Asymmetric syntheses of fused bicyclic compounds by conjugate additions of allylic organolithium species to activated olefins and subsequent cyclizations

[reaction: see text]. Addition of the configurationally stable organolithium species produced by enantioselective deprotonation of N-Boc-N-(p-methoxyphenyl) allylamines to alpha,beta-unsaturated carbonyl compounds affords 1,4-addition products in good yields with high diastereomeric and enantiomeric ratios. Further transformations of these compounds provide [3.3.0]-, [4.3.0]-, [5.3.0]-, and [5.4.0]-carbocycles and heterocycles with high stereoselectivities.     

Aldol condensations over reconstructed Mg-Al hydrotalcites: structure-activity relationships related to the rehydration method

Two different rehydration procedures in the liquid or gas phase have been applied to reconstruct mixed oxides derived from calcined hydrotalcite-like materials to be used as catalysts for aldol condensation reactions. The as-synthesized hydrotalcite, its decomposition product, as well as the reconstructed solids upon rehydration were characterized by XRD, N(2) adsorption, He pycnometry, FTIR, SEM, TEM, (27)Al MAS-NMR and CO(2)-TPD (TPD=temperature-programmed desorption). Compared to the Mg-Al mixed oxide rehydrated in the gas phase (HT-rg), that rehydrated in the liquid phase (HT-rl) exhibits a superior catalytic performance with respect to the aldol condensation of citral with ketones to yield pseudoionones and in the self-aldolization of acetone. The textural properties of HT-rl and HT-rg differ strongly and determine the catalytic behavior. A memory effect led to a higher degree of reconstruction of the lamellar structure when the mixed oxide was rehydrated in the gas phase rather than in the liquid phase, although liquid-phase rehydration under fast stirring produced a surface area that was 26 times greater. This contrasts to typical statements in the literature claiming a higher degree of reconstruction in the presence of large amounts of water in the medium. CO(2)-TPD shows that the number of OH(-) groups and their nature are very similar in HT-rg and HT-rl, and cannot explain the markedly different catalytic behavior. Accordingly, only a small fraction of the available basic sites in the rehydrated samples is active in liquid-phase aldol condensations. Our results support the model in which only basic sites near the edges of the hydrotalcite platelets are partaking in aldol reactions. Based on this, reconstructed materials with small crystallites (produced by exfoliation during mechanical stirring), that is, possessing a high external surface area, are beneficial in the reactions compared to larger crystals with a high degree of intraplatelet porosity.     

The rate of homolysis of adducts of peroxynitrite to the C=O double bond.

Nucleophilic addition of the peroxynitrite anion, ONOO(-), to the two prototypical carbonyl compounds, acetaldehyde and acetone, was investigated in the pH interval 7.4-14. The process is initiated by fast equilibration between the reactants and the corresponding tetrahedral adduct anion, the equilibrium being strongly shifted to the reactant side. The adduct anion also undergoes fast protonation by water and added buffers. Consequently, the rate of the bimolecular reaction between ONOO(-) and the carbonyl is strongly dependent on the pH and on the concentration of the buffer. The pK(a) of the carbonyl-ONOO adduct was estimated to be approximately 11.8 and approximately 12.3 for acetone and acetaldehyde, respectively. It is shown that both the anionic and the neutral adducts suffer fast homolysis along the weak O-O bond to yield free alkoxyl and nitrogen dioxide radicals. The yield of free radicals was determined to be about 15% with both carbonyl compounds at low and high pH, while the remainder collapses to molecular products in the solvent cage. The rate constants for the homolysis of the adducts vary from ca. 3 x 10(5) to ca. 5 x 10(6) s(-1), suggesting that they cannot act as oxidants in biological systems. This small variation around a mean value of about 10(6) s(-1) suggests that the O-O bond in the adduct is rather insensitive to its protonation state and to the nature of its carbonyl precursor. An overall reaction scheme was proposed, and all the corresponding rate constants were evaluated. Finally, thermokinetic considerations were employed to argue that the formation of dioxirane as an intermediate in the reaction of ONOO(-) with acetone is an unlikely process.     

Poly(dimethylsiloxane) microchip for precolumn reaction and micellar electrokinetic chromatography of biogenic amines

We have demonstrated that precolumn derivatization and capillary electrophoresis separation on a poly(dimethylsiloxane) (PDMS) microchip can be realized as efficient as those on glass microchips. In an optimized condition of micellar electrokinetic chromatography (MEKC), using 25 mM sodium borate buffer (pH 10.0) with 25 mM sodium dodecyl sulfate (SDS) and 5% v/v methanol, the electroosmotic flow in an oxidized PDMS microchip is stabilized within 3% for days. By employing a fluorometric derivatization with o-phthaldialdehyde (OPA) in an optimally designed reaction chamber, four most important biogenic amines occurring in foods, histamine, tyramine, putrescine, and tryptamine, are quantitatively determined in less than 1 min at the levels applicable to real samples. The migration behaviors of anionic OPA-derivatized biogenic amines under the MEKC conditions are analyzed, and it has been found that under our separation conditions, the electrophoretic mobility of the SDS micelles is significantly greater than those of the anions in the aqueous phase. The channel manifold in a PDMS substrate is fabricated using replica molding against a thick photoresist, SU-8, pattern generated by photolithography. The plate with the microchannel pattern is strongly, irreversibly bonded to another PDMS plate by using a new bonding technique, which employs surface oxidation by corona discharge generated from a cheap, handy source, Tesla coil.     

Improved expression by cytomegalovirus promoter/enhancer and behavior of vascular endothelial growth factor gene after myocardial injection of naked DNA

Direct injection of the vascular endothelial growth factor (VEGF) gene plasmid DNA into the myocardium was shown to induce development of new blood vessels to increase the circulation in the heart of patients with coronary artery diseases. However, such angiogenic gene therapy (via naked DNA) was limited by low level of gene expression. Furthermore, the temporal and spatial characteristics of VEGF gene transfer in the heart are not known. In this study, we demonstrated that a plasmid vector, containing the human cytomegalovirus immediate early (HCMV IE) promoter and enhancer, induces greater expression of gene in the rat heart monitored by gene fused to the chloramphenicol acetyl transferase (CAT) reporter, than four different viral and cellular promoters. Interestingly, expression of VEGF121 protein showed an earlier peak, a shorter duration, and a wider distribution than that of CAT only. Therefore, a plasmid vector with an HCMV IE promoter/enhancer provides clear advantages over other previously developed plasmids. Furthermore, expression profile of VEGF121 gene may provide useful information in the design of angiogenic gene therapy in the heart.     

Sphingosine mediates FTY720-induced apoptosis in LLC-PK1 cells

FTY720, a synthetic sphingoid base analog, was examined as a new sphingosine kinase inhibitor, which converts endogenous sphingosine into its phosphate form. With 20 microM of FTY720, sphingosine accumulated in the LLC-PK(1) cells in a time- and dose-dependent manner. The FTY720 treated cells showed a high concentration of fragmented DNA, a high caspase-3 like activity and TUNEL staining cells. It was also found that the sphingosine and sphinganine level increased in a time- and dose-dependent manner within 12 h after the FTY720 treatment. The sphingosine kinase activity was reduced by FTY720 as much as other sphingosine kinase inhibitors, N, N-dimethylsphingosine (DMS), dl-threo-dihydrosphingosine (DHS). The fragmented DNA content as a result of the 20 microM of FTY720 treatment and by 5 microM of the exogenously added BSA-sphingosine complex indicated typical apoptosis. Under similar conditions, the accumulated sphingosine concentration in all the cells was almost identical even though the sphingosine distribution inside the cells was somewhat different. These results indicate that the FTY720 induced apoptosis is associated with the inhibition of the sphingosine kinase activity and is strongly associated with the successive accumulation of sphingosine.     

Preparation of block copolymer vesicles in solution

Block copolymer vesicles can be prepared in solution from a variety of different amphiphilic systems. Polystyrene‐block‐poly(acrylic acid), polystyrene‐block‐poly(ethylene oxide), and many other block copolymer systems can produce vesicles of a wide range of sizes; those in the range of 100–1000 nm have been explored extensively. Different factors, such as the absolute and relative block lengths, the presence of additives (ions, homopolymers, and surfactants), the water content in the solvent mixture, the nature and composition of the solvent, the temperature, and the polydispersity of the hydrophilic block, provide control over the types of vesicles produced. Their high stability, resistance to many external stimuli, and ability to package both hydrophilic and hydrophobic compounds make them excellent candidates for use in the medical, pharmaceutical, and environmental fields. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 923–938, 2004     

Biomimetic oxidative transformations of pericine: partial synthesis of apparicine and valparicine, a new pentacyclic indole alkaloid from Kopsia

A new pentacyclic indole alkaloid of the pericine-type, valparicine, representing the first member of this sub-group, was obtained from a Malayan Kopsia species and the structure was established by spectroscopic analysis. A partial synthesis of valparicine and apparicine from pericine was carried out via the Potier-Polonovski reaction and the biogenetic implications are discussed.     

Simple syntheses, structural diversity, and Tishchenko reaction catalysis of neutral homoleptic rare earth(II or III) 3,5-di-tert-butylpyrazolates--the structures of

The homoleptic rare-earth pyrazolate complexes [Sc(tBu2pz)3], [Ln2(tBu2pz)6] (Ln = La, Nd, Sm, Lu), [Eu4(tBu2pz)8] and the mixed oxidation state species [Yb2(tBu2pz)5] (tBu2pz = 3,5-di-tert-butylpyrazolate) have been prepared by a simple reaction between the corresponding rare-earth metal and 3,5-di-tert-butylpyrazole, in the presence of mercury, at elevated temperatures. In addition, [Yb2(tBu2pz)6] was prepared by redox transmetallation/ligand exchange between ytterbium, diphenylmercury(II) and tBu2pzH in toluene, whilst the same reactants in toluene under different conditions or in diethyl ether gave [Yb2(tBu2pz)5]. The complexes of the trivalent lanthanoids display dimeric structures [Ln2(tBu2pz)6] (Ln = La, Nd, Yb, Lu) with chelating eta2-terminal and eta2:eta2-bridging pyrazolate coordination. The considerably smaller Sc3+ ion forms monomeric [Sc(tBu2pz)3] of putative D3h molecular symmetry, with pyrazolate ligands solely eta2-bonded. [Eu4(tBu2pz)8] is a structurally remarkable tetranuclear EuII complex with two types of europium centres in a linear array. The outer two are bonded to one terminal and two bridging pyrazolates, and the inner two are coordinated by four bridging ligands. Unprecedented mu-eta5:eta2 pyrazolate ligation is observed, with each outer Eu2+ sandwiched between two eta5-bonded pyrazolate groups, which are also eta2-linked to an inner Eu2+. The two inner Eu2+ ions are linked together by two equally occupied components of each of two symmetry related, disordered pyrazolate groups with one component eta4:eta2 bridging and one eta3:eta2 bridging. [La2(tBu2pz)6] has also been shown to be a Tishchenko reaction catalyst with several organic substrates.     

Electrochemical genosensing properties of gold nanoparticle–carbon nanotube hybrid

We have investigated the electrochemical genosensing properties of gold nanoparticle–carbon nanotube hybrid. Thiolated oligonucleotide probes and mercaptohexanol were self-assembled onto the Au–CNT hybrid. The hybridization events of target oligonucleotides are monitored using electrochemical impedance spectroscopy, cyclic voltammetry and a.c. voltammetry techniques. A redox-active mediator is used to detect the oxidation of guanine residues. The as-fabricated genosensor is able to differentiate between complementary and mismatched hybridizations, relying on the oxidation current of the guanine residues mediated via .