Solid-phase synthesis of liquid crystalline isoxazole library

Combinatorial library of isoxazoles was prepared by 1,3-dipolar cycloaddition on solid support. p-Cyano derivatives showed nematic and/or smectic A phases. A bilayer smectic phase for 2h is proposed by the combination of molecular mechanics calculation and X-ray diffraction experiment.     

Preparation and characterization of novel branched beta-cyclodextrins having beta-D-galactose residues on the non-reducing terminal of the side chains and their specific interactions with peanut (Arachis hypogaea) agglutinin

Six novel branched beta-cyclodextrins (betaCDs) having beta-D-galactose residues on the non-reducing terminal of the sugar side chains, namely 6(1),6(4)-di-O-(beta-D-galactosyl)-betaCD (10), 6-O-(beta-D-galactosyl)-betaCD (11), 6(1),6(4)-di-O-(beta-lactosyl)-betaCD (14), 6-O-(beta-lactosyl)-betaCD (15), 6(1),6(4)-di-O-(4'-O-beta-D-galactosyl-beta-lactosyl)-betaCD (18), and 6-O-(4'-O-beta-D-galactosyl-beta-lactosyl)-betaCD (19), were chemically synthesized using the trichloroacetimidate method. The reaction products were separated by HPLC on an amino column into dibranched and monobranched betaCDs. Their structures were confirmed by mass spectrometry (MS) and two-dimensional (2D) NMR spectroscopic analysis. To study the length of the sugar side chains attached to the CD ring, which leads to differences in the functions of the branched CDs, interactions of these compounds with peanut (Arachis hypogaea) agglutinin (PNA) were investigated using an optical biosensor and an inhibition assay based on hemagglutination. The results showed that all branched betaCDs interacted with PNA, and the binding affinity was 18>14>10 and 19>15>11 when the derivatives were compared on the basis of side chain length.     

The acid-catalyzed rearrangement of 1-N-allylindolines

Zinc chloride-catalyzed rearrangement of 1-N-allylindoline and 1-N-(2-methylallyl)indoline proceeds readily in refluxing xylene to give 7-allylindoline and 7-(2-methylallyl)indoline in 73% and 86% yields, respectively. The reaction of 1-N-2-butenylindoline and zinc chloride give rise to the mixture of 7-(1-methylallyl)indoline, 7-(cis- and trans-1-methyl-1-propenyl)indoline, and 7-(trans-2-butenyl)indoline. On the other hand, the similar reaction of 1-N-(3-methyl-2-butenyl)indoline with zinc chloride led to the formation of a mixture of 1,2,5,6-tetrahydro-4,4-dimethyl-4H-pyrrolo[3,2,1-ij]quinoline and 7-(3-methyl-2-butenyl)indoline.     

A novel rearrangement reaction in doubly charged ion mass spectra of acetophenone derivatives

A novel rearrangement reaction for a methyl group is found in doubly charged ion mass spectra of p-substituted acetophenone derivatives. The driving force for the reaction is discussed.     

Practical synthesis of 2'-deoxy-4'-thioribonucleosides: substrates for the synthesis of 4'-thioDNA

We report herein a practical synthesis of 4'-thiothymidine (15) and appropriately protected 2'-deoxy-4'-thiocytidine (16), -thioadenosine (27), and -thioguanosine (29) derivatives, substrates for the synthesis of 4'-thioDNA, from the corresponding 4'-thioribonucleosides. 2'-deoxy-4'-thiopyrimidine nucleosides were synthesized using a radical reaction of the corresponding 2'-alpha-bromo derivatives, which were prepared via 2,2'-O-anhydro derivatives. 2'-deoxy-4'-thiopurine nucleosides were synthesized using the same radical reaction of the corresponding 2'-beta-bromo derivatives.     

Synthesis of 2-chloro-1,1-difluoroallyl mesylates through novel rearrangement and CC bond formation by their Pd-catalyzed reaction with diethylzinc

Treatment of 2-chloro-3,3-difluoroprop-2-en-1-ol derivatives (2) with methanesulfonyl chloride in the presence of a base did not give the expected esters but 2-chloro-1,1-difluoroprop-2-enyl methanesulfonates (4) through a novel [3,3] sigmatropic rearrangement. Reaction of 4 with diethylzinc in the presence of tetrakis(triphenylphosphine) palladium gave 1-alkyl- or 1-aryl-2-chloro-3-fluoropenta-1,3-dienes in moderate to good yields through a CC bond formation followed by dehydrofluorination.     

Circular dichroism spectra of the inclusion complexes of phlorizin in cyclodextrins

Two aromatic rings of a phlorizin molecule form inclusion complexes with -CD and -CD. Induced circular dichroism spectra of these complexes have been measured to estimate the orientation of the two aromatic rings in the hydrophobic space of CDs. Apparent complex formation constants have been also estimated for each complex. It is concluded that phlorizin forms a stronger inclusion complex with -CD than with -CD.     

Kinetics of transient end-to-end contact of single-stranded DNAs

The formation of the pyrene (Py) dimer radical cation (Py(2)(*+)) was used to measure the kinetics of the intrastrand end-to-end contact rates of single-stranded DNAs (ssDNAs) in the 10 nanoseconds to the tens of microseconds time range. ssDNAs labeled with Py at both ends with the lengths of 3, 6, and 9 mer were synthesized, and the two-photon ionization method was employed to generate a Py(*+), which enables the measurements of the end-to-end contact rates from 10 ns. The formation rate of Py(2)(*+) depended on the length and the sequence of the ssDNAs, and about 1 order of magnitude faster rates were observed for the T-rich ssDNAs compared to those for the corresponding length of A-rich ssDNAs, showing that ssDNA made from adenines is much more rigid than that composed of thymidines. As for the T-rich ssDNAs, the formation of Py(2)(*+) attributed to the misfolded structures was also observed, which is consistent with the configurational diffusion model suggested by Ansari and co-workers.     

Synthetic studies on selective type 4 phosphodiesterase (PDE 4) inhibitors. 1. Structure-activity relationships and pharmacological evaluation of 1,8-naphthyridin-2(1H)-one derivatives

In order to develop novel and orally active phosphodiesterase (PDE) 4 inhibitors, random screening was performed using our chemical library to find YM-10335 possessing the 1,8-naphthyridin-2(1H)-one skeleton which is a completely different structure from rolipram. In this report, the syntheses and structure-activity relationships of the YM-10335 derivatives were described. Some compounds showed selective inhibitory activities for PDE 4 derived from human peripheral blood cells and no effect on the other PDE types (1, 2, 3, 5). The inhibition of the tumor necrosis factor-alpha (TNF-alpha) release in vitro and the carrageenan-induced pleurisy in rats were also described.     

The behaviour of dyes at oil/water interfaces

Summary The adsorption of ionic dyes, the builder effect, and the interaction between ionic dyes and surface active agents were investigated by using the electrocapillarity at oil/water interfaces. The oil phase was the solution of tetra-butylammonium chloride, sodium cetylsulphate, cetylpyridinium chloride or stearylamine in methylisobutylketone, and the water phase contained various dyes in addition to the inorganic electrolyte. The interfacial tension decreased over the anodic (or cathodic) polarization range, when anionic (or cationic) dyes were added to the water phase, thus indicating the dye adsorption at the interface. The interfacial excess of dye ions was found to increase linearly with the cubic roots of dye concentration and of ionic strength of the water phase. The counterion binding took place at the oil/water interface between anionic (or cationic) dyes and positive (or negative) head groups of surface active agent ions adsorbed at the interface. It was found that the equilibrium constants of binding between anionic dyes and cationic surface active agents at the oil/water interface were of the same order of magnitude as, and a little larger than, those obtained at the water bulk phase.

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Zusammenfassung An Öl-Wasser-Grenzflächen wurde die Adsorption ionischer Farbstoffe, die Füllerwirkung und die Wechselwirkung zwischen ionischen Farbstoffen und grenzflächenaktiven Verbindungen mit Hilfe der Elektrokapillarität untersucht. Die Ölphase bestand aus einer Lösung von Tetrabutylammoniumchlorid, Natriumcetylsulfat und Cetylpyridiniumchlorid oder Stearylamin in Methylisobutylketon. Die wässerige Phase enthielt verschiedene Farbstoffe und anorganische Elektrolyte. Die Grenzflächenspannung wurde durch anodische (bzw. kathodische) Polarisation erniedrigt, wenn anionischer (bzw. kationischer) Farbstoff zur Wasserphase gegeben wurde. Dies zeigt an, daß Farbstoff an der Grenzfläche adsorbiert wird. Die Grenzflächenkonzentration des Farbstoffions nimmt linear mit der Kubikwurzel der Farbstoffkonzentration und mit der Ionenstärke zu. Als Gegenionen für die anionischen (bzw. kationischen) Farbstoffe an der Grenzfläche wirken die positiven (bzw. negativen) Endgruppen der Tenside, die ebenfalls in der Grenzschicht adsorbiert sind. Die Gleichgewichtskonstanten für die Wechselwirkung zwischen den ionischen Farbstoffen und den grenzflächenaktiven Verbindungen sind an der Öl-Wasser-Grenzfläche von der gleichen Größenordnung bzw. geringfügig größer als in der wässerigen Volumenphase.

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With 12 figures and 2 tables