Total synthesis of “(±)-senoxydene”

A triquinane having the structure proposed for senoxydene has been synthesized in a regio and stereoselective manner. However, the difference in their spectral data suggests that the structure of the natural senoxydene is incorrect and requires revision.     

Oxygen nonstoichiometry and cobalt valence in misfit-layered cobalt oxides

The hexagonal CoO₂ layer is the main building unit of the newly established category of misfit-layered and related oxides showing—as a general feature—excellent thermoelectric characteristics. Here we use high-quality samples of the three prototype phases, Na_0.77CoO_2+δ, Ca₃Co_3.95O_9+δ and (Bi,Pb)₂Sr₂Co₂O_8+δ, and apply both precise wet-chemical redox analysis techniques and thermogravimetric annealing experiments to approach the not-yet-addressed questions concerning oxygen nonstoichiometry and the valence of Co in these phases. In terms of the oxygen-stoichiometry tunability, substantial variation in the overall oxygen content upon reducing/oxidizing annealing is observed only for Ca₃Co_3.95O_9+δ. The valence of Co in all the samples is found to lie in a range of 3.0-3.3, being significantly lower than the commonly believed values of 3.3-3.5.     

Structures and Stabilities of Ternary Copper(II) Complexes with 3,5-Diiodo-L-tyrosinate. Weak Interactions Involving Iodo Groups

Structures and stabilities of the ternary copper(II) complexes Cu(DA)(AA), where AA refers to 3,5-diiodo-L-tyrosinate (I(2)tyr) or L-tyrosinate (Tyr) and DA refers to 1,10-phenanthroline (phen), 2,2'-bipyridine (bpy), 2-(aminomethyl)pyridine (ampy), histamine (hista), or ethylenediamine (en), have been investigated by potentiometric, spectroscopic, and X-ray diffraction methods. The stability constants have been determined by potentiometric titrations at 25 degrees C and ionic strength I = 0.1 M (KNO(3)). The equilibrium constants K for a hypothetical equilibrium, Cu(DA)(Ala) + Cu(en)(AA) Cu(DA)(AA) + Cu(en)(Ala) where Ala refers to L-alanine, have been calculated from the determined overall stability constants of the ternary complexes for estimating the stability enhancement due to the stacking interaction between the aromatic rings in Cu(DA)(AA). Large positive log K values have been obtained for the Cu(DA)(I(2)tyrOH) and Cu(DA)(I(2)tyrO(-)) systems (DA = phen or bpy, OH and O(-) refer to the protonated and deprotonated forms of the phenol moiety, respectively), indicating that the complexes are stabilized by effective stacking. Differences between the log K values for Cu(DA)(I(2)tyr) and Cu(DA)(Tyr) systems indicate that the iodine substituents greatly contribute to the stability enhancement. A distinct circular dichroism (CD) magnitude anomaly was also observed for the systems with large log K value, supporting the existence of the stacking interaction in Cu(DA)(AA). Two complexes, [Cu(bpy)(I(2)tyrO(-))(H(2)O)].2H(2)O (1) and [Cu(bpy)(I(2)tyrOH)(NO(3))].CH(3)OH (2), have been isolated as crystals and analyzed by the X-ray diffraction method. Both 1 and 2 crystallized in the orthorhombic space group P2(1)2(1)2(1) with four molecules in a unit cell of dimensions a = 9.2339(4), b = 16.9230(8), and c = 14.8584(5) ? for complex 1, and a = 11.2240(8), b = 11.715(1), and c = 17.966(2) ? for complex 2. The central Cu(II) ion for both complexes has a similar distorted five-coordinate square-pyramidal geometry with the equatorial positions occupied by the two nitrogen atoms of bpy and the nitrogen and oxygen atoms of I(2)tyr, and the apical position is occupied by a water molecule (for 1) or a nitrate ion (for 2). The opposite site to the axial water or nitrate oxygen atom is intramolecularly occupied by the side chain aromatic ring, which is approximately parallel to the copper coordination plane with the average spacing of 3.31 or 3.30 ? for complex 1 or 2, respectively, directly exhibiting the effective stacking interaction between the aromatic rings in the solid state. Distances between the iodine and one of the pyridine rings of bpy (3.79 ? for 1 and 3.56 ? for 2) are shorter than the van der Waals distance (3.85 ?), implying that the iodine substituent may be involved in a weak bonding interaction with the pyridine ring. Effects of the iodine substituents on the stacking interactions between the diiodophenol side ring and the coordinated aromatic diamine and their possible biological relevance have been discussed.     

A novel carbon skeletal trichothecane, tenuipesine A, isolated from an entomopathogenic fungus, Paecilomyces tenuipes

Tenuipesine A (1), a novel trichothecane with an unprecedented carbon-migrated skeleton that embodies of a cyclopropane ring, was isolated from cultivated fruiting bodies of Paecilomyces tenuipes (Isaria japonica), a popular entomopathogenic fungi employed in folk medicine and health foods in China, Korea, and Japan. The structure was determined on the basis of two-dimensional NMR data. Its stereochemistry was elucidated by spectroscopic data and the chemical transformation of the coexisting trichothecene, 4beta-acetoxy-12,13-epoxytrichothec-9-ene-3alpha,15-diol (2). [structure: see text]     

Polymerization initiated by an electron donor–acceptor complex. VI. Polymerization of methyl methacrylate initiated by a liquid SO2–nicotine complex and carbon tetrachloride

A kinetic study has been made of polymerization of methyl methacrylate initiated by an electron donor–acceptor complex of liquid SO₂ (electron acceptor) and nicotine (donor) in the presence of carbon tetrachloride. It is concluded that the polymerization proceeds through free-radical intermediates similar to the cases of liquid SO₂–pyridine and liquid SO₂–poly(2-vinylpyridine) complexes. The overall rate of polymerization is proportional to the square root of both liquid SO₂ and nicotine concentrations, and the values of k_p/k_t^½ under various polymerization conditions are in satisfactory agreement with the literature values. For the activation energy of initiation, 13.6 kcal/mole is estimated from the k_p/k_t^½ values obtained at temperatures ranging from 0 to 80°C.     

A reappraisal,based on (31)P NMR,of the direct coordination of a metal ion with the phosphoryl oxygen at the cleavage site of a hammerhead ribozyme

It has been generally accepted, on the basis of kinetic studies with phosphorothioate-containing substrates and analyses by NMR spectroscopy, that a divalent metal ion interacts directly with the pro-Rp oxygen at the cleavage site in reactions catalyzed by hammerhead ribozymes. However, results of our recent kinetic studies (Zhou, D.-M.; Kumar, P. K. R.; Zhang. L. H.; Taira, K. J. Am. Chem. Soc. 1996, 118, 8969-8970. Yoshinari, K.; Taira, K. Nucleic Acids Res. 2000, 28, 1730-1742) demonstrated that a Cd(2+) ion does not interact with the sulfur atom at the Rp position of the scissile phosphate (P1.1) in the ground state or in the transition state. Therefore, in the present study, we attempted to determine by (31)P NMR spectroscopy whether a Cd(2+) ion binds to the P1.1 phosphorothioate at the cleavage site in solution. In the case of the R32-S11S (ribozyme-substrate) complex, neither the Rp- nor the Sp-phosphorothioate signal from the S11S substrate at the cleavage site was perturbed (the change was less than 0.1 ppm) upon the addition of Cd(2+) ions (19 equiv) at pH 5.9 and 8.5. By contrast, we detected the significant perturbation of the P9 phosphorothioate signal from another known metal-binding site (the A9/G10.1 metal-binding motif). The Rp-phosphorothioate signal from A9/G10.1 was shifted by about 10 ppm in the higher field direction upon the addition of Cd(2+) ions. These observations support the results of our kinetic analysis and indicate that a Cd(2+) ion interacts with the sulfur atom of the phosphorothioate at the A9/G10.1 site (P9) but that a Cd(2+) ion does not interact with the sulfur atom at the Rp- or at the Sp-position of the scissile phosphate (P1.1) in the ground state.     

Stereoselective hydrogenation of conjugate diene directed by hydroxy group and asymmetric synthesis of deoxypolypropionate units

Optically active cyclic compounds carrying a conjugate diene and two hydroxy groups were prepared through the intramolecular Büchner reaction with a chiral tether and succeeding stereoselective conversion. Hydrogenation of the diene in the first step was not regioselective but resulted in three regioisomeric monoenes. Nevertheless, the final saturated product carrying two stereogenic centers could be obtained in 98% stereochemical purity on further hydrogenation under optimized conditions. The high stereoselectivity throughout the multiple pathways is attributable to the effective direction by the hydroxy group. Ring cleavage of the produced stereochemically pure seven-membered ring compounds successfully resulted in synthetic intermediates for deoxypolypropionates.     

Inverse relationship between increased apoptosis and decreased skin cancer in UV-irradiated CD1d-/- mice

We previously demonstrated that CD1d knockout mice were resistant to ultraviolet (UV)-induced immunosuppression. Because immune suppression is a critical factor in the development of UV-induced skin cancers, we investigated the response of wild type (WT) and CD1d-/- mice to UV carcinogenesis. We found that although 100% of WT mice developed skin tumors after 45 weeks of UV irradiation, only 60% of CD1d-/- mice developed skin tumors. To investigate the mechanisms involved in the resistance of CD1d-/- mice to UV-induced carcinogenesis, we determined the time course and kinetics of keratinocyte cell death after UV irradiation. After acute UV exposure, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL)-positive keratinocytes were eliminated from the skin of WT mice by 72 h post-UV, but they still persisted until 96 h in CD1d-/- mice. The kinetics of p53 protein expression closely followed the kinetics of apoptotic cell death. Chronic UV irradiation resulted in induction of a significantly higher number of apoptotic keratinocytes in CD1d-/- than WT mice. In addition, epidermis and dermis from chronically UV-irradiated CD1d-/- mice harbored significantly fewer p53 mutations than WT mice. These results indicate that the resistance of CD1d-/- mice to UV carcinogenesis may be due to increased cell death and elimination of keratinocytes and fibroblasts containing DNA damage and p53 mutations.     

Effective gauge theory and the effect of heavy quarks in Higgs boson decays

A general framework is given for evaluating the contributions of as yet undiscovered heavy quarks to the gluonic decay rate of the Weinberg-Salam type Higgs boson. Since the Yukawa coupling of the Higgs boson to a quark pair is proportional to the quark mass, loop graphs involving heavy quarks have a non-vanishing effect on the gluonic decay width of the Higgs boson. This effect of heavy quarks with massesM _j(j=t,...) much greater than the Higgs boson massm _H is calculated in an effective gauge theory. The effects of two different kinds of large logarithms, lnM _j ² /μ m _h ² /μ ² are separated and summed up by the renormalization group method. It is found that the higher order QCD corrections are large and that the gluonic contribution to the hadronic decay width is significant if there are more than three generations. The Higgs decay width can therefore be used to probe the number of generations of heavy quarks.