Direct Enantioselective Three‐Component Synthesis of Optically Active Propargylamines in Water

An enantioselective three‐component reaction of aldehydes, amines, and alkynes in water by using a bis(imidazoline)–Cu^I catalysts having a hydrophobic substituent and sodium dodecyl sulfate as a surfactant was developed. The reaction was applied to a broad range of aldehydes and alkynes to give optically active propargylamines with excellent yields (up to 99 %) and enantiomeric excesses (up to 99 % ee).     

Observation of Unusual Molecular Diffusion Behaviour below the Lower Critical Solution Temperature of Water/2‐Butoxyethanol Mixtures by using Fluorescence Correlation Spectroscopy

The effect of solute affinity on solute diffusion in binary liquids well below the lower critical solution temperature (LCST) was studied by using fluorescence correlation spectroscopy. We measured the hydrodynamic radii of a hydrophobic and an amphiphilic fluorescent dye under systematic variation of the relative molar fractions of water/2‐butoxyethanol and, for comparison, of water/methanol mixtures, which do not show phase separation. We found that the apparent hydrodynamic radius of the hydrophobic dye almost doubled in water/2‐butoxyethanol, whereas it remained largely unchanged for the amphiphilic dye and in water/methanol mixtures. Our results indicate that the translational diffusion of solutes is influenced by transient local solution structures, even at temperatures well below the LCST. We conclude that, even far below LCST, different solutes can experience different environments in binary liquid mixtures depending on both the solute and solvent properties, all of which impact their reactivity.     

Time-series observations of 210Po and 210Pb radioactivity in the western North Pacific

We carried out time-series observations of ²¹⁰Po and ²¹⁰Pb radioactivity in the western North Pacific Ocean. The sinking fluxes of particulate organic carbon (POC) in the mesopelagic zone were estimated from ²¹⁰Po radioactivity during several seasons in the subarctic and subtropical regions of the western North Pacific. The seasonal changes of POC fluxes at a depth of 400 m were larger in the subarctic region than in the subtropical region. The annual mean POC flux at a depth of 400 m was larger in the subarctic region (57 mgC m^?2 day^?1) than in the subtropical region (36 mgC m^?2 day^?1). The annual mean of the e-ratio (the ratio of POC flux to primary productivity) in the subarctic region (18 %) was about twice the e-ratio in the subtropical region (10 %). These results imply that the efficiency of the biological pump is larger in the subarctic region than in the subtropical region of the western North Pacific.     

Direct Asymmetric Mannich‐Type Reaction of α‐Isocyanoacetates with Ketimines using Cinchona Alkaloid/Copper(II) Catalysts

The enantioselective direct Mannich‐type reaction of ketimines with α‐isocyanoacetates has been developed. Excellent yields and enantioselectivity were observed for the reaction of various ketimines and α‐isocyanoacetates using cinchona alkaloid/Cu(OTf)₂ and a base. Both enantiomers of the products could be obtained by using pseudoenantiomeric chiral catalysts. This process offers an efficient route for the synthesis of α,β‐diamino acids.     

Catalytic Enantioselective Reaction of α‐Phenylthioacetonitriles with Imines Using Chiral Bis(imidazoline)–Palladium Catalysts

The catalytic enantioselective reaction of α‐phenylthioacetonitriles with imines has been developed. The reaction of various imines proceeds in good yields and diastereo‐ and enantioselectivities in the presence of chiral bis(imidazoline)–palladium catalysts. The obtained products can be converted into β‐aminonitrile or β‐aminoamide compounds without loss of enantiopurity.     

Highly Enantioselective Reactions of Configurationally Labile Epimeric Diamine Complexes of Lithiated S‐Benzyl Thiocarbamates

Substitution reactions that employ primary‐carbamoyl‐protected arylmethanethiols are described. The enantiodetermining step was found to occur in the post‐deprotonation step as a dynamic thermodynamic resolution with a chiral bis(oxazoline) ligand. The configurationally labile lithium complexes were trapped with various electrophiles to yield different substitution products in good to excellent yields and enantiomeric excesses. The absolute configurations of the substitution products were determined, and the stereochemical pathway of the substitution reaction was elucidated for different classes of electrophiles. The temperature‐dependent epimerization process was monitored by ¹H and ⁶Li NMR spectroscopy.     

Structure activity relationships of quinoxalin-2-one derivatives as platelet-derived growth factor-beta receptor (PDGFbeta R) inhibitors, derived from molecular modeling

We previously reported a quinoxalin-2-one compound (Compound 1) that had inhibitory activity equivalent to existing platelet-derived growth factor-beta receptor (PDGFbeta R) inhibitors. Lead optimization of Compound 1 to increase its activity and selectivity, using structural information regarding PDGFbeta R-ligand interactions, is urgently needed. Here we present models of the PDGFbeta R kinase domain complexed with quinoxalin-2-one derivatives. The models were constructed using comparative modeling, molecular dynamics (MD) and ligand docking. In particular, conformations derived from MD, and ligand binding site information presented by alpha-spheres in the pre-docking processing, allowed us to identify optimal protein structures for docking of target ligands. By carrying out molecular modeling and MD of PDGFbeta R in its inactive state, we obtained two structural models having good Compound 1 binding potentials. In order to distinguish the optimal candidate, we evaluated the structural activity relationships (SAR) between the ligand-binding free energies and inhibitory activity values (IC50 values) for available quinoxalin-2-one derivatives. Consequently, a final model with a high SAR was identified. This model included a molecular interaction between the hydrophobic pocket behind the ATP binding site and the substitution region of the quinoxalin-2-one derivatives. These findings should prove useful in lead optimization of quinoxalin-2-one derivatives as PDGFb R inhibitors.     

Nitrogen-directed ortho-arylation and -heteroarylation of aromatic rings catalyzed by ruthenium complexes

The ruthenium-catalyzed direct ortho-arylation reactions of 2-phenylpyridine and 2-aryloxazolines have been successfully expanded to the direct aryl-heteroaryl coupling reactions using heteroaryl bromides. The reaction mechanism involving the Ru^II/Ru^IV intermediates is proposed from the results of the stoichiometric reaction of a divalent ruthenacycle complex of 2-phenylpyridine with bromobenzene.     

Observation of intramolecular singlet and triplet excimers of tethered naphthalene moieties under the geometric constraints imposed by the host framework of zeolites

This paper describes the emission spectroscopic investigation of singlet and triplet excimers of tethered bisnaphthalene species at room temperature. 1,1'-Dinaphthylethane (DNE) and 1,1'-dinaphthylpropane (DNP) were incorporated into a 3-D network of a 1.3 nm diameter pseudo-spherical supercage of zeolites Y (with an entry aperture of 0.74 nm), and a 1-D channel of zeolite L with a 0.71 nm aperture. In the straight channel of zeolite L, DNP adopts a parallel-sandwich conformation as suggested by the observation of entirely excimeric fluorescence, while DNE can only enter the channel in an open form. As a result, incorporation of DNP into zeolite L exchanged with Tl(+) ions, which induce enhanced intersystem-crossing, allowed the observation of a broad and featureless phosphorescence spectrum that is ascribable to the triplet excimer of DNP. In contrast, an entirely monomeric phosphorescence is observed for DNE. Furthermore, we observed a monomeric phosphorescence spectrum for DNP in Tl(+)-exchanged zeolite Y, in which DNP was shown to assume its open conformation. Thus the parallel-sandwich structure is responsible for the triplet excimer of the bisnaphthalene species as well as for the singlet counterpart. The parallel-sandwich conformation of the triplet excimer of DNP immobilized by the host framework is significantly different from the previously proposed L-shaped configuration in solution. However, it is very similar to that of the triplet excimer of triple-tethered carbazolophane, as revealed quite recently by Ohkita's group (J. Phys. Chem. B, 2007, 111, 10905). Thus the present study helps tackle the long-term issue of triplet excimer through the use of zeolites.