Chemical Bonding in Polarised Push-Pull Ethylenes.

1,1-Diamino-2,2-bis(triflyl)ethylenes with both twisted and planar structures around the partial "C=C" bond were synthesised. Bonding properties in these compounds were analysed by an experimental approach using high-resolution X-ray diffraction data treated with X-ray wavefunction refinement (XWR). In the twisted compound, a dominant contribution of the charge-separated resonance structure was revealed. On the contrary, the nearly planar compound still showed π-bonding character, however, with a considerable contribution of the charge-separated resonance structure.

The synthesis of optically active N-C axially chiral tetrahydroquinoline and its response to an acid-accelerated molecular rotor.

Optically active atropisomeric N-(2,5-di-tert-butylphenyl)-1,2,3,4-tetrahydroquinoline with an N-C chiral axis was prepared via a catalytic enantioselective reaction. The addition of methane sulfonic acid to this axially chiral quinoline dramatically lowered the barrier to rotation around the chiral axis.

2-(Pyridinium-1-yl)-1,1-bis(triflyl)ethanides: structural behaviour and availability as bis(triflyl)ethylating reagents.

Stable and easy-to-handle zwitterions containing carbanion and pyridinium moieties were synthesized, and their structural studies by both X-ray crystallography and theoretical methods revealed the stereoelectronic effect in the zwitterionic 'C(-)-C-N(+)' system.

[Development of new mixing method of Busulfex injection for the purpose of improvement of medical safety method: the prefilled syringe method].

Busulfex is a new type of busulfan which can be administered intravenously. Usually it is administered over 2 hours every 6 hours. Its injection should be finished within 8 hours after mixture with a saline, which may bring some troublesome in clinical practice. We, here, introduce the prefilled-syringe method; Busulfex is filled into an injection syringe made of polypropylene beforehand under a sterile condition, and mixed with a saline just before the administration at the bed side. To evaluate the safety of this method we studied the stability of busulfan solution in the syringe physically and chemically. The drug solution was made with the same ingredients as Busulfex, filled into a syringe, and stored at 4 degrees C until use. Then, the transparency of this solution was studied with spectroscopy and the concentration of busulfan was analyzed directly by HPLC. Busulfan solution stored in non-colored injection syringe at 4 degrees C was stable for up to 96 hours both physically and chemically. We concluded that prefilled-syringe method is ease and safe way to administer Busulfex on scheduled time.

Highly selective stereodivergent synthesis of separable amide rotamers, by using Pd chemistry, and their thermodynamic behavior.

By using Pd chemistry, a highly selective stereodivergent synthesis of separable amide rotamers was achieved. Allylation of 2,4,6-tri-tert-butylanilides using a pi-allyl-Pd catalyst gave N-allylated anilides with moderate-to-excellent Z-rotamer selectivity (Z/E = 3 to > 50). The Z-rotamer selectivity depends considerably on the substituent on the anilide substrates. On the other hand, the E rotamers of N-allylated 2,4,6-tri-tert-butylanilides were obtained with almost complete selectivity (E/Z > 50) through O-allylation of 2,4,6-tri-tert-butylanilides and the subsequent Pd(II)-catalyzed Claisen rearrangement of the resulting O-allyl imidate. The prepared anilide rotamers changed to equilibrium mixtures in which the E rotamer was the major isomer when heated in toluene.

Highly enantioselective synthesis of atropisomeric anilide derivatives through catalytic asymmetric N-arylation: conformational analysis and application to asymmetric enolate chemistry.

In the presence of (R)-DTBM-SEGPHOS-Pd(OAc)(2) catalyst, N-arylation (aromatic amination) of various o-tert-butylanilides with p-iodonitrobenzene proceeds with high enantioselectivity (88-96% ee) to give atropisomeric N-(p-nitrophenyl)anilides having an N-C chiral axis in good yields. Atropisomeric anilide products highly prefer to exist as the E-rotamer which has trans-disposed o-tert-butylphenyl group and carbonyl oxygen. The application of the present catalytic enantioselective N-arylation to an intramolecular version gives atropisomeric lactam derivatives with high optical purity (92-98% ee). The reaction of the lithium enolate prepared from the atropisomeric anilide and lactam products with various alkyl halides gives alpha-alkylated products with high diastereoselectivity (diastereomer ratio = 13:1 to 46:1).

Catalytic asymmetric synthesis of vicinal diamine derivatives through enantioselective N-allylation using chiral pi-allyl Pd-catalyst.

[reaction: see text] N-monoallylation of meso-vicinal diamine bistrisylamides using a chiral pi-allyl-Pd catalyst proceeded in an enantioselective manner (up to 90% ee) to give desymmetrization products in good yields. The product was converted to the known sigma-receptor agonist in short steps. In addition, the present catalytic asymmetric N-allylation was applied to kinetic resolution of racemic-diamide.

An automated analyzer for methylated arginines in rat plasma by high-performance liquid chromatography with post-column fluorescence reaction.

A fully automated analyzer for methylated L-arginine metabolites [N,N-dimethyl-L-arginine (ADMA), N-methylarginine (NMMA) and N,N'-dimethyl-L-arginine (SDMA)] by high-performance liquid chromatography with post-column fluorescence derivatization was developed. This system consists of an on-line extraction, a separation on a reversed phase ion-pair chromatograph, a post-column derivatization by o-phthaladehyde (OPA) and thiol reaction, and fluorescence detection. NMMA, ADMA and SDMA were separated in 40 min with isocratic elution by a combination of octanoate and cyclohexane carboxylate as ion-pair reagents. The eluate was monitored at 450 nm with excitation at 337 nm. The calibration curves for NMMA, ADMA and SDMA showed linearity over the range from 0.05 micromol l(-1) (0.5 pmol on column) to 5.0 micromol l(-1) (50 pmol on column). This method does not require any time-consuming pre-treatment and requires only 10 microl of plasma sample for assay.