Evaluation of Aromatic Amination Catalyzed by Palladium on Carbon: A Practical Synthesis of Triarylamines

A heterogeneous palladium on carbon (Pd/C)‐catalyzed coupling between amines and aromatic halides including aromatic chlorides has been achieved using sodium tert‐butoxide (NaO‐t‐Bu) and 1,1′‐bis(diphenylphosphino)ferrocene (dppf) as a ligand in cyclopentyl methyl ether (CPME). The use of potassium tert‐butoxide (KO‐t‐Bu) in place of NaO‐t‐Bu brought about the benzyne‐mediated aromatic amination even without Pd/C and dppf, giving a mixture of regioisomers when 4‐substituted bromobenzenes were employed as the substrate. The combination of Pd/C, dppf, NaO‐t‐Bu could be utilized for the syntheses of a broad range of triarylamines by replacing CPME with mesitylene which can provide a higher reaction temperature. The Pd/C could be quantitatively recovered and reused until at least the fourth cycle without any loss in catalytic activity. The quite low leaching of palladium (<1.1%) was demonstrated by an inductively coupled plasma‐atomic emission spectrometric analysis.     

Structure-Based Design,Synthesis, and Biological Evaluation of Imidazo[4,5-b]pyridin-2-one-Based p38 MAP Kinase Inhibitors: Part 1

We identified a lead series of p38 mitogen-activated protein kinase inhibitors using a structure-based design strategy from high-throughput screening of hit compound 1 . X-ray crystallography of 1 with the kinase showed an infrequent flip of the peptide bond between Met109 and Gly110, which was considered to lead to high kinase selectivity. Our structure-based design strategy was to conduct scaffold transformation of 1 with maintenance of hydrogen bond interactions with the flipped hinge backbone of the enzyme. In accordance with this strategy, we focused on scaffold transformation to identify imidazo[4,5-b]pyridin-2-one derivatives as potent inhibitors of the p38 MAP kinase. Of the compounds evaluated, 21 was found to be a potent inhibitor of the p38 MAP kinase, lipopolysaccharide-induced tumor necrosis factor-α (TNF-α) production in human monocytic leukemia cells, and TNF-α-induced production of interleukin-8 in human whole blood cells. Herein we describe the discovery of potent and orally bioavailable imidazo[4,5-b]pyridin-2-one-based p38 MAP kinase inhibitors that suppressed cytokine production in a human whole blood cell-based assay.     

一株片栗内生真菌的分离鉴定及其次级代谢产物对癌细胞的抑制作用

本文采用组织分离法从片栗叶部分离获得一株内生真菌,通过28s r DNA序列测定和系统发育树分析对此菌株进行了鉴定。用PD培养基和YM培养基分别发酵培养此菌株,其次级代谢产物通过高效液相色谱(HPLC)和质谱(MS)进行了分析。在YM培养基条件下对此菌株大量培养,利用硅胶层析等手段对其次级代谢产物进行分离纯化,采用MTT法测定了次级代谢产物对癌细胞的毒性。结果表明,从片栗叶部分离得到的内生真菌鉴定为Eupenicillium sp.NF2_PD013。经HPLC和MS分析表明,此内生真菌的次级代谢产物在YM培养基条件下比在PD培养基条件下丰富且产量大。从YM培养基条件下的次级代谢产物中分离得到4个化合物,分别为geodin,dihydrogeodin,3’-chlorotrypacidin和monochlorosulochrin,4个化合物均含有氯元素。化合物geodin和3’-chlorotrypacidin对乳腺癌细胞MCF-7和肝癌细胞Hep G2都有明显的增殖抑制作用。     

Piecewise affine systems approach to control of biological networks

In terms of a piecewise affine system representation, which is a kind of hybrid system model, this article discusses a series of approaches to modelling, analysing and synthesizing a biological network such as a gene-regulatory network. First, the input assignment problem, the controllable state set problem (CSP) and the input trajectory generation problem are emphasized as control problems to be addressed for biological networks. Subsequently, after the modelling issue on biological networks developed in the systems and control community is briefly explained, the CSP is described in detail with reference to control of the quorum-sensing system in the pathogen Pseudomonas aeruginosa. Finally, an optimal control design method to the quorum-sensing system is proposed as a solution to the input trajectory generation problem.     

绿色设计的发展及其在日本大阪大学的应用

在介绍所参与研究项目设计的基础上,探讨了日本绿色设计的进展与应用。探索了生态村的可持续发展生活方式设计及其三维图形处理的应用,展示了市民的参与设计模式与虚拟现实技术在沟通交流上的功能,并希望藉此提供一种独特的绿色设计思路：自下南上,软件先行。     

Reaction mechanism of methane activation using non-equilibrium pulsed discharge at room temperature

The reaction mechanism of methane activation using non-equilibrium pulsed discharge was largely clarified from the emission spectroscopic study and experiments with higher hydrocarbons and some kinds of isotopes. The strong emission of atomic carbon and C₂ swan band system was observed as well as H Balmer series emission. This indicates that methane was highly dissociated into C and H by electron impact, which is consistent with the result of high C₂D₂ composition in produced acetylene when the mixture of CH₄ and D₂ was fed into discharge region. High electron energy contributed to produce atomic carbon directly from methane, and high electron density promoted the dehydrogenation from CH₃, CH₂ and CH to produce atomic carbon consecutively. The reason for the high selectivity to C₂H₂ was the high concentration of CH or C₂ formed from atomic carbon, and the repetition mechanism of decomposition and recombination among C, CH, C₂ and C₂H₂.     

Control of Oxygen Permeability in Alumina under Oxygen Potential Gradients at High Temperature by Dopant Configurations

The oxygen permeability of polycrystalline α‐alumina wafers, which served as models for alumina scales on alumina‐forming alloys, under steep oxygen potential gradients () was evaluated at 1873 K. Oxygen permeation occurred by the grain‐boundary (GB) diffusion of oxygen from the higher‐oxygen‐partial‐pressure () surface to the lower‐ surface, along with the simultaneous GB diffusion of aluminum in the opposite direction. The fluxes of oxygen and aluminum at the outflow side of the wafer were significantly larger than at the inflow side. Furthermore, Lu and Hf segregation at the GBs selectively reduced the mobility of oxygen and aluminum, respectively. A wafer with a bilayer structure, in which a Lu‐doped layer was exposed to a lower and an Hf‐doped layer was exposed to a higher , decreased the oxygen permeability. When the sign of was reversed, however, the oxygen permeability of the wafer was comparable to that of a nondoped wafer. Co‐doping with both Lu and Hf markedly increased the oxygen permeation, presumably because the Lu‐stabilized HfO₂ particles that were segregated at the GBs acted as extremely fast diffusion paths for oxygen through the large number of oxygen vacancies introduced by the solid solution of Lu in the particles.     

Hydration of phosphorylcholine groups attached to highly swollen polymer hydrogels studied by thermal analysis

Hydration of polymer chains plays a key role for determining the extent of protein adsorption on polymeric materials. Here we investigated the hydration of poly(2-methacryloyloxyethyl phosphorylcholine (MPC)) chains, which resist protein adsorption and following cell adhesion effectively. The hydration was compared with that of poly(methoxy oligo(ethylene glycol)-monomethacrylate (Me(EG)_nMA)) chains, which also have hydrophilic units. The poly(MPC) and poly(Me(EG)_nMA) hydrogels with equilibrium water contents (EWCs) in the range from 86 to 97 wt% were prepared. By differential scanning calorimetric measurements, water in both the hydrogels was classified into two states: freezable and nonfreezable water. The poly(MPC) hydrogels had larger nonfreezable water than the poly(Me(EG)_nMA) hydrogels even when their EWCs were similar, which indicated the higher hydrating ability of poly(MPC) chains. We suggested that the difference in the amount of nonfreezable water around polymer chains may influence the degree of protein adsorption resistance after contact with body fluid for a long period.     

Use of <Emphasis Type="Italic">Rhizopus delemar</Emphasis> lipase as compared with other lipases for determination of <Emphasis Type="Italic">sn</Emphasis>-2 fatty acids in triacylglycerol

The FA composition in the sn-2 position of TAG is routinely determined after porcine pancreatic lipase hydrolysis. However, the content of saturated FA increased when a pancreatic lipase preparation with higher specific activity was used. Lipase from Rhizopus delemar was selected as a potential replacement lipase for the following reasons: (i) The FA specificity is nearly equivalent in hydrolysis activity toward FA such as lauric, myristic, palmitic, palmitoleic, stearic, oleic, linoleic, and α-linolenic acids; and (ii) lipase from R. delemar hydrolyzes fatty acyl residues at the sn-1,3 positions of TAG. Acyl migration products were present at less than 0.8% in lipase hydrolysates containing 6–14% of sn-2 MAG. A reproducibility CV of less than 5% was obtained in a collaborative study in which the compositions of the main FA at the sn-2 position in olive oil were determined using lipase from R. delemar. This article was presented in part at the Biocatalysis Symposium, 94th AOCS Annual Meeting & Expo, Kansas City, Missouri, May 2003.