Stereoselective synthesis of procyanidin B3-3-O-gallate and 3,3″-di-O-gallate, and their abilities as antioxidant and DNA polymerase inhibitor

A simple method for the synthesis of procyanidin B3 substituted with a galloyl group at the 3 and 3″ position is described. Condensation of a benzylated catechin-3-O-gallate electrophile with a nucleophile, catechin and catechin-3-O-gallate, proceeded smoothly and stereoselectively to afford the corresponding dimer gallates, procyanidin B3-3-O-gallate and procyanidin B3-3,3″-di-O-gallate, in good yields. Further, their antioxidant activities on UV-induced lipid peroxide formation, DPPH radical scavenging activity and inhibitory activity of DNA polymerase were also investigated. Among three procyanidin B3 congeners (procyanidin B3, 3-O-gallate and 3,3″-di-O-gallate), the 3,3″-di-O-gallate derivative showed the strongest antioxidant and radical scavenging activity. Interestingly, the 3-O-gallate derivative was the strongest inhibitor of mammalian DNA polymerase with IC₅₀ value of 0.26 μM, although it showed the weakest antioxidant and radical scavenging activity. It became apparent that the presence of a galloyl group at the C-3 position in the proanthocyanidin oligomer was very important for biological activity, however, the antioxidant activity of these compounds was not parallel to the DNA polymerase inhibitory activity.     

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.     

Carbonyl reduction with CaH2 and R3SiCl catalyzed by ZnCl2

Ketones and aldehydes were effectively reduced to the corresponding alcohols (or their silyl ethers) by the reaction with CaH₂ and R₃SiCl in the presence of a catalytic amount of ZnCl₂. In the absence of the carbonyl substrate, the reagent reduced R₃SiCl to the corresponding hydrosilane under mild reaction conditions.     

Methyl groups as probes for proteins and complexes in in-cell NMR experiments

Studying protein components of large intracellular complexes by in-cell NMR has so far been impossible because the backbone resonances are unobservable due to their slow tumbling rates. We describe a methodology that overcomes this difficulty through selective labeling of methyl groups, which possess more favorable relaxation behavior. Comparison of different in-cell labeling schemes with three different proteins, calmodulin, NmerA, and FKBP, shows that selective labeling with [(13)C]methyl groups on methionine and alanine provides excellent sensitivity with low background levels at very low costs.     

Crystal structures and topochemical polymerizations of 7,7,8,8-tetrakis(alkoxycarbonyl)quinodimethanes

Highly conjugated monomers, 7,7,8,8-tetrakis(alkoxycarbonyl)quinodimethanes (methoxy (1a), ethoxy (1b), isopropoxy (1c), benzyloxy (1d), chloroethoxy (1e), and bromoethoxy (1f)), were synthesized. Recrystallizations of 1a, 1c, 1e, and 1f yielded two crystal forms (prisms (1a-A) and needles (1a-B), needles (1c-A) and plates (1c-B), prisms (1e-A) and plates (1e-B), and prisms (1f-A) and needles (1f-B)), which have different molecular packing modes by X-ray crystal structure analysis, indicating that the crystals are polymorphic. In the photopolymerizations of these monomer crystals in the solid state, 1a-A, 1e-A, and 1f-A polymerized topochemically to give crystalline polymers. For their thermal polymerizations in the solid state, in addition to 1a-A, 1e-A, and 1f-A, 1e-B and 1f-B polymerized, but polymers formed from the 1e-B and 1f-B were amorphous. The packing of quinodimethane molecules in the crystals was defined by four kinds of parameters, stacking distance (d(s)), the distance between the reacting exomethylene carbon atoms (d(cc)), the angles formed between the stacking axis and longer axis of the monomer molecule (theta(1)), and the shorter axis of the monomer molecule (theta(2)), and then the polymerization reactivity of these quinodimethanes in the solid state was discussed on the basis of these parameters.     

Tensammetric determination of microgram amounts of vanadium by catalytic oxidation of o-aminophenol

A tensammetric method is proposed for the determination of microgram amounts of vanadium, based on catalysis of the oxidation of o-aminophenol with sodium chlorate in acidic solution (pH 2.0). The oxidation product gives a very sensitive tensammetric wave; under optimum conditions, the wave-height is proportional to the concentration of va vanadium. From 0.2 to 3.0 mug of vanadium can be determined in a final volume of 50 ml. Mo(VI), W(VI), Mn(VII), Ce(IV) and large amounts of Al(III) and Fe(III) cause positive errors, and Hg(II) and thiosulphate negative errors. Interference from Fe(III), Al(III) and Cu(II) can be eliminated by solvent with oxine at about pH 8.0.     

Synthesis of a novel bridged nucleoside bearing a fused-azetidine ring, 3′-amino-3′,4′-BNA monomer

A novel bridged nucleic acid monomer, 3′-amino-3′-deoxy-5-methyl-3′-N,4′-C-methyleneuridine, was successfully synthesized via a useful and convenient azetidine ring formation under Staudinger's conditions. A ¹H NMR experiment and a PM3 calculation revealed that the sugar moiety of the novel bridged nucleic acid monomer, 3′-amino-3′,4′-BNA, was restricted to S-type conformation.     

Reactions of 1,2‐dihydro‐4H‐3,1‐benzothiazine‐2,4‐dithiones (trithioisatoic anhydrides) with N‐substituted benzylamines and trialkyl phosphites

Reactions of 1,2‐dihydro‐4H‐3,1‐benzothiazine‐2,4‐dithiones (trithioisatoic anhydrides) 3 with N‐substi‐tuted benzylamines 9 gave 1,2‐dihydroquinazoline‐4‐thiones 10 , o‐thioureidodithiobenzoic acid 11 , o‐aminothiobenzamides 12 , 2‐amino‐3,1‐benzothiazine‐4‐thiones 13 , or quinazoline‐2,4‐dithiones 14 , depending on the kinds of amine and the reaction solvent. On the other hand, reaction of 3 with trialkyl phosphites afforded dialkyl (1,2‐dihydro‐2‐thioxo‐4H‐3,1‐benzothiazin‐4‐yl)phosphonates 18 .     

Stabilities in field electron emissions from noble‐metal covered W nano‐tips: apex structure dependence

We observed field emission microscopy (FEM) patterns of noble‐metal (NM) covered W nano‐tips with three different apex structures fabricated by field evaporation. Each of the three tips was terminated with a single atom, three atoms or ten atoms. We investigated the temporal changes in the FEM of these tips to discuss the stabilities in the spatial distributions of the field emission (FE) beams. The single‐atom tip showed two characteristics that were superior to the others. First, the beams emitted from the single‐atom tip were the most collimated among the three tips (the semi‐cone angle of 1.0° , FWHM). Second, adsorption of residual gas had little influence on FE from the single‐atom tip, while the other tips were easily contaminated even at ultra high vacuum, resulting in the emission fluctuation. Copyright © 2006 John Wiley & Sons, Ltd.     

Reverse permeation of sodium ions driven by pH difference across a liquid membrane: time dependencies of membrane resistance and membrane potential in a reverse permeation system

The diffusional flux of sodium ions across a liquid membrane was observed as a reverse permeation phenomenon: sodium ions were transported across the membrane against their own concentration difference. A supported liquid membrane having stearic acid as an ionic carrier was used. The internal aqueous phase contained NaCl and HCl and the external aqueous phase contained NaOH of the same initial concentration as NaCl in the internal aqueous phase. The reverse permeation occurred with a long time delay. During the delay, sodium ions flowed from the acidic to alkaline solution. The diffusion coefficient of sodium ion estimated from the flux equation taking into account the Donnan equilibrium at the interface was found to be much greater than that in the membrane solvent, 1-octanol. In the same membrane system as for the flux measurement, the membrane conductance and the membrane potential were measured as a function of time. The time dependence of the membrane potential in the presteady state showed a biphasic behavior. The initial rapid phase could be attributed to the change in the phase boundary potential and the subsequent slow step to the change in the diffusion potential within the membrane. Before the steady membrane potential had been reached, the reverse permeation of sodium ions against their own concentration difference was not observed. During the slow relaxation process of the membrane potential, the membrane resistance decreased to approach the steady state. Moreover, the oscillation of membrane potential abruptly started at a time in the slow step of the potential change and continued during the steady state. It was suggested that, at the presteady state, the increase in the amount of water in the membrane would drive a drastic change in the state of the liquid membrane in the filter pore, e.g. an inverted micellar structure making.