Chihiro Ueda

Regulation of the human PDZK1 expression by peroxisome proliferator-activated receptor alpha.

Although PDZK1 is a well‐known adaptor protein, the mechanisms for its role in transcriptional regulation are largely unknown. The peroxisome proliferator‐activated receptor alpha (PPARα) is a ligand‐activated transcription factor that plays an important role in the regulation of lipid homeostasis. Previously, we established a tetracycline‐regulated human cell line that can be induced to express PPARα and identified candidate target genes, one of which was PDZK1. In this study, we cloned and characterized the promoter region of the human pdzk1 gene and determined the PPAR response element. Finally, we demonstrate that endogenous PPARα regulates PDZK1 expression.

Intramolecular Wittig reaction of α,α'-dioxocycloalkylidenetributylphosphoranes: formation and trapping of cycloalkyn-2-ones with five- and six-membered rings

Reaction of the title phosphoranes with homophthalic anhydride or 1,3-diphenylisobenzofuran in the presence of Me3SiCl gave the corresponding Diels–Alder adducts, indicating the transient intermediacy of cycloalkyn-2-ones with five- and six-membered rings.

Anodic oxidation of carboxamides. Part II. Anodic oxidation and pyridination of N-methyl-4′-methoxybenzanilide in acetonitrile

Anodic oxidation of N-methyl-4′-methoxybenzanilide (N-methyl-MBA) was investigated by cyclic voltammetry end controlled potential electrolysis at a glassy-carbon electrode in acetonitrile- in the presence and absence of water or pyridine. In acetonitrile N-methyl-MBA showed a single anodic peak at 1.27 V versus the saturated calomel electrode with a peak height corresponding to that of a two-electron process. Added pyridine and/or water had no effect on the peak potential or peak height. On electrolysis of N-methyl-MBA in acetonitrile, p-benzoquinone, and N-methylbenzamide were mainly formed. Essentially the same results were obtained on electrolysis in the presence of added water. In the presence of excess of pyridine, electrolysis of N-methyl-MBA resulted in the formation of pyridinated N-methyl-MBA in which the pyridinium group was meta to the anilide nitrogen atom on the N-methylanisidine ring. The results were compared with those obtained on anodic oxidation of 4′-methoxybenzanilide.

Hydrolysis of α-cyanobenzylideneanilines. Part I. Kinetic studies in acidic media

The hydrolysis of α-cyanobenzylideneanilines was studied kinetically in aqueous sulphuric acid (H0–2 to –6), 40% aqueous acetonitrile (pH 3–0), and 60% aqueous dioxan (H0 1·5 to –2) at 25°. Benzoyl cyanide was demonstrated to be an intermediate. The rate of hydrolysis exhibited a maximum at H0ca.–1 to –2. The effect of substituents on the reaction rate and the Bunnett–Olsen ϕ values suggested that the hydration of the protonated substrate is rate determining on the less acidic side of the rate maximum and that the decomposition of the intermediate amino-alcohol is rate determining under more acidic conditions. It is suggested, from consideration of the shape of the acidity–rate profile, that aniline is expelled only from the dipolar form (or zwitterionic form) of the amino-alcohol intermediate, because the tendency for aniline to separate is weakened by the electronwithdrawing cyano-group.

Anodic oxidation of carboxamides. Part 3. The mechanism of anodic cyclization of N-methylcarbanilides

Anodic oxidation in methanol of N-methylcarbanilides with an alkoxy-group para to the nitrogen atom (I) gives the intramolecular cyclization products, N-methylbenzoxazolium perchlorates: no cyclization product is obtained in the electrolysis of the anilides in acetonitrile. The process of cyclization was investigated by cyclic voltammetry, controlled potential electrolysis, and open circuit relaxation experiments using an optically transparent glassy carbon electrode. In spectroelectrochemical experiments on 4′-methoxy-N-methylbenzanilides (Ib–d) in methanol, accumulation of a metastable intermediate has been demonstrated. A possible reaction sequence for the formation of the benzoxazolium salts is discussed.

Hydrolysis of α-cyanobenzylideneanilines. Part 2. Kinetic studies in basic media

The base-catalysed hydrolysis of α-cyanobenzylideneanilines (I) was studied in aqueous dioxan (40 and 50% v/v) at 30°C. The rate of hydrolysis was first-order with respect to hydroxide ion. The plot of the logarithm of second-order rate constants for (I) with substituents on the C-phenyl ring against the σ value was linear (ρ 2.10), whereas that for (I) with substituents on the N-phenyl ring was concave. These results were compared with those for the reaction of (I) with ethoxide ion, where similar substituent effects were observed. These results were interpreted in terms of a mechanism involving tetrahedral addition intermediate, where the attack of hydroxide ion on the substrate is probably rate-determining. The curved Hammett plot cannot be ascribed to a change in mechanism, but seems to result from some other factors.

Kinetics of the dehydration of N-(α-cyanobenzyl)-N-phenylhydroxylamines

The rate of dehydration of N-(α-cyanobenzyl)-N-phenylhydroxylamines (I) catalysed by triethylamine and tri-n-butylamine were measured in 95% ethanol at 25°. The triethylamine catalysed rate of dehydration of α-cyano-p-chlorobenzyl derivative (Ic) was linearly correlated with the ionization ratio of p-cyanophenol in the same medium. Hammett ρ values of 2.90 and 1.57 were obtained for C- and N-phenyl substituents, respectively. The primary deuterium isotope effect for the reaction of (Ic) was ca. 6. An irreversible E1cB mechanism is suggested for the reaction except for the α-cyano-p-dimethylamino-derivative (Ie). The large positive deviation of (Ie) from the Hammett plot and its smaller deuterium isotope effect (ca. 3) are explained in terms of a transition to an E2 mechanism.

Fabrication of a micro-macro composite electrode used for voltammetric determination of dopamine in the presence of ascorbic acid.

十分大きな面積(ca. 0.08cm2)を持ち,互いに極めて近接した二つの電極(マクロ電極)の間に,微小電極(直径25μm)が位置するように作製した複合電極においては,マクロ電極へ適当な電位を印加することによって,微小電極表面の溶液環境を制御できることが示された.アスコルビン酸(AA),ドーパミン(DA)共存系においては,マクロ電極を+0.40V (vs.Ag/AgCl)に印加することにより, AAとDAの酸化電位の差がわずか100mVであるにもかかわらず,微小電極表面からAAが選択的に除去された.この条件下で微小電極を作動電極として微分パルスボルタンメトリーを行った場合, 10mMのAA共存下0.5mM以上のDAの定量が可能であった.

Electrochemical oxidation of 2,2,6,6-tetramethylpiperidines in acetonitrile: mechanism of N-cyanomethylation

Electrochemical oxidation of 2,2,6,6-tetramethylpiperidine (1a), its 4-oxo derivative (1b), and 2,2,6,6-tetramethylmorpholine (1c) in deoxygenated acetonitrile gave the corresponding N-cyanomethylated products (2). The process was investigated by cyclic voltammetry, controlled-potential electrolysis, and electrolysis in the cavity of an e.s.r. spectrometer. The sequence of cyanomethylation is proposed to be as follows: one-electron transfer from (1) to generate the radical cation, [graphic omitted]H+˙(3); deprotonation of (3) to give the aminyl radical, [graphic omitted]: (4); hydrogen abstraction by (4) from the solvent to afford the cyanomethylene radical; cross-coupling of (4) with the solvent-derived radical. The generation of the radical (4) was confirmed by the e.s.r. experiments. The decay of the 4-oxopiperidinyl radical (4b) obeyed first-order kinetics and exhibited a large primary deuterium isotope effect in [2H3]acetonitrile, indicating that the hydrogen abstraction is rate-determining. The voltammetric behaviour of (1) in oxygen-saturated acetonitrile suggested that the aminyl radical (4) is oxidized at a potential more positive than is the starting amine (1).

N-cyanomethylation of 2,2,6,6-tetramethylpiperidines by anodic oxidation in acetonitrile

Anodic oxidation of 2,2,6,6-tetramethylpiperidine and its 4-oxo-derivative in deoxygenated acetonitrile resulted in the formation on N-cyanomethylated products.