Photocycloaddition of 6-chloro-1,3-dimethyluracil to alkenes: synthesis of 1,2-dihydrocyclobuta[d]pyrimidine-4,6 (3H, 5H)-diones

The acetone-sensitized photocycloaddition of 6-chloro-1,3-dimethyluracil to alkenes affords directly 1,2-dihydrocyclobuta[$\text{d}$]pyrimidine-4,6 (3H, 5H)-diones $\text{via}$ 1-chloro-2,4-dimethyl-2,4-diazabichyclo[4.2.0]octa-3,5-diones.     

The decomposition of curvature netted hypersurfaces

We define the concept of a curvature netted hypersurface and investigate in what case the hypersurface is covered by a twisted product of spheres (or topological product of spheres). All hypersurfaces in a space form such that the number of mutually distinct principal curvatures is constant (i.e. each principal curvature has constant multiplicity) are curvature netted hypersurfaces. Also, we state some inductive constructions of the hypersurfaces, where we use the discussion related to the tube.     

Syntheses of polycyclic-1,4-dithiines and related heterocycles

Reactions of dihalogenoquinones or dihalogenoquinoxalines with thioamides gave the corresponding 1,4-dithiines in high yields. Many of polycyclic 1,4-dithiin derivatives can be synthesized by the reactions of dihalogenoheterocycles with thioamides, and they are useful as pigments and functional materials for electro-optical applications. Some of heteroaromatic-1,4-dithiins formed an intermolecular charge-transfer (CT) complex with a π-acceptor such as TCNQ, and they are useful as π-donors for CT complex.     

Reversible Dimerization and Polymerization of a Janus Diradical To Produce Labile C−C Bonds and Large Chromic Effects

Conducting polymers can be synthesized by irreversible diradical monomer polymerization. A reversible version of this reaction consisting of the formation/dissociation of σ‐dimers and σ‐polymers from a stable quinonoidal diradical precursor is described. The reaction reversibility is made by a quinonoidal molecule which changes its structure to an aromatic species by forming weak and long intermolecular C?C single bonds. The reaction provokes a giant chromic effect of about 2.5 eV. The two opposite but complementary quinonoidal and aromatic tautomers provide the Janus faces of the reactants and products which produces the observed chromic effect. A reaction mechanism is proposed to explain the variety of final products starting with structurally very similar reactants. These reversible reactions, covering an unusual regime of weak covalent supramolecular bonding, yield products which might be envisaged as novel molecular and polymeric soft matter phases.     

Intramolecular palladium-catalyzed allylic alkylation: enantio- and diastereoselective synthesis of [2.2.2] bicycles

Pd-catalyzed asymmetric allylic alkylation provides both enantio- and diastereoselectivity in formation of bicyclo [2.2.2] octan-2,3-diones and quinuclidin-2-ones, the latter potential precursors to quinine alkaloids. [reaction: see text]     

Stereoselective total synthesis of arenastatin A, a spongean cytotoxic depsipeptide

A highly stereoselective total synthesis of arenastatin A, an extremely potent cytotoxic cyclic depsipeptide from marine sponge, was developed. The desired 7,8-β-epoxide in arenastatin A was constructed by asymmetric sulfur ylide-mediated epoxidation in good yield and highly stereoselective manner.     

Protonation of the acidic residues in the transmembrane cation-binding sites of the ca(2+) pump

The ionization states of the acidic residues around the Ca2+-binding sites of sarcoplasmic reticulum Ca2+ ATPase are studied by continuum electrostatic calculations and all-atom molecular dynamics simulations with explicit solvent and phospholipids. The two methods consistently indicate that Glu58 and Glu908 are protonated at neutral pH. The Ca2+ coordination and the H-bonds formed by the protonation of Glu58 and Glu908 are stable in an MD simulation, whereas the H-bonds are disrupted and the Ca2+ coordination geometry is severely altered in another simulation treating these residues unprotonated. The results clearly indicate that the H-bonds formed by protonation of Glu58 and Glu908 provide extra stability for the Ca2+-binding sites of Ca2+ ATPase.     

One-milliliter wet-digestion for inductively coupled plasma mass spectrometry (ICP-MS): determination of platinum-DNA adducts in cells treated with platinum(II) complexes

Platinum (Pt)–DNA adducts formed by the anti-tumor agent cisplatin are recognized by the DNA mismatch repair (MMR) system. To investigate the involvement of MMR proteins including hMLH1 in the removal of these adducts, we developed a mL-scale wet-digestion method for inductively coupled plasma mass spectrometry (ICP-MS). The detection limit was 0.01 ng mL^–1 Pt, which corresponded to 2 pg Pt/g DNA when 10 g of DNA was used. The mean relative errors were 5.4% or better for a dynamic range of 0.01–10 ng mL^–1 Pt. DNA (~500 g) had no matrix effect. To improve the accuracy, DNA preparations were treated with ribonuclease and the apparent reduction in the concentration of Pt was corrected using cellular DNA levels, which were determined with Hoechst 33258. No significant differences were observed, in terms of the formation of Pt–DNA adducts or their removal over 6 h, between hMLH1-deficient HCT116 cells, a human colorectal cancer cell line, and hMLH1-complemented HCT116+ch3 cells (n=5; P>0.05), indicating that the hMLH1-dependent DNA repair systems contribute to neither the formation nor the removal of the adducts at detectable levels. In addition, approximately 19% of the adducts were removed within 6 h in both cell lines. A time course analysis (~24 h) suggested that the removal of cisplatin-generated Pt–DNA adducts follows first-order kinetics (t_1/2=32 h). The amount of Pt–DNA adduct formed by oxaliplatin in 1 h was 56% (ratio of means) of that generated by an equimolar concentration of cisplatin in HCT116. The proposed procedure could be useful for determining Pt–DNA adducts formed by Pt(II) complexes.     

Growth of HfO2 films using an alternate reaction of HfCl4 and O2 under atmospheric pressure

HfO₂ films were deposited onto a Si(1 0 0) substrate using an alternate reaction of HfCl₄ and O₂ under atmospheric pressure. Self-limiting growth of the HfO₂ was achieved in the range of the growth temperature above 873 K. The X-ray diffraction of the HfO₂ films showed a typical diffraction pattern assigned to the monoclinic polycrystalline phase. Residual chloride concentration in HfO₂ films were not higher than 0.1 at%. When the growth temperature was 973 K, the HfSiO_x is formed in HfO₂ film. This gives effective permittivity value of 9.6 for the HfO₂ film grown at 573 K.     

Orally active CCR5 antagonists as anti-HIV-1 agents 2: synthesis and biological activities of anilide derivatives containing a pyridine N-oxide moiety

In order to develop orally active CCR5 antagonists, we investigated 1-benzoxepine derivatives containing new polar substituents, such as phosphonate, phosphine oxide or pyridine N-oxide moieties, as replacements for the previously reported quaternary ammonium moiety. Among these compounds, the 2-(alpha-hydroxybenzyl)pyridine N-oxide 5e exhibited moderate CCR5 antagonistic activity and had an acceptable pharmacokinetic profile in rats. Subsequent chemical modification was performed and compound (S)-5f possessing the (S)-configuration hydroxy group was found to be more active than the (R)-isomer. Replacement of the 1-benzoxepine ring with a 4-methylphenyl group by a 1-benzazepine ring with a 4-[2-(butoxy)ethoxy]phenyl group enhanced the activity in the binding assay. In addition, introduction of a 3-trifluoromethyl group on the phenyl group of the anilide moiety led to greatly increased activity in the HIV-1 envelope-mediated membrane fusion assay. In particular, compound (S)-5s showed the most potent CCR5 antagonistic activity (IC(50)=7.2 nM) and inhibitory effect (IC(50)=5.4 nM) in the fusion assay, together with good pharmacokinetic properties in rats.