Highly E-selective and effective synthesis of antiarthritic drug candidate S-2474 using quinone methide derivatives.

We have developed an efficient and E-selective synthesis of an antiarthritic drug candidate (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide (S-2474; 1), in which alpha-methoxy-p-quinone methide is used as a key intermediate. alpha-Methoxy-p-quinone methide was revealed to be an equivalent to a p-hydroxy protected benzaldehyde. It reacts smoothly with alpha-sulfonyl carbanion to give 1,6-addition intermediates, which can be further processed to provide S-2474 directly in the presence of a base. This procedure gives S-2474 as an almost single isomer on the benzylidene double bond in excellent yield and thus is a very practical method adaptable to large-scale synthesis. The detailed mechanistic aspects are studied and discussed.     

Polymerization of DL-alanine NCA and L-alanine NCA

The polymerization of N-carboxy-DL -alanine anhydride and N-carboxy-L -alanine anhydride were carried out in various solvents such as acetonitrile, dimethyl sulfoxide (DMSO), and nitrobenzene. The x-ray diffraction diagram and the infrared spectra of the polymers of DL - and L -alanine were obtained. The polypeptides obtained in acetonitrile and in nitrobenzene were in the α conformation, and the conformation of polypeptide obtained in acetonitrile was not influenced by its molecular weight. The polypeptide obtained in DMSO was essentially in the β conformation. It was observed that the α and β forms of polyalanine were altered on treatment of the polymer with m-cresol, dichloroacetic acid, or formic acid.     

Higher order structure of proteins solubilized in AOT reverse micelles

The higher order structure of proteins solubilized in an bis(2-ethylhexyl) sulfosuccinate sodium (AOT) reverse micellar system was investigated. From circular dichroic (CD) measurement, CD spectra of cytochrome c, which is solubilized at the interface of reverse micelles, markedly changed on going from buffer solution to the reverse micellar solution, and the ellipticity values in the far- and near-UV regions decreased with decreasing the water content (W₀: molar ratio of water to AOT), indicating that the secondary and tertiary structures of cytochrome c changed with the water content. The ellipticity of ribonuclease A, which is solubilized in the center of micellar water pool, in the near-UV region was dependent on W₀ and became minimum when W₀ of ca. 8 while the ellipticity in the far-UV region was almost constant, indicating that the tertiary structure of ribonuclease A was affected by the water content, but the secondary structure was conserved. The degree of curvature of the micellar interface appears to influence the protein structure because the reverse micelle size is linearly proportional to the W₀ value. As evidence of this, when the micelle size was comparable to the protein's dimensions, the structures were more affected by the water content. Judging from the dependence of the factor influencing the protein structure on the protein species, the location of solubilized protein in reverse micelles is significantly related to whether the protein structure in the system is affected by the micellar interface. In the cases of cytochrome c and lysozyme, the ellipticity against W₀ was dependent on the AOT concentration. In contrast, ribonuclease A gave very similar ellipticity values whatever the AOT concentration. In the n-hexane micellar system, cytochrome c exhibited lower ellipticity values and ribonuclease A in the lower W₀ range (W₀ < ca. 8) higher ellipticity values. These results indicated that the interaction between the protein and the micellar interface is a dominant factor influencing the protein structure in reverse micelles, and that it is governed by the location of solubilized proteins and the state of the micellar interface.     

Reactivity of palladium nanoparticles supported on a microemulsion-based organogel network in supercritical carbon dioxide

Palladium (Pd) nanoparticles were prepared using the phase transfer method and coated with alkylamines as stabilizing agents stably dispersed in nonpolar solvents. Spherical Pd nanoparticles with an average diameter of 4 nm and a relatively narrow size distribution were obtained using hexylamine or dodecylamine, and they were successfully incorporated in microemulsion-based gelatin organogel (OG); also, an OG network containing Pd nanoparticles was prepared via drying. For the Mizoroki-Heck cross-coupling reaction of iodobenzene with methyl acrylate in supercritical carbon dioxide, the Pd nanoparticles in the OG network exhibited much higher reactivity than those in powder state. Preparation conditions of OG (e.g., gelatin concentration) affected the apparent reactivity of the supported Pd nanoparticles. The Pd nanoparticles in the OG network with high gelatin concentration were recycled with no appreciable change of reactivity. In contrast, the reactivity of the Pd nanoparticles with low gelatin concentration decreased during recycling.     

Extraction-spectrophotometric determination of traces of antimony in copper and lead metals and in lead-base alloy with pyrocatechol violet and tri-n-octylamine

A sensitive spectrophotometric method is described for the determination of antimony in copper and lead metals and in lead-base alloy. Optimal conditions have been established for the extraction and determination of antimony. Antimony (III) is extracted from a potassium iodide—sulfuric acid or a hydrobromic—sulfuric acid medium with toluene and converted to an antimony-pyrocatechol violet (PV) complex. The complex is then extracted with tri-n-octylamine (TOA) and the absorbance of the resulting ternary Sb(III)—PV-TOA complex is measured at 555 nm. As little as 0.5 p.p.m. of antimony in copper metal and 0.2 p.p.m. of antimony in lead metal and lead-base alloy can be determined.     

Thermodynamics of aqueous solutions of methyldiethanolamine and diisopropanolamine

The vapour–liquid equilibrium (VLE) of the systems of water + methyldiethanolamine (MDEA) and water + diisopropanolamine (DIPA) was measured at several temperatures with a static total pressure apparatus. The solid–liquid equilibrium (SLE) of the same systems was measured at low amine concentrations by means of two experimental methods: a visual method and a Differential Scanning Calorimeter (DSC). The activity coefficients of water + MDEA were modelled with the NRTL equations. The model parameters were regressed from VLE, SLE and excess enthalpy data from this work and from the literature. The model developed in this work was compared with models found in the literature. The NRTL equations were also used to model the activity coefficients of the system of water + DIPA. The model parameters were fitted from the VLE and SLE data measured in this work.     

Predictive elucidation of conformational characteristics and configurational properties of poly(1-methylphosphirane) and poly(1-phenylphosphirane) as a molecular design

Conformational characteristics and configurational properties of poly(1-methylphosphirane) (PMePP) and poly(1-phenylphosphirane) (PPhPP) have been predictively elucidated by the refined rotational isomeric state scheme coupled with ab initio molecular orbital and density functional calculations. The lone pair of the phosphorus atom adopts an sp hybrid orbital. Owing to the high s character (50%), the polyphosphiranes exhibit low proton (hydrogen) affinities, and hence the lone pair does not form any intramolecular attractive interactions with hydrogen. As the meso-diad probability varies from 0 (syndiotactic) to 1 (isotactic), the characteristic ratio of PMePP slightly increases from 6.7 to 7.4, whereas that of PPhPP considerably decreases from 38 to 7.3. The large dimension of syndiotactic PPhPP is chiefly due to π-π attractions formed between adjacent phenyl groups. The trivalent phosphorus atom may be bonded to heavy, noble, and transition metals but readily or gradually oxidized. The usefulness and necessity of the polyphosphiranes have been assessed.     

Preparation of axially chiral biphenyl diphosphine ligands and their application in asymmetric hydrogenation

Axially chiral biphenyldiphosphine ligands bearing diphenylphosphino group(s) and/or dicyclohexylphosphino group(s) were prepared in enantiomerically pure form starting from 2,6-dimethylnitrobenzene via 8 steps: iodination, reduction, methoxylation through diazotization, Ullmann coupling, bromination, phosphorylation, optical resolution, and silane reduction, and the obtained ligands were used in rhodium-catalyzed asymmetric hydrogenation.     

Anisotropic bulletlike emission of terminal ethynyl fragment ions: ionization of ethynylbenzene-d under intense femtosecond laser fields

The authors investigated Coulomb explosions of ethynylbenzenes under intense femtosecond laser fields. Deuteration on the edge of the triple bond gave information about specific fragment emissions and the contribution of hydrogen migration. Some fragments not resulting from migration were emitted in the direction of laser polarization. These were ethynyl fragment ions (D(+), CD(+), C(2)D(+), and C(3)D(+)). Although two bonds have to be cleaved to produce C(3)D(+), the rigid character of the triple bond was maintained in the Coulomb explosion process. In contrast, fragment ions, which are formed after single or double hydrogen migration, showed isotropic emissions with distinct kinetic energies. The character of the substituents has been found to hold even under strong laser light fields where violent fragmentation took place. The ethynyl parts were emitted like bullets from the molecular frame of ethynylbenzene despite the explosion into pieces of the main body of benzene ring.     

Enhancement of anthracene fragmentation by circularly polarized intense femtosecond laser pulse

The authors compared circularly and linearly polarized lights in the ionization and fragmentation of anthracene, using 800 nm femtosecond laser pulses at intensities of 10(13)-10(15) W cm-2. Singly and doubly charged intact molecular ions as well as numerous fragment ions were observed in the mass spectra, which were investigated as a function of laser intensity and polarization. At comparable intensities above the saturation threshold for complete ionization, the fragmentation pathways are enhanced with a circularly polarized field compared to a linearly polarized field. Resonant excitation of the molecular cation through the 2Au<--2Bg transition is proposed to be the initial step to ion fragmentation. The circularly polarized field interacts with a larger fraction of the randomly oriented molecules than the linearly polarized field, and this is considered to be the reason for the enhanced fragmentation brought about by circularly polarized light.