Internal delivery of soft chlorine and bromine atoms: stereoselective synthesis of (E)-beta-halogenovinyl(aryl)-lambda3-iodanes through domino lambda3-iodanation-1,4-halogen shift-fluorination of alkynes

4-(Difluoroiodo)toluene-induced domino lambda(3)-iodanation-1,4-halogen shift-ring enlargement-fluorination reaction of 5-halopentynes with a four-, five-, or six-membered carbocycle afforded the ring-expanded (E)-delta-fluoro-beta-halovinyl-lambda3-iodanes stereoselectively in high yields, probably via the intermediacy of five-membered halonium ions. Use of internal alkynes makes it possible to synthesize tetrasubstituted beta-halovinyl-lambda(3)-iodanes with defined stereochemistry.     

Raman study of the coordination structure of a rare Earth-acetate complex in water

The Raman spectra of aqueous LnCl(3) x 20H(2)O x CH3(C)OOLi (LnCl(3), rare earth chloride) solutions have been measured in the liquid state. The change of the Raman symmetric Ln(3+)-OH(2) stretching band (v(w)) showed that the decrease in the ionic radius of rare earth (Ln(3+)) ions induces a change in coordination number of the Ln(3+) ion. The two peaks at 946 and 958 cm(-1) of the C-C stretching band (v(CC)) of the acetate ion are assigned to the bidentate ligand and the polymeric chain structure, respectively. The coordination structure of the acetate ion to Ln(3+) ion prefers the bidentate ligand to the polymeric chain structure throughout the rare earth series. The fraction of the bidentate ligand increases with decreasing ionic radius of the Ln(3+) ion. On the basis of the analyses of the v(w) and v(CC) bands, the change in the coordination number of the Ln(3+) ion is mainly due to the structural change (from the polymeric chain structure to the bidentate ligand) of the Ln(3+)-acetate complex rather than a elimination of one water molecule. Our results show that the Ln(3+) ions tend to form the bidentate ligand rather than the divalent (M(2+)) ions.     

Density functional theory investigation of novel Eu(III) complexes with asymmetric bis(phosphine) oxides

Recently, we have developed novel Eu(III) complexes with three beta-diketonates and one asymmetric bis(phosphine) oxide whose light emission intensity is drastically increased. In this paper, one of these complexes is investigated by the density functional theory calculation. Sixteen isomers of this complex have been considered. The ratio of the existence for the most stable isomer (B1_1a) is found to be about 51%, and the sum of the ratio of the existence for the six most stable isomers (B1_1a, B1_3a, B1_8a, B1_2a, B1_1b, and B1_5a) is about 100%, assuming the Boltzmann distribution (T = 300 K). The coordination structures of the six most stable isomers in the ground states are similar, and we can expect asymmetric ligand fields for them, favorable for the efficient light emission. Vertical excitation energies and oscillator strengths for each isomer have been obtained by the time-dependent density functional theory. With the red-shift of the wavelength and the interpolation by Gaussian convolution, both the calculated absorption spectra for the most stable isomer B1_1a and the calculated absorption spectra for the ensemble average of the isomers are found to be similar to the experimental fluorescence excitation spectra. The efficiency of energy transfer from the triplet excited state to the Eu(III) ion is considered by calculating DeltaEET (difference between the adiabatic excitation energy of the complex for the lowest triplet state and the emission energy of the Eu(III) ion for 5D0 to 7F2). The characters for the lowest triplet states for the isomers are investigated by the spin density distributions of the triplet states.     

Synthesis of the entire carbon framework of the kedarcidin chromophore aglycon

In advanced studies directed toward the total synthesis of the kedarcidin chromophore, we have successfully achieved the late-stage installation of the nine-membered diyne ring in the presence of the highly functionalised ansamacrocyclic bridge.     

Methoxy- and fluorine-substituted analogs of O-1302: synthesis and in vitro binding affinity for the CB1 cannabinoid receptor

Methoxy and fluorine analogs substituted on the terminal carbon of the pentyl chain of N-(piperidinyl)-1-(2,4-dichlorophenyl)-4-methyl-5-(4-pentylphenyl)-1H-pyrazole-3-carboxamide (O-1302) were synthesized in a multi-step process from 5-phenyl-1-pentanol, which was based on the 1,5-diarylpyrazole core template of N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716) through condensation of the respective amine with pyrazole carboxylic acid, in order to develop tracers for medical imaging. Their potency for inhibiting the binding of the CB1 antagonist [(3)H]SR141716 was evaluated with the aim of developing positron emission tomography (PET) ligands for the cerebral cannabinoid CB1 receptor. These analogs bearing a piperidinyl carboxamide at the C(3) of the pyrazole ring exhibited affinities comparable to those of the CB1 reference antagonist SR141716, which warrants further investigation using the radiolabeled form for biological imaging studies. A morpholine ring substituted at the C(3) of the pyrazole ring resulted in a reduction of the CB1 affinity.     

Novel water-soluble sedative-hypnotic agents: isoindolin-1-one derivatives

We developed new intravenous sedative-hypnotic compounds with the isoindolin-1-one skeleton focusing on the water-soluble property and in vivo safety. We synthesized approximately 170 derivatives and evaluated their hypnotic effects by intravenous administration of the compounds to mice. A series of the 2-phenyl-3-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]isoindolin-1-one analogs, 3(-), 5(-), 27(-), and 47(-) [JM-1232(-)], showed potent sedative-hypnotic activity with good water solubility and a wide safety margin. The hypnotic doses (HD50s) of these 4 compounds when administered to mice were 2.35, 1.90, 2.17, and 3.12 mg/kg, respectively, and the lethal doses (LD50s) were 88.67, 64.69, >120, and >120 mg/kg, respectively. The therapeutic indexes (LD50/HD50) were 37.73, 34.05, >55.30, and >38.46, respectively. Among these compound, 47(-) [JM-1232(-)] is being considered as the most potential candidate for clinical trials in humans.     

Cowaniin, a C-glucosidic ellagitannin dimer linked through catechin from Cowania mexicana

A new complex tannin, cowaniin (1) was isolated from the leaves and stems of Cowania mexicana (Rosaceae), and its structure was characterized as novel C-glucosidic tannin dimer linked through (+)-catechin on the basis of spectral and chemical evidence. The inhibitory effect on activation of the Epstein-Barr virus early antigen was assessed for cowaniin. Six known polyphenols and related compounds, including a nitrile glucoside, purshianin, were also characterized.     

Simultaneous determination of amphoteric surfactants in detergents by capillary electrophoresis with indirect UV detection

A simple, rapid and simultaneous determination of four types of amphoteric surfactants, i.e., C8, C10, C12, C14, C16 and C18-homologues of alkyldimethylamine N-oxide (AO), alkylamidopropylamine N-oxide (APAO), alkylbetaine (Bt) and alkylamidopropylbetaine (APB), was performed by using capillary electrophoresis (CE) with indirect UV detection. To optimize the separation conditions, effects of pH of background solution (BGS), organic modifier and chromophore for indirect UV detection on the CE separation of the amphoteric compounds were investigated. Addition of 50% (v/v) acetonitrile to the BGS under a lower pH condition brought a good separation performance due to the suppression of micelle formation for the analytes and the adsorption onto the inner surface of the capillary. Under an optimal condition, the 24 amphoteric analytes were completely separated in a single run within 17min. The relative standard deviation of the migration time was ranging from 0.20 to 0.23% and the limit of detection values for AO, APAO, Bt and APB homologues were 10-20, 20, 20-50 and 50microg/mL, respectively. Furthermore, the developed method can provide a high resolution separation of the amphoteric surfactants in commercially available detergents and shampoo without any sample pretreatments.     

Molecular aggregates of partially fluorinated quaternary ammonium salt gemini surfactants

The size and shape of novel partially fluorinated gemini surfactant 1,2-bis[dimethyl-(3-perfluoroalkyl-2-hydroxypropyl)ammonium]ethane bromide (CnFC3-2-C3CnF, where n=4, 6, and 8) were investigated in aqueous solution by means of light scattering and transmission electron microscopy (TEM). The sizes of these molecular aggregates changed with increasing carbon number of the alkyl chain and concentration. For example, the apparent hydrodynamic radius by dynamic light scattering was 18 nm at a concentration of cmcx5 for n=4, 115 nm at the cmcx15 for n=6, and 62 nm at the cmcx30 for n=8, at 298.2 K. The shapes of CnFC3-2-C3CnF aggregates drastically changed with the alkyl chain length; the aggregates were mainly in the form of large or irregular small aggregates (n=4), string-like aggregates (n=6), and vesicles (n=8). The bromide-ion activity was measured using a bromide-ion-selective electrode to determine the degree of counterion binding to the aggregates. The degree of counterion binding to aggregate was very small compared with that in the typical hydrogenated gemini surfactants. These results indicated that the small curvature of large aggregates was not influenced by an electrostatic repulsion between the cationic head groups in the case of the bulky molecular volume of fluorinated gemini surfactants.