gem-Difluorination of carbon–carbon triple bonds was conducted using Brønsted acids, such as Tf₂NH and TfOH, combined with Bu₄NBF₄ as the fluorine source. The electrochemical oxidation of a Bu₄NBF₄/CH₂Cl₂ solution containing alkyne substrates could also give the corresponding gem-difluorinated compounds (in-cell method). The ex-cell electrolysis method was also applicable for gem-difluorination of alkynes.

Abstract We wish to report a new synthetic approach for diphenylacetylene in which tetrachloroethylene was reacted with phenylboronic acid in the presence of Pd catalyst, followed by a workup procedure to provide the crude product, which was then allowed to react with n-butyllithium via the halogen lithium exchange of Cl atom and loss of Li and Cl atoms to afford the desired diphenylacetylene in good yield.

We recently reported novel purine-based CK2α inhibitors using the solvent ordering–based method as virtual screening. Among these, the X-ray crystal structure of a complex with CK2α was determined. The results...

This research aims to evaluate waste cotton and polyester as effective potential adsorbents for the removal of crystal violet (CV) from aqueous phases.

Abstract CCR4 is a major trafficking receptor for T-helper (Th) 2 cells and Th17 cells and is considered as a potential therapeutic target for atopic dermatitis (AD). The CCR4 ligands CCL17 and CCL22 have been reported to be upregulated in the skin lesions of AD patients. Of note, thymic stromal lymphopoietin (TSLP), a master regulator of the Th2 immune response, promotes the expression of CCL17 and CCL22 in AD skin lesions. Here, we investigated the role of CCR4 in an AD mouse model induced by MC903, a TSLP inducer. Topical application of MC903 to ear skin increased the expression of not only TSLP but also CCL17, CCL22, the Th2 cytokine IL-4, and the Th17 cytokine IL-17A. Consistently, MC903 induced AD-like skin lesions as shown by increased epidermal thickness; increased infiltration of eosinophils, mast cells, type 2 innate lymphoid cells, Th2 cells, and Th17 cells; and elevated serum levels of total IgE. We also found increased expansion of Th2 cells and Th17 cells in the regional lymph nodes (LNs) of AD mice. Compound 22, a CCR4 inhibitor, ameliorated AD-like skin lesions with reduction of Th2 cells and Th17 cells in the skin lesions and regional LNs. We further confirmed that compound 22 diminished the expansion of Th2 cells and Th17 cells in the coculture of CD11c+ dendritic cells (DCs) and CD4+ T cells derived from the regional LNs of AD mice. Collectively, CCR4 antagonists may exhibit anti-allergic effects by inhibiting both the recruitment and expansion of Th2 cells and Th17 cells in AD.

The electrochemical reduction conditions of the reaction of alkyl 2-chloroacetates in Bu₄NBr/DMF using a divided cell equipped with Pt electrodes to produce the corresponding cyclopropane derivatives in moderate yields were discovered. The reaction conditions were optimized, the scope and limitations, as well as scale-up reactions were investigated. The presented method for the electrochemical production of cyclopropane derivatives is an environmentally friendly and easy to perform synthetic procedure.

Cyanide is highly toxic to humans and the environment. It is very important to develop an on-site system for the quantitative analysis of cyanide with high sensitivity and reliability. In this study, we developed a cyanide detection system based on the reaction of vaporized cyanide on a glass-fiber filter soaked in a mixture of naphthalene-2,3-dicarboxaldehyde (NDA)-taurine-borate solution. Although the reaction product was stable for at least 3 days at room temperature, the reaction product on the strip was quickly quenched within a few minutes by direct irradiation with 405 nm light. To overcome this problem, we fabricated a simple device designed to detect the fluorescence intensity immediately after inserting a reaction strip into the device. The linearity of the calibration was obtained over a range of 1-100 µM of cyanide with good repeatability. The device is cost-effective (~ $300) and powered by batteries; therefore, it is suitable for the on-site determination of cyanide in crude samples.

A new cyanide ion sensor with a large Stokes shift and a good fluorescence quantum yield was prepared.

Atopic dermatitis is a chronic inflammatory skin disease involving T-helper (Th) 2 cells, eosinophils, and mast cells. Although CCR4 is a major chemokine receptor expressed on Th2 cells and regarded as a potential therapeutic target for allergic diseases, its role in atopic dermatitis remains unclear. Here, by using a hydrogel patch as a transcutaneous delivery device for ovalbumin (an antigen) and Staphylococcus aureus δ-toxin (a mast cell activator), we efficiently induced acute atopic dermatitis-like skin lesions in BALB/c mice, a strain prone to Th2 responses, which were characterized by increased numbers of eosinophils, mast cells, and CCR4-expressing Th2 cells in the skin lesions; elevated levels of total and ovalbumin-specific IgE in the sera; and increased expression of IL-4, IL-17A, IL-22, CCL17, CCL22, and CCR4 in the skin lesions. Of note, the same model was less efficient in C57BL/6 mice, a strain prone to Th1 responses. Using this atopic dermatitis model in BALB/c mice, we demonstrated that CCR4-deficiency or a CCR4 antagonist ameliorated the allergic responses. Collectively, these results demonstrate that CCR4 plays a pivotal role in skin allergic inflammation of BALB/c mice by recruiting CCR4-expressing Th2 cells and Th17 cells.

Hydroxychavicol (HC), which is obtained from the leaves of Piper betle LINN. (Piperaceae), inhibits xanthine oxidase (XO) with an IC50 value of 16.7 µM, making it more potent than the clinically used allopurinol (IC50=30.7 µM). Herein, a structure-activity relationship analysis of the polar part analogs of HC was conducted and an inhibitor was discovered with a potency 13 times that of HC. Kinetic studies have revealed that HC and its active analog inhibit XO in an uncompetitive manner. The binding structure prediction of these inhibitor molecules to the XO complex with xanthine suggested that both compounds (HC and its analog) could simultaneously form hydrogen bonds with xanthine and XO.

CCR4 is a major chemokine receptor expressed by Treg cells that downregulate immune responses. Here, we investigated the role of CCR4-mediated Treg cell recruitment in antigen-specific immune responses. CCR4-deficient mice immunized intramuscularly with ovalbumin (OVA) showed enhanced OVA-specific IgG responses. Furthermore, intramuscular administration of OVA induced the expression of MDC/CCL22, a ligand for CCR4, in macrophages of the muscle tissues, and enhanced the recruitment of CCR4+ Treg cells in wild-type mice, whereas this recruitment of Treg cells was severely impaired in CCR4-deficient mice. Furthermore, OVA-loaded dendritic cells (DCs) derived from the muscle injection site of CCR4-deficient mice had an upregulated expression of the DC activation marker CD40 and 86, and the lymphoid organ homing receptor CCR7 resulting in an increased number of migratory DCs in the regional lymph node. Compound 22, a CCR4 antagonist, also inhibited the recruitment of Treg cells to the muscle tissue, and further enhanced DC activation and homing to the regional lymph node. Consequently, Compound 22 enhanced OVA-specific IgG responses, and the expression levels of IL-4 and IFN-γ in CD4+ T cells and the levels of IFN-γ in CD8+ T cells. Finally, intramuscular administration of OVA and Compound 22 significantly inhibited the growth of OVA-expressing tumors. Collectively, CCR4 plays a pivotal role in Treg cell recruitment to the muscle tissue, and intramuscular administration of CCR4 antagonists may be a promising approach for enhancing vaccine efficacy.

ObjectivesTo avoid the chelate formation between levofloxacin (LVFX) and aluminium hydroxide in gastrointestinal tract, an ethoxycarbonyl 1-ethyl hemiacetal ester of levofloxacin (LVFX-EHE) was synthesised as a prodrug. MethodsThe effects of aluminium hydroxide on the bioavailability of LVFX following oral administration of LVFX-EHE were investigated in rats. Furthermore, the effects of aluminium hydroxide on small intestinal absorption of LVFX and LVFX-EHE when subjected to a hydrolysis experiment using in situ everted gut sac were investigated, and the minimal inhibitory concentrations (MICs) of LVFX and LVFX-EHE for various intestinal bacteria were measured. Key findingsWhen LVFX-EHE was co-administered with and without aluminium hydroxide, the AUC(0-4 h) values of LVFX hydrolysed from LVFX-EHE were similar to that of LVFX alone. In everted gut sac experiments, LVFX-EHE was efficiently absorbed even in the presence of aluminium ions after 1 h of incubation, whereas the absorption of LVFX decreased significantly in the presence of aluminium ions. MIC values of LVFX-EHE were far higher than LVFX. ConclusionsThis study suggests the benefit of ethoxycarbonyl 1-ethyl hemiacetal esterification of the carboxyl group of new quinolone as a prodrug which is able to avoid chelate formation.

CCR4 is a major chemokine receptor expressed by Treg cells and Th17 cells. While Treg cells are known to suppress antitumor immunity, Th17 cells have recently been shown to enhance the induction of antitumor cytotoxic T lymphocytes. Here, CCR4-deficient mice displayed enhanced tumor growth upon intradermal inoculation of B16-F10 melanoma cells. In CCR4-deficient mice, while IFN-γ+CD8+ effector T cells were decreased in tumor sites, IFN-γ+CD8+ T cells and Th17 cells were decreased in regional lymph nodes. In wild-type mice, CD4+IL-17A+ cells, which were identified as CCR4+CD44+ memory Th17, were found to be clustered around dendritic cells expressing MDC/CCL22, a ligand for CCR4, in regional lymph nodes. Compound 22, a CCR4 antagonist, also enhanced tumor growth and decreased Th17 cells in regional lymph nodes in tumor-bearing mice treated with Dacarbazine. In contrast, CCR6 deficiency did not affect the tumor growth and the numbers of Th17 cells in regional lymph nodes. These findings indicate that CCR4 is critically involved in regional lymph node DC-Th17 cell interactions that are necessary for Th17 cell-mediated induction of antitumor CD8+ effector T cells in mice bearing B16 melanoma.

Novel protein kinase CK2 inhibitors were identified using the solvent dipole ordering virtual screening method. A total of 26 compounds categorized in 15 distinct scaffold classes inhibited greater than 50% of enzyme activity at 50 mu M, and eight exhibited IC50 values less than 10 mu M. Most of the identified compounds are lead-like and dissimilar to known inhibitors. The crystal structures of two of the CK2 complexes revealed the high accuracy of the predicted binding modes. (C) 2015 Elsevier Masson SAS. All rights reserved.

Esterification of carboxylic acids with alkyl halides using electroreduction has been investigated. The reaction of carboxylic acids, such as benzoic acid, 3-phenylpropanoic acid, nonanoic acid, cinnamic acid, and 1-naphthoic acid, under electrochemical reduction conditions followed by the addition of alkyl halides afforded the corresponding esters in moderate to good yields. The reactions proceeded via the S(N)2 mechanism of the alkyl halide, with the carboxylate ion bearing the ammonium ion as the counter cation, which was generated and accumulated from the carboxylic acid. The generation of the carboxylate ion intermediate is essential, and it appears to have high reactivity because the counter cation of the carboxylate ion intermediate is an ammonium ion. (C) The Electrochemical Society of Japan, All rights reserved.

In this work, quaternary ammonium group-modified celluloses (QCs) were homogeneously synthesized by reacting cellulose with 3-chloro-2-hydroxypropyltrimethylammonium chloride in NaOH/urea solutions. The structure and solution properties of the QCs were characterized by elemental analysis, FT/IR, ¹H-NMR, and size exclusion chromatography. The results show that water-soluble QCs, with degree of substitution values, defined as the substitution of free hydroxyl groups of cellulose, 0.49– 0.72 and molecular weight 21–66 kDa could be obtained by optimizing the reaction time. The synthesized QCs were tested for protein separation as physically adsorbed coatings in capillary electrophoresis. Among the derivatives studied, quaternary ammonium cellulose showed rapid electroosmotic mobility and effective suppression of protein adsorption. The EOF can be manipulated for various applications by using QCs with different molecular weight. Because the reversed EOF can be obtained over a broad pH range, it is possible to separate basic, neutral, and acidic proteins under physiological conditions. Eight proteins; lysozyme, ribonuclease A, cytochrome C, α-chymotrypsinogen, α-lactalbumin, ovalbumin, transferrin, and myoglobin were baseline separated within 25 min by 25 mM sodium phosphate buffers (pH 7.0) containing 100 µg/mL QC.

A simple and convenient method has been developed for the synthesis of esters from the corresponding carboxylic acids and alkyl halides by using a stoichiometric amount of tetrabutylammonium fluoride (Bu4NF) as the base. The reaction of carboxylic acids and a Bu4NF/THF solution in DMF or THF as the solvent generates carboxylate ions in situ. The carboxylate ions thus generated and accumulated are highly reactive. They are then allowed to react with alkyl halides as the electrophiles, and afford the corresponding esters in moderate to good yields. The reaction without Bu4NF does not afford any product; therefore, Bu4NF seems to play an important role as the base in these reactions. A bulky countercation such as the tetrabutylammonium cation seems to increase the reactivity of the carboxylate ions in the solution phase.

We conducted team-based learning (TBL) with interdisciplinary lectures as a part of "Introduction to Pharmacy", divided among the pharmacy department's six pharmacist education curricula in the first semester. The interdisciplinary lecture is led by seven lecturers, each specializing in one area: cell biology, biochemistry, chemistry, public health pharmacology, pharmacokinetics, and clinical science. This lecture's purpose is to demonstrate to the students that all field subjects relate to each other and they must learn the basic science subjects to understand pharmaceutical sciences. The TBL contents have two themes, "cancer" and "aspirin", each of which had two lectures, each 90 minutes long and were conducted using TBL as expansive learning. On receiving knowledge of a wide range of fields in one lecture, a small number of students indicated that they were unable to understand the contents very well. However, in the questionnaire about TBL, many students reported "I have understood" and "I have enjoyed studying" using TBL, especially group readiness assessment test (GRAT). By incorporating TBL, they reported "increasing eagerness to learn pharmacy". Overall, students seem to have accepted TBL favorably, but they still find peer review difficult. We believe that their discomfort with peer review results from their unfamiliarity in evaluating others, and the time before the evaluation is short because TBL is conducted only twice.

The antimalarial activity of 1-aryl-3,3-dialkyltriazenes to Plasmodium berghei NK-65 in infected mice was evaluated at an intraperitoneal dose of 100 mg/kgbw. Some of these compounds were found to possess potent antimalarial activity. (c) 2007 Elsevier Ltd. All rights reserved.

Tetrahydrobenzotriazines, a novel class of heterocyclic compounds, were synthesized. Examination of their biological activities resulted in the discovery that some of them possess potent nematocidal activity. (c) 2006 Elsevier Ltd. All rights reserved.

The triazene compound {2,2'-[3-(4-methoxyphenyl)triaz-2-ene-1,1-diyl]diethanol} was utilized for the high sensitive and quantitative detection of ferric ion.

We are reporting on a new method of constructing dearomatized compounds from alpha-substituted aryltriazenes. Deprotonation occurs at C atom alpha to N3. Nucleophilic attack of generated anion at the ortho-position of aryl group forms a new carbon-carbon bond. A stereoselective reaction was observed when the substituents on the C alpha to N3 are tied together in either a pyrrolidine or a piperidine. The product of this reaction possessed an interesting dearomatized tetrahydrobenzotriazine framework. (c) 2006 Elsevier Ltd. All rights reserved.

(-)Plakolide A, an alpha-exomethylene-gamma-butyrolactone isolated from the marine sponge Plakortis sp., was synthesized starting from (R)-lactic acid by applying the chiral self-reproduction procedure.

A new approach to benzylamines using triazene compounds has been developed that is facilitated by the lithiation of aryltriazenes followed by treatment with an electrophile. The regioselectivity of the reaction can be controlled by means of the substituents in the aryl group. The reaction contains the following steps: intramolecular carbon-carbon bond formation involving lithiation of an alkyl group on a 3-nitrogen atom; a 1,2-proton shift; and the subsequent release of nitrogen gas. Through the use of a deuterated triazene, we were able to determine that the reaction proceeds through a 1,2-proton shift. (c) 2006 Elsevier Ltd. All rights reserved.

Molecular orbital calculations revealed that the introduction of a silyl group onto the 2-position of 1,3-dithiole caused significant decrease of the ionization potential and that 2-silyl-1,3-dithioles served as a pseudo π-electron system. The silyl group could also be utilized as a bridge for linking π-electron systems to achieve artificial stacking. These concepts led us to the design and synthesis of silyl-substituted 1,3-benzodithioles as candidates for new electron donors. The oxidation potential of monosilyl-substituted 1,3-benzodithiole was found to be significantly less positive than that of the parent 1,3-benzodithiole. The introduction of the second silyl group caused further decrease of the oxidation potential. Compounds composed of two 1,3-benzodithiole units linked by a silyl group were also synthesized. These showed comparable oxidation potentials to those of the corresponding monomeric compounds. The effect of stannyl-substitution onto the 2-position of 1,3-dithiole was found to be larger than that of silyl-substitution. The effects of silyl- and stannyl-substitution for related systems such as thioanisole and 1,3-dithiane were also studied.

The C-Si and C-Sn σ orbitals are higher in energy than C-H or C-C σ orbitals, and therefore can interact with neighboring π systems, non-bonding orbitals of heteroatoms, and other σ systems such as those of C-Si and C-Sn. Such interactions cause an increase of the HOMO level which in turn favors electron transfer. On the basis of this effect various types of redox selective reactions of organo-silicon and -tin compounds have been developed.

(-)-Malyngolide, an antibiotic isolated from a blue-green algae, was synthesized starting from (-)-quinic acid.

The introduction of tin on the carbon adjacent to the oxygen of aliphatic ethers results in significant decrease in the oxidation potentials. The effect of tin is much larger than that observed for silicon. Preparative electrochemical oxidation of α-alkoxystannanes results in selective cleavage of the carbon-tin-bond and introduction of a nucleophile such as an alcohol onto the carbon. © 1992.

【目的】近畿大学薬学部は近畿大学薬友会（同窓会）と協力し，卒業生を含む薬剤師が薬の専門家として高い水準を維持し続けることを目的として平成5年度から「生涯教育研修会」を開催している。研修会のプログラムは，前年度受講者のアンケートを元にその時々の変化に応じた課題をテーマとして取り上げているが，さらに受講生に有意義な研修会を目指して，多変量解析により詳細なアンケート分析を行う事とした。 【方法】学生を除く研修会受講者を対象に無記名にてアンケート調査を実施，その結果を集計し，多変量解析手法を用いて受講者の特徴などについて解析した。 【結果と考察】平成21年度のアンケートについて主成分分析を行った結果，「内容についての理解度」，「テーマに対する興味」，「新しく得た知識の量」，「業務に対して役立つ程度」の4項目の間には正の相関があった。また，積極的な方法で研修会を知った受講者ほど受講料を安いと感じ，受動的

【目的】近畿大学薬学部は近畿大学薬友会（同窓会）と協力し，卒業生を含む薬剤師が薬の専門家として高い水準を維持し続けることを目的とし，その時々の変化に応じた課題をテーマとして取り上げ，平成5年度から「生涯教育研修会」を開催している。研修会のプログラムは，前年度受講者のアンケートを元に作成している。このアンケート結果を分析することにより，受講生にとってさらに有意義な研修会を開催できると考え，今回解析を行った。 【方法】2009年9月から11月の間に3回開催した研修会の受講者合計1,846名を対象に無記名にてアンケート調査を実施，その結果を集計し，多変量解析手法を用いて受講者の特徴などについて解析した。 【結果と考察】合計391名からの回答があった。 アンケートの主成分分析を行った結果，薬学部ホームページや日本薬剤師研修会ホームページなど積極的な方法で研修会を知った受講者ほど受講料を安いと感じ，知人からの紹介，職場

我々が合成に初めて成功した新規複素環テトラヒドロベンゾトリアジンを有する化合物について、その生理活性の探索を種々行なったところ、その1つとして、殺線虫剤として有望な活性が見い出された。

我々が合成に初めて成功した新規複素環テトラヒドロベンゾトリアジンを有する化合物について、 その生理活性の探索を種々を行なったところ、 その 1 つとして、 除草剤として有望な活性が見い出された。

1 アリール 3， 3 ジアルキルトリアゼン化合物にキラルな配位子を共存させ、 反応を行ったところ、 生成物であるベンジルアミン誘導体に若干のエナンチオ選択性が見られた。 つまり分子間で不斉誘導が達成されたと考えられる。

1 アリール 3, 3 ジアルキルトリアゼン化合物に分子外及び分子内に不斉環境を導入し､ 立体選択的分子内炭素－炭素結合生成反応の検討を行った｡ その結果､ 生成するベンジルアミン誘導体のベンジル位炭素の立体化学の制御が若干ながら可能となった｡

1-アリール-3,3-ジアルキルトリアゼン化合物に塩基を作用させると、ベンジルアミン類が生成することを見出した。この反応は、トリアゼニル基のオルト位に水素を有する場合に限られる。実験および理論化学的手法を用いて、以下の様に反応機構を明らかにした。まず塩基により、3位の窒素上にあるアルキル基で脱プロトン化が起こり、カルバニオンが生成する。次に分子内で炭素-炭素結合生成反応が進行すると同時に、脱芳香族化が進行する。その後に、芳香環上で1,2-プロトンシフトが起こると同時に脱窒素が生じた結果、ベンジルアミン類の生成に至る。本反応において、トリアゼニル基に対してメタ位に置換基がある場合は、その置換基によって、生成するベンジルアミンの置換様式が異なった。メトキシ基やフルオロ基が置換した場合、オルト置換ベンジルアミン類が得られた。これは、置換基上にある孤立電子対が、塩基処理した直後のカルバニオンの対イオンに配位することにより、トリアゼニル基と置換基の間の位置で求核攻撃が生じたと考えている。また、置換基がトリメチルシリル基の場合、パラ置換体が得られたが、これはトリメチルシリル基の大きな空間支配の為に、カルバニオンとの立体反発が生じ、置換基とは遠ざかる位置、つまりトリメチルシリル基のパラ位で炭素-炭素結合生成反応が進行したと思われる。さらに、生成するベンジルアミン類のベンジル位炭素の不斉構築を検討した。まず、3位の窒素上のアルキル基上に不斉炭素を有するトリアゼン化合物を合成し、それを原料として用いた場合の、ジアステレオ選択的反応について試みた。期待した通り、良好な選択性で、反応が進行することが明らかとなった。次に、アキラルなトリアゼンを原料とし、分子外に不斉環境を構築した場合についても検討を行ったところ、僅かではあるが、エナンチオ選択性が見られた。