Search

A halide salt, hydroperoxide and AcOH catalyst system was applied to the oxidation of secondary benzylic alcohols. This simple system can be applied to a variety of secondary benzylic alcohols and scaled up for gram-scale preparation. High secondary benzylic alcohol selectivity of the present method is demonstrated in hydroxyketone synthesis. Based on several experimental results, a catalytic cycle for our oxidation is proposed.

Various experimental data have been supporting an idea that the conformation of A-site tRNA is different from that of P-site tRNA and have led to a new tRNA docking pair model, in which the highly conserved G18 and G19 of D-loop in A-site tRNA and C56 and C61 of T psi C-loop in P-site tRNA base pair exist along with the conventional base pairs of adjacent codon-anticodon interactions. This A-P tRNA pair model can be translocated to the P-E tRNA model without changing the conformation except the ACCA termini, keeping the position of the growing nascent polypeptide chain. On the other hand, it is noteworthy that C1378 of E. coli 16S rRNA cross-links to the 32 position on the anticodon loop of A-site tRNA in the pre-translocational state, and also to the same position of E-site tRNA in the post-translocational state, instead of the corresponding position of P-site tRNA. It resulted in a relationship between the A-P and P-E tRNA docking pair models in the pre- and post-translocational states, respectively, caused by a rotation with the angle of 25 degrees around the axis of rotation symmetry. Furthermore, nucleotide sequence analysis showed that CGAGC1107 of 16S rRNA is complementary with the conserved GT psi CG57 of tRNA. When it is combined with the P-E tRNA pair model, the crystallographically obtained L-shaped tRNA model fits both A-site codon with base pairings and the free T psi C-loop of P-site tRNA without base pairings. The base pairings between the GT psi CG57 of tRNA and the CGAGC1107 of 16S rRNA destabilize the bound aminoacyl-tRNA and result in a flow of discarding noncognate and near-cognate ternary complexes until cognate one arrives at the A-site codon. Recognition of a cognate ternary complex could occur, starting from breaking a hydrogen bond between N3 atom of U33 and O5' atom of A36 in the aminoacyl-tRNA, with base pairings of the codon-anticodon interactions, the conserved A 1394 in the 16S rRNA to the conserved U33 in the anticodon loop of the tRNA. The exposed U33 of the aminoacyl-tRNA is paired with A1394 in the recognition mode of A site, and finally passed to A1398 of A-site tRNA in the A-P tRNA pair model of the pre-translocational state. The exposure of U33 base at the A site is a key event in the mechanism of codon recognition.

Inter- and intramolecular Diels–Alder reactions of novel azadienes 2 and 3 are described. The dienes 2 and 3 react with electron-rich dienophiles, vinyl ethers 7a,b and p-methoxystyrene derivatives 7c,d to afford the corresponding cycloadducts 8 and 9, regioselectively. The azadienes 2 and 3 also undergo tandem transesterification and intramolecular cycloaddition with cinnamyl alcohols 13 in the presence of stannoxane catalyst 14 to give tetracyclic compounds 15 and 16 in one step. In a tandem process, the geometries of the dienophile components of 13 were transmitted into the cycloadducts 15 and 16.

In the presence of a chiral iridium catalyst, 1- and 3-substituted as well as 1,3-disubstituted isoquinolinium salts can be hydrogenated, giving the corresponding 1,2,3,4-tetrahydroisoquinolines in high enantiomeric excess.

The nBu4NI-catalyzed intramolecular cross-dehydrogenative coupling (CDC) reaction has been applied to the synthesis of 1H-indole derivatives. Intramolecular oxidative coupling of N-arylenamines proceeded in the presence of a catalytic amount of nBu4NI and tert-butyl hydroperoxide (TBHP) to afford the corresponding 1H-indole derivatives in good-to-excellent yields. A preliminary study of the synthesis of 3H-indole is also reported. This is a rare example of the nBu4NI-catalyzed C–C bond-forming CDC reaction.

In the presence of chiral Ir complexes and N-methyl-p-anisidine, 2-substituted quinoxalines undergo highly enantioselective hydrogenation to produce amines of type (II).

Photoinduced radical perfluoroalkylation of various simple electron-deficient olefins is achieved in the presence of an aqueous Na2S2O3 solution.

A general asymmetric hydrogenation of a wide range of 2-alkyl- and 2-aryl-substituted quinoxaline derivatives catalyzed by an iridium–difluorphos complex has been developed. Under mild reaction conditions, the corresponding biologically relevant 2-substituted-1,2,3,4-tetrahydroquinoxaline units were obtained in high yields and good to excellent enantioselectivities up to 95%. With a catalyst ratio of S/C = 1000 and on a gram scale, the catalytic activity of the Ir–difluorphos complex was maintained showing its potential value. Finally, we demonstrated the application of our process in the synthesis of compound (S)-9, which is an inhibitor of cholesteryl ester transfer protein (CETP).

The reaction of epoxides (I) with carbon dioxide is smoothly catalyzed by a tetranuclear zinc cluster—tetrabutylammonium iodide system to afford cyclic carbonates (III) in excellent yields.

TokyoGreen-methyleneoxy phosphate (I)(TG-mPhos) is the first fluorescence probe that shows selectivity for alkaline phosphatase (ALP) over protein tyrosine phosphatase and protein serine/threonine phosphatase.

The new Si-substituted fluorescence probe (Ia) possesses a high off/on activation ratio with a large red shift and a strong fluorescence intensity.

The identification of biomarkers is a promising approach for the diagnosis and effective therapy of cancer. In particular, disease proteomics is a potentially useful method for identifying such biomarkers. However, very few biomarker proteins for drug development have been discovered using this approach. The main difficulty is to efficiently select potential biomarkers from the many candidate proteins identified by the proteomics approach. To circumvent this problem, we have developed "antibody proteomics technology" that can screen for biomarker proteins by isolating antibodies against each candidate in a rapid and comprehensive manner. Here, we applied "antibody proteomics technology" to breast cancer-related biomarker discovery and evaluated the utility of this novel technology. Cell extracts derived from breast tumor cells (SKBR3) and normal cells (184A1) were analyzed by two-dimensional differential gel electrophoresis (2D-DIGE) to identify proteins over-expressed in the tumor cells. Candidate proteins were extracted from the gel pieces, immobilized onto a nitrocellulose membrane using a dot blot apparatus and then used as target antigens in scFv-phage enrichment and selection. Following this in vitro phage selection procedure, scFvs binding to 21 different over-expressed proteins in tumor cells were successfully isolated within several weeks. The expression profiles of the identified proteins were then determined by tissue microarray analysis using the scFv-phages. Consequently, we identified three breast tumor-specific proteins. Our data demonstrates the utility of an antibody proteomics system for discovering and validating tumor-related proteins in pharmaceutical proteomics. Currently, we are analyzing the functions of these proteins to use them as diagnostic markers or therapeutic targets.

Simple bromide salts can act as catalyst for the direct oxidative α-acetoxylation of Ketones.

ZrO2/Al2O3 composites with from 0% to 100% Al2O3 content were diffusion bonded at 12.5 MPa for 30 min in the temperature range 1450° to 1500°C. Under appropriate bonding conditions, a bonding strength greater than 1000 MPa was achievable between dissimilar materials with different thermal expansion coefficients.

The following species; superoxide (O2-.), hydrogen peroxide (H2O2), hydroxyl radical (.OH) and singlet oxygen (1O2), are generally called as reactive oxygen species (ROS). These species have been suggested to play important roles in various diseases caused by oxygen toxicity such as ischemia, carcinogenesis, inflammation, diabetes and aging. During the past two decades, considerable interests have been focused on chemical and biological research of ROS. We have also reported about the research results on ROS, which can be classified as following below; 1) chemical reactivities of O2-., 2) formation and toxicity of 1O2, 3) chemical reactivities of .OH, 4) enzyme mechanism of xanthine oxidase, 5) development of the compounds which induce the formation of O2-. and H2O2 in living cells and 6) development of superoxide dismutase mimics. These studies are reviewed from the standpoint of both chemical and biological interests.

(±)-1-epi-Magydardienediol, an intermediate for the synthesis of (±)-magydardienediol and (±)-magydartrienol, diterpenes isolated from Magydaris panacifolia(Vahl) Lange, has been synthesized stereoselectively from 3-methylcyclohex-2-enone in 12 steps via a sequential intra- and inter-molecular radical C–C bond-forming reaction.

Some modified α-CD on secondary hydroxyl side were prepared and conformation and configuration of them were studied by COSY, TOCY, and ROESY spectra. These spectra indicated that tosyl group of α-CD-2-OTs directed perpendicular to z-axis of α-CD-3-NH 2 and δ-CD-3-His had modified altrose residue with 1 C 4 conformation. Catalytic activity of α-CD-3-His was over 4 times larger than that of α-CD-6-His.

Absolute measurements of the photoionization and photodissociation cross sections of C2H2 have been made using continuum monochromatized synchrotron radiation in the 53–93 nm region. The absolute photoabsorption cross section and photoionization quantum yield of C2H2 have also been measured. The excitation spectra of C2(d 3Πg→a 3Πu), C2(C 1Πg→A 1Πu), CH(A 2Δ→X 2Π), and H(Lyman‐α) fluorescence have also been obtained. The obtained results have been compared with theoretical calculations. An unresolved problem of the spectral interpretation concentrated on the σ * and π* shape resonances has been clarified by the straightforward demonstration of the photoionization quantum yield. The ionizing and nonionizing decay processes of the superexcited C2H2 molecules have been discussed in view of the strong competition of autoionization and neutral dissociation. An overlapping nature of Rydberg states with the shape resonance is found to be important.

Stereoselectivity in the intermolecular trapping of the bicyclic radical intermediates from cyclization of 3-(1-ethoxy-2-haloethoxy)cyclohexenes with methyl acrylate was found to be affected remarkably by the conformation of the radical intermediates. The optimized conformers of 8-methoxy-7-oxabicyclo[4.3.0]non-2-yl radicals, models for the radical intermediates, were obtained by PM3 RHF molecular orbital calculations, and the stereoselectivity was analyzed in detail.

Nitric oxide (NO) reacts with H2O2 to produce a rise in potent luminol-dependent chemiluminescence under neutral pH conditions. We applied this reaction to the continuous detection of NO released from the rat isolated perfused kidney with simultaneous pressure changes. Acetylcholine increased NO release dose-dependently with the pressure reduction. An NO synthesis inhibitor, NG-monomethyl-L-arginine, abolished the release. This inhibition was reversed by the addition of L-arginine.

Diastereoselectivity in the addition of Grignard reagents (RMgX) to 3,4-O-isopropylidene-1-O-triphenylmethyl-L-glycero-2-tetrulose (1) and 1-O-benzoyl-3,4-O-isopropylidene-L-glycero-2-tetrulose (2) depended remarkably on R, X, the solvent, and the reaction temperature. In the reaction of 1 in diethyl ether at 0 °C and 2 in tetrahydrofuran were obtained (2R,3S)-adducts with moderate to high diastereoselectivity, while in the reaction of 2 in diethyl ether at −78 °C (2S,3S)-adducts were the major products. (2R)-2-Hydroxymethyl-2-nonyloxirane and (2S)-2-hydroxymethyl-2-tetradecyloxirane were synthesized.

Synthesis of 3-substituted 2-pyridinethiols was achieved by thiation of pyridine N-oxides with 4-methoxytoluene-α-thiol in the presence of diethylcarbamoyl chloride followed by cleavage of the resulting sulfides. The ease of substitution was shown to be affected by nucleophilicity of the N-oxide oxygen. Addition of zinc bromide to the reaction, a need for triethylamine, decreased most of the yield for thiation products but the formation of 3-methoxy-2-methoxybenzylthiopyridine was only improved. A plausible mechanism of the substitution, particularly β-thiation to the N-oxide function, is discussed compared with the regiochemistry observed in the reaction with diethoxyphosphoryl chloride instead of diethylcarbamoyl chloride. The debenzylation to pyridinethiol was also found to be dependent on the electron-density in the pyridine ring.

Gas-phase positive ion-molecule chemistry in phenylsilane, in phenylsilane/benzene-d 6 mixtures, and in several binary phenylsilane/hydrocarbon mixtures has been examined by the technique of Fourier transform ion cyclotron resonance spectrometry for the species C 6 H x Si + (x=5-8) formed by electron impact ionization of phenylsilane. Reaction pathways and rate constants have been determined for the reactions of the C 6 H x Si + ions with neutral phenylsilane and with neutral benzene-d 6 . Electron impact ionization of phenylsilane yields isomeric C 6 H 6 Si + (x=6-8) ions

3-(1,3-Butadienyl)cephalosporins 1 were prepared in high yields from readily available 3 via phoisphates (E)- 6 .

The photoextrusion of the SO-bridge of 7-thiabicyclo[2.2.1]hept-2-ene 7-oxides is discussed. An analysis of all the major by-products in the exemplary case of the photo reaction of 3a is given. The existence of intermediate dienes 4 has been established. Data on a comparative photoextrusion of an epithio-bridge of 7-thiabicyclo[2.2.1]-hept-2-ene (6) are provided.

Diels-Alder reactions of benzylidenecyanomethyl-1, 3-benzothiazoles and -1, 3-benzoxazoles 2a-f as 1-aza-1, 3-butadienes are described. The dienes 2, featuring the stabilized imine moieties by constituting heteroaromatic rings, react with both electron-deficient and electron-rich dienophiles 3a-c to give corresponding cycloadducts 4-6, regioselectively. The cycloadditions of the intramolecular systems 8a-d smoothly undergo via exo-transition state, stereoselectively affording polycyclic compounds 9a-d in good to excellent yields.

Diels–Alder reactions of benzylidene(cyano)methyl-1,3-benzothiazoles 2 and -1,3-benzoxazoles 3 as 1-azabuta-1,3-dienes are described. The dienes 2, 3, featuring stabilized imine moieties in the form of heteroaromatic rings, react with both electron-deficient and electron-rich dienophiles 7–9 to give corresponding cycloadducts 10–15 regioselectively. Cycloadditions of the intramolecular systems 18c, d and 19c, d proceed smoothly via an exo-transition state, stereoselectively affording polycyclic compounds 20c, d and 21c, d in good to excellent yields. X-Ray crystallographic studies of compounds 12e, 13a and 14b are also reported.

The asymmetric synthesis of a novel β3-adrenergic agonist FR165194 is described. The critical steps involve preparation of an optically active amine via stereoselective reduction of a chiral imine prepared from α-methylbenzylamine and synthesis of a chiral epoxide via the Sharpless asymmetric dihydroxylation.

Nitric oxide (NO), a multifaceted bioregulatory agent and an environmental pollutant, can effectively convert aromatic amines to the corresponding triazenes under aerobic conditions, but not under anaerobic conditions. Nucleic acid bases and nucleosides are also deaminated via hydrolysis of the diazonium ion products with exposure to aerobic NO solution. A peroxynitrite radical or nitrogen dioxide is suggested to be the ultimate reactive species.

The photochemical colour change from colourless to green of N-substituted 1-naphthylamines 1a–c in CH2Cl2 containing a haloform was found to be irreversible, although optically active 3-(1-naphthylamino)camphor 1a had been reported to exhibit reversible photochromism in CHCl3. Irradiation of N-(cis-4-tert-butylcyclohexyl)-1-naphthylamine 1b with CHI3 in hexane gave bis-1,1′-[4,4′(N-cis-4-tert-butylcyclohexyl)aminonaphthyl]methylium triiodide as green needles and N-(cis-4-tert-butylcyclohexyl)-1-naphthylamine hydroiodide as colourless crystals. A plausible pathway for the photochemical reaction of the N-substituted 1-naphthylamines with a haloform, which is initiated by electron-transfer from the nitrogen in the amines to the haloform followed by radical reactions which liberate hydrogen halide, is proposed.