and combinated them with benzimidazoles derivatives which have antagonistic activity for angiotensin II to design and synthesize a series of Ang II receptor antagonists contaning imidazole ring, chloro-imidazole, imidazoline or traizole ring. In addition, activity tests in vivo and in vivo had shown that imidazoline derivatives display almost equivalent activity with the reference drug, but imidazole derivatives, chloro-imidazole, triazole derivatives were weak or non-performance of the hypotensive activity. We believe that the imidazoline derivative type Ang II receptor antagonists can build a foundation for the development of a novel series of anti-hypertensive drugs.

N,N,N ',N '-Tetramethylchloroformamidinium Chloride-Mediated Cyclizations of beta-Oxo Amides: Facile and Divergent One-Pot Synthesis of Substituted 2H-Pyrans, 4H-Pyrans and Pyridin-2(1H)-ones

An efficient and divergent one-pot synthesis of substituted 2H-pyrans, 4H-pyrans and pyridin-2(1H)-ones from beta-oxo amides based on the selection of the reaction conditions is reported. Mediated by N,N,N',N'-tetramethylchloroformamidinium chloride, beta-oxo amides underwent intermolecular cyclizations in the presence of triethylamine at room temperature to give substituted 2H-pyrans in high yields, which could be converted into substituted 4H-pyrans in the presence of sodium hydroxide in ethanol at room temperature, or into substituted pyridin-2(1H)-ones under reflux.

Efficient synthesis and utilization of phenyl-substituted heteroaromatic carboxylic acids as aryl diketo acid isosteres in the design of novel HIV-1 integrase inhibitors

Three new types of aryl diketo acid (ADK) isosteres were designed by conversion of the biologically labile 1,3-diketo unit into heteroaromatic motif such as isoxazole, isothiazole, or 1H-pyrazole to improve the physicochemical property of ADK-based HIV-1

The Anti-HIV Actions of 7-and 10-Substituted Camptothecins

Camptothecin (CPT), a traditional anti-tumor drug, has been shown to possess anti-HIV-1 activity. To increase the antiviral potency, the anti-HIV activities of two CPT derivatives, 10-hydroxy-CPT and 7-hydroxymethyl-CPT, were evaluated in vitro. The therapy index (TI) of CPT, 10-hydroxy-CPT and 7-hydroxymethyl-CPT against HIV-1(IIIB) in C8166 were 24.2, 4.2 and 198.1, and against clinical isolated strain HIV-1(KM018) in PBMC were 10.3, 3.5 and 66.0, respectively. While the TI of CPT, 10-hydroxy-CPT and 7-hydroxymethyl-CPT against HIV-2(CBL-20) were 34.5, 10.7 and 317.0, respectively, and the TI of the three compounds against HIV-2(ROD) showed the similar values. However, when the antiviral mechanisms were considered, we found there was no inhibition of 7-hydroxymethyl-CPT on viral cell-to-cell transmission, and was no inhibition on reverse transcriptase, protease or integrase in cell-free systems. 7-Hydroxymethyl-CPT showed no selective killing of chronically infected cells after 3 days of incubation. In conclusion, 7-hydroxymethyl-CPT showed more potent anti-HIV activity, while 10-hydroxy-CPT had less efficient activity, compared with the parent CPT. Though the antiviral mechanisms remain to be further elucidated; the modification of -OH residues at C-7 of CPT could enhance the antiviral activity, while of -OH residues at C-10 of CPT had decreased the antiviral activity, which provides the preliminary modification strategy for anti-viral activities enhancement of this compound.

Anti-HIV Actions of 7- and 10-Substituted Camptothecins (vol 15, pg 138, 2010)

The authors thank the anonymous reviewer for helpful comments on the early version of the manuscript. This work was financially supported by the earmarked fund for Modern Agro-industry Technology Research System, the Science Fund for Young Scholars in Sichuan Province (Grant No: ZQ 026-017), and the National 863 Project of China (No. 2008AA101001).

Synthesis of substituted pyridyl ureas by selenium dioxide-catalyzed carbonylation

A series of commercially useful substituted pyridyl ureas have been synthesized via selenium dioxide-catalyzed reductive carbortylation of substituted nitrobenzene or substituted nitropyridine with amine as co-reagent and carbon monoxide as carbonyl reagent instead of phosgene in one-pot reaction. The recycling reusability of catalyst was also tested. It was also found that selenium dioxide-catalyzed reductive carbonylation of nitroaromatics exhibited reaction-controlled phase-transfer phenomena of the catalyst. (C) 2003 Elsevier B.V. All rights reserved.

Effect of drying methods on the structure and catalytic combustion activity of Mn-substituted hexaaluminate catalysts

Conventional oven drying (COD) and supercritical drying (SCD) methods were applied to the preparation of Mn-substituted hexaaluminate (BaMnA(11)O(19-alpha)) catalysts. The effect of drying methods on phase composition, specific surface area, pore structure and combustion activity of the samples was investigated. The samples obtained by SCD have higher surface area, narrower pore size distribution, and higher combustion activity than those obtained by COD.

Preparation of Mn substituted La-hexaaluminate catalysts by using supercritical drying

LaMnxAl12-xO19 catalysts were prepared from NH4OH and metal nitrates solutions. Supercritical drying (SCD) and conventional oven drying (CD) methods were used to extract the water in the hydrogel. The effects of drying methods on properties of the catalysts were investigated by means of TEM, N-2-adsorption, thermogravimetry (TG)-differential thermal analysis (DTA) and X-ray diffraction. SCD method is beneficial to maintain high surface area and improving catalytic activity for methane combustion of the catalyst. The specific surface area and pore volume of LaMn1Al11O19 catalyst prepared by SCD method are 28 m(2)/g and 0.23 cm(3)/g, respectively, and the ignition of methane could be carried out at 450degreesC. However, those of the CD catalyst prepared from the same precursor are 15 m(2)/g, 0.11 cm(3)/g and 530 degreesC, respectively. Suitable Mn content (0 less than or equal to x less than or equal to 2) could promote the formation of LaMnAl11O19 hexaaluminate, while further addition of Mn (2 less than or equal to x less than or equal to 6) cause the formation of LaMnO3. (C) 2003 Elsevier B.V All rights reserved.