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[Image: see text] Therapeutic reactivation of the γ-globin genes for fetal hemoglobin (HbF) production is an attractive strategy for treating β-thalassemia and sickle cell disease. It was reported that genetic knockdown of the histone lysine methyltransferase EHMT2/1 (G9a/GLP) is sufficient to induce HbF production. The aim of the present work was to acquire a G9a/GLP inhibitor that induces HbF production sufficiently. It was revealed that tetrahydroazepine has versatility as a side chain in various skeletons. We ultimately obtained a promising aminoindole derivative (DS79932728), a potent and orally bioavailable G9a/GLP inhibitor that was found to induce γ-globin production in a phlebotomized cynomolgus monkey model. This work could facilitate the development of effective new approaches for treating β-thalassemia and sickle cell disease.

Post-translational modifications (PTMs) of proteins are a biological mechanism for reversibly controlling protein function. Synthetic protein modifications (SPMs) at specific canonical amino acids can mimic PTMs. However, reversible SPMs at hydrophobic amino acid residues in proteins are especially limited. Here, we report a tyrosine (Tyr)-selective SPM utilizing persistent iminoxyl radicals, which are readily generated from sterically hindered oximes via single-electron oxidation. The reactivity of iminoxyl radicals with Tyr was dependent on the steric and electronic demands of oximes; isopropyl methyl piperidinium oxime 1f formed stable adducts, whereas the reaction of tert-butyl methyl piperidinium oxime 1o was reversible. The difference in reversibility between 1f and 1o, differentiated only by one methyl group, is due to the stability of iminoxyl radicals, which is partly dictated by the bond dissociation energy of oxime O-H groups. The Tyr-selective modifications with 1f and 1o proceeded under physiologically relevant, mild conditions. Specifically, the stable Tyr-modification with 1f introduced functional small molecules, including an azobenzene photoswitch, to proteins. Moreover, masking critical Tyr residues by SPM with 1o, and subsequent deconjugation triggered by the treatment with a thiol, enabled on-demand control of protein functions. We applied this reversible Tyr modification with 1o to alter an enzymatic activity and the binding affinity of a monoclonal antibody with an antigen upon modification/deconjugation. The on-demand ON/OFF switch of protein functions through Tyr-selective and reversible covalent-bond formation will provide unique opportunities in biological research and therapeutics.

Hepcidin has emerged as the central regulatory molecule in systemic iron homeostasis. The inhibition of hepcidin may be a favorable strategy for the treatment of anemia of chronic disease. Here, we have reported the design, synthesis, and structure-activity relationships (SAR) of a series of 4-aminopyrimidine compounds as inhibitors of hepcidin production. The optimization study of 1 led to the design of a potent and bioavailable inhibitor of hepcidin production, 34 (DS42450411), which showed serum hepcidin-lowering effects in a mouse model of interleukin-6-induced acute inflammation.

A novel Tyr-selective protein bioconjugation using the water-soluble persistent iminoxyl radical is described. The conjugation proceeded with high Tyr-selectivity and short reaction time under biocompatible conditions (room temperature in buffered media under air). The stability of the conjugates was tunable depending on the steric hindrance of iminoxyl. The presence of sodium ascorbate and/or light irradiation promoted traceless deconjugation, restoring the native Tyr structure. The method is applied to the synthesis of a protein-dye conjugate and further derivatization to azobenzene-modified peptides.

The discovery and optimization of a novel series of G9a/GLP (EHMT2/1) inhibitors are described. Starting from known G9a/GLP inhibitor 5, efforts to explore the structure-activity relationship and optimize drug properties led to a novel compound 13, the side chain of which was converted to tetrahydroazepine. Compound 13 showed increased G9a/GLP inhibitory activity compared with compound 5. In addition, compound 13 exhibited improved human ether-a-go-go related gene (hERG) inhibitory activity over compound 5 and also improved pharmacokinetic profile in mice (oral bioavailability: 17 to 40%). Finally, the co-crystal structure of G9a in complex with compound 13 provides the basis for the further development of tetrahydroazepine-based G9a/GLP inhibitors.

The leaching behavior of arsenic (As), lead (Pb), nickel (Ni), iron (Fe), and manganese (Mn) was investigated from subsurface core sediment of marine and nonmarine depositional environments in central Kanto Plain, Japan. A four-step sequential extraction technique was adopted to determine the chemical speciation, potential mobility, and bioavailability of metals under natural conditions in variable depositional environments. In addition, a correlation of these properties with pore water and total metal content was carried out. The concentration of As in pore water was found to be 2&ndash, 3 times higher than the permissible limit (10 &micro, g/L) for drinking water and leachate in fluvial, transitional, and marine environments. The trend of potential mobile fractions of As, Pb, and Ni showed Fe&ndash, Mn oxide bound &gt, carbonate bound &gt, ion exchangeable bound &gt, water soluble in the fluvial environment. However, in the marine environment, it showed Fe&ndash, water soluble &gt, ion exchangeable bound for As. The leaching of As in this fluvial environment is due to the organic matter-mediated, reductive dissolution of Fe&ndash, Mn oxide bound, where Mn is the scavenger. The amount of total content of As and sulfur (S) in transitional sediment reflects an elevated level of leachate in pore water, which is controlled by S reduction. However, the leaching of As in marine sediment is controlled by pH and organic matter content.

Chemical modifications of native proteins can facilitate production of supernatural protein functions that are not easily accessible by complementary methods relying on genetic manipulations. However, accomplishing precise control over selectivity while maintaining structural integrity and homogeneity still represents a formidable challenge. Herein, we report a transition metal-free method for tryptophan-selective bioconjugation of proteins that is based on an organoradical and operates under ambient conditions. This method exhibits low levels of cross-reactivity and leaves higher-order structures of the protein and various functional groups therein unaffected. The strategy to target less abundant amino acids contributes to the formation of structurally homogeneous conjugates, which may even be suitable for protein crystallography. The absence of toxic metals and biochemically incompatible conditions allows a rapid functional modulation of native proteins such as antibodies and pathogenic aggregative proteins, and this method may thus easily find therapeutic applications.

Hepcidin has emerged as the central regulatory molecule of systemic iron homeostasis. Inhibition of hepcidin could be a strategy favorable to treating anemia of chronic disease (ACD). We report herein the synthesis and structure-activity relationships (SARs) of a series of indazole compounds as hepcidin production inhibitors. The optimization study of compound 1 led to a potent hepcidin production inhibitor 45, which showed serum hepcidin lowering effects in a mouse IL-6 induced acute inflammatory model.

In order to study convergence zones or discontinuous lines formed locally in the Taklimakan Desert, we analyzed available MODIS images onboad TERRA or AQUA satellite for ten cases: 29 March 2002, 14 April 2002; 2 January 2003; 21 April 2003; 26 March 2004; 28 April 2004; 30 January 2005; 25 June 2005; 3 December 2005; and 26 July 2006. We used weather maps published by the Japan Mete- orological Agency for the Asia and Pacific region at 500 hPa, 700 hPa and 850 hPa, at 00Z and 12Z to analyze the meteorological conditions occurring in each case. We estimated the positions of air streams, convergence zones or discontinuous lines between them, and thermal conditions on the maps and con- firmed the presence of cumulus and cumulonimbus clouds through satellite images in particular. After a review of previous studies, this paper introduced the results of the present study. Closed warm areas in the Taklimakan Desert and on the Tibetan Plateau and local convergence zones or discontinuous lines in the Taklimakan Desert were discussed together with their diurnal changes, using composite maps of the ten cases. Along the long axis of the desert the convergence zones or discontinuous lines normally extend 70-80 km in a west-east direction, but are suspected to exceed 100 km in extreme cases. On the other hand, the convergence zones or discontinuous lines extending in a north-south direction on the southern fringe of the desert have a length of 40-60 km. The closed warm areas show clear diurnal changes, but they were not detected at the 500 hPa level. An example of a clear convergence zone running in a north-south direction on 26 July 2006 was presented in detail with corresponding satellite images.

ASTERとLandsatによる計40シーンの衛星画像データを用い，塩類集積土壌域の空間分布とその時間変化を詳細に抽出できる手法について検討し，これをタリム盆地北部のオアシス周辺に適用した．まず，衛星画像データの反射スペクトル情報から，植生の活性度，表土の性質，および土壌の含水の程度に対する正規化指標SAVI，NDSI，NDWIを計算し，これらの大小関係を同時に表せるNDXI画像を提案した．2004年のASTERデ－タからNDXI画像を作成した結果，雨期では塩類集積土壌が雨水と混合するので塩類集積土壌の分布域は特定できないが，乾期（夏季）になれば植生の分布域・活性度の時間的変化は小さくなり，塩類集積土壌の分布が顕著になることがわかった．このNDXI画像によれば土壌水分量の大小によって塩類集積のメカニズムが異なることが示された．次に，LandsatとASTERのNDXI画像を最尤法によって分類した結果，固定砂丘の変化が最も大きく，面積が半減し，この多くが農地を含む植生域と塩類集積土壌の面積の単調増加に寄与していることがわかった．さらに，土壌サンプルに対して測定された反射スペクトルと塩分濃度から，反射率と塩分濃度との相関性に対する1次回帰式を求め，これを塩分指標（SI）と定義した．衛星画像にSIを適用した結果，2003年になると塩分濃度が全体的に増加し，塩類集積土壌の大部分は30 ppt以上の高濃度であり，流動砂域も塩分濃度が高い状態にあることが明らかになった．

Land cover change of the oases surrounding Taklimakan Desert in Xinjiang Uyghur in the past 40 years was examined by means of satellite images. From the results of the analysis of these images, the following have been explained. The farmland utilization ratio in average stands at 0.28 in the northern edge of Taklimakan Desert. In the meantime, the ratio stands at 0.13 in the southern edge, whereas 0.31 in the western edge. It is revealed that in the northern edge, area of the irrigation land is vast enough to be utilized. Small oases are much noticed generally in the southern edge, and accounted for usually less than 0.15 resulting in lowness in the utilization ratio of the farmland. However the smaller the value of the said ratio is, the higher the potential of the farmland development is. It is explained that the vegetation land is slightly expanded in the upper reaches of the river in the small oases in the northern edge, but the vegetation land is drastically changed to barren land in the lower reaches of the river. On the other hand, it is explained that the vegetation regions are being expanded year by year in the oases in the northern edge. Especially in Aksu, the farmland area was expanded accompanied with increase of the number of the development settlers.

A method for the on-site estimation of arsenic (As) contamination in soil by solid-phase extraction with a resin based on molecular recognition technology (SPE-MRT) and anodic stripping voltammetry (ASV) using a gold film microelectrode was developed. Optimized pretreatments were carried out as follows: 1 g of soil sample was taken and put into polypropylene test tube containing 33 mL 1 M hydrochloric acid solution, which was heated at 70 degree Celsius for 5 min using graphite block hot plate. As in the sample was extracted by shaking for 1 min using an automatic mini-shaker system. The extract was finally filtered through a 0.45 μm disk PTFE membrane filter. The extracted arsenic was electrodeposited on the gold film carbon microelectrode at −400 mV vs. Ag/AgCl for 1 min and the deposits were stripped at a rate of 5 mV/s to 580 mV vs. Ag/AgCl by using AnaLig® TE-3, Cu in soil extract was removed with 1 M hydrochloric acid for the determination of As. The method can eliminate Cu interference. The detection limit was 0.5 μg/L in soil extract. The results of voltammograms for As in the extracts from real soil samples were the same level as these obtained by a cross-check method using inductively coupled plasma mass spectroscopy (ICP-MS).

A method for the on-site estimation of lead contamination in soil by anodic stripping voltammetry using a mercury film microelectrode was developed. The optimized pretreatments were as follows: 1 g of soil sample was initially dried using a hot plate for 30 min with stirring; the sample was then extracted of lead with 33ml of a 1 mol·l-1 hydrochloric acid solution at 70°C for 15 min; the extract was finally filtered through a disk type glass fiber filter and a membrane filter. The lead extracted was electrodeposited on the microelectrode at -1.3V vs. Ag/AgCl for 2 min and the deposits were then stripped at a rate of 50 mV·s-1 to 0.15V vs. Ag/AgCl. By the application of a heated hydrochloric acid solution as an extracting solvent, the extraction time was greatly reduced compared with that of the official method based on soil contamination countermeasures law. The downsizing of the extraction was achieved using this method. The downsizing allowed the use of a portable mini-shaking machine and enabled the on-site extraction of lead from soil. The proposed method could be sufficiently applied to the on-site soil survey of lead contamination from bullets at a shooting range.

塩酸-過酸化水素水で分解した純銅試料溶液（pH約3.2）に5-スルホサリチル酸を添加して鉄（III）のみを選択的に錯形成させ，陰イオン交換樹脂でマトリックス銅と分離する高感度分析方法を開発した．カラム形状，樹脂量，試料溶液組成などの最適化により，定量精度を約2％ とすると100％ の鉄（III）吸着率が得られ，銅（II）と分離できた．陰イオン交換樹脂に吸着したスルホサリチル酸鉄（III）錯体は2 M硝酸10 mlで溶離した後，黒鉛炉原子吸光法で測定して鉄量を求めた．確立した最適操作条件下で20倍の濃縮効果が得られ，銅中0.16 μg g－1までの鉄が4％ 以内の相対標準偏差で定量可能である．有害試薬を用いない簡便な本法を用いて数種類の高純度銅試料を分析した結果は，精度，正確さ共に良好であり，オンライン分析への応用が期待できる．分析所要時間は約3時間であった．

高速液体クロマトグラフ/電気化学検出法によるエストロゲン及びビスフェノールAの一斉分析法を開発した．移動相には，0.07 mol l－1過塩素酸ナトリウムを含む45 vol％ アセトニトリル-55 vol％ 水の混合溶液（pH 2.7）を使用した．エストロゲン及びビスフェノールAの電解酸化はグラシーカーボン作用電極上，1.05 V vs. Ag/AgClで行った．ピーク面積で作成した検量線は10から1000 ng ml－1で原点を通る直線となり，100 ng ml－1での相対標準偏差（n＝5）は0.6から2％ であった．この分析法を下水処理場放流水及び河川水に応用した．共存するフミン物質からの妨害はメタノール水溶液を用いたクリーンアップ操作の適用で抑制することができた．S/N比から算出した検出限界は5 ng l－1であった．開発した方法は，誘導体化のような煩雑で時間を要する前処理が必要ないので，従来の分析法に比べて簡易迅速である．

We synthesized novel water-soluble and orally active taxane analogues, 7-deoxy-9beta-dihydro-9,10-O-acetal taxanes. Cytotoxicities of the synthetic compounds were greater than those of paclitaxel and docetaxel, especially against resistant cancer cell lines expressing P-glycoprotein. In addition, some compounds showed potent antitumor effects against B16 melanoma BL6 in vivo by both iv and po administration.

酸性溶液中, ジアゾ化-カップリング反応に基づくアゾ化合物を固体電極上に吸着するnMレベルの亜硝酸イオンの示差パルスカソーディックストリッピングボルタンメトリーを開発した. 0.4M塩酸 (pH約0.6) 中, 亜硝酸イオン溶液にスルファニルアミド溶液と1-ナフチルアミン溶液を加えてアゾ化合物を生成させ, 無電解 (開回路) でアゾ化合物をグラファイト電極上に濃縮した. 次いで50mV/sの速度で0.2から-0.2V vs. SCEまで電位を走査してボルタモグラムを記録し, ピーク高さから亜硝酸イオン濃度を求めた. -0.05V vs. SCE付近に良好な単一のピークが得られた. SN比を向上させるため空試験値の原因について検討した. また, 無電解前濃縮法の採用により, 共存元素の妨害は大いに抑制され, 選択性が向上した. 亜硝酸イオンの検量線は1.1～217nMで直線となり, 65nMでのRSD (n=5) は1.1%, 前濃縮時間5分間での検出限界は0.15nMであった. 取り扱いが容易な固体電極を用いた本法は, 亜硝酸イオンの簡易な高感度定量法として極めて有用であり, 市販塩酸試薬中の亜硝酸イオンの定量に適用して満足な結果を得た.

A simple, rapid and sensitive method for the adsorptive voltammetric determination of trace amounts of orthophosphate is described. In order to obtain a flat background current curve, the conditions for the preparation of a glassy carbon electrode and the voltammetric measurements are optimized. Orthophosphate is accumulated as heteropoly blue on the pretreated glassy carbon electrode in an aqueous acidic molybdate solution containing vanadate and acetone at −0.2 V vs. the saturated calomel electrode (SCE) for 150 s with stirring, and then the reduced complex is reoxidized during a positive-going scan at a rate of 50 mV s−1 to 0.2 V vs. SCE. Only one distinct peak is found at around 0.01 V vs. SCE. The calibration graph is linear over the 1 × 10−7to 1 × 10−6mol dm−3 concentration range of orthophosphate and passed through the origin, with a relative standard deviation (n = 6) of 4.3% for 5 × 10−7mol dm−3. The detection limit (3σ) was 1 × 10−8mol dm−3 (1.0 ng cm−3). Arsenate, which forms heteropoly acid wi...

The correlation between vegetation index and physical parameters of vegetation was analyzed in order to monitor vegetation in an arid area based on satellite data. Results indicate that the vegetation index is highly correlated with physical parameters of vegetation, in particular, dry biomass and leaf area index (LAI). However the correlation coefficient between vegetation index and vegetation coverage is slightly low. Results of vegetation monitoring based on satellite data which are analyzed by an algorithm we developed can be utilized to study desertification and the vegetation environment.

超臨界領域での水熱固化反応を焼却灰の安定な固化体への転化に利用するため, 黒鉛製パッキンの考案により, 500℃, 64MPa (630気圧) の条件で使用可能な水熱ホットプレス装置を開発した。この装置を用いた模擬焼却灰の固化実験において, 従来の水熱ホットプレス条件 (250℃, 64MPa) では新たな鉱物相の形成は認められなかったが, 超臨界条件 (500℃, 64MPa) で作製した固化体では3種の新たな鉱物相が形成された。

A simple and rapid procedure is presented for the reliable determination of antimony in steel based on differential pulse anodic stripping voltammetry without any removal of iron matrix. Optimum conditions included a supporting electrolyte of 0.1 mol dm-3 nitric acid-0.1 mol dm-3 sulfuric acid, a pre-electrolysis of -0.5 V vs. the saturated calomel electrode for 300 s at a rotating gold film electrode, and subsequent stripping of the deposit on the electrode surface by a positive going potential scan at a rate of 40 mV s-1. Antimony(V) was chemically reduced to antimony(III) by potassium iodide prior to voltammetric measurements. The interference of iron(III) was eliminated by simultaneously reducing it to iron(II) with the iodide. The generated iodine was reduced with L(+)-ascorbic acid. Arsenic(III), bismuth(III) and copper(II) interfered with the antimony determination severely. The proposed method has been successfully applied to the determination of antimony at the µg g-1 level in steels within 50 min without any troublesome preconcentration steps using harmful chemicals. The detection limit (3σ) with a deposition time of 300 s was 0.19 ng cm-3 (1.6×10-9 mol dm-3).

A simple procedure is described for the anodic stripping voltammetric determination of arsenic and antimony in iron and steel by adjusting the deposition potential in an acidic medium. Arsenic(V) and antimony(V) were reduced to the trivalent state with potassium iodide prior to the voltammetric measurements. Antimony(III) alone in the sample solution was first deposited on a rotating gold film electrode at −0.25 V vs. SCE for 180 s and was determined from the area of the stripping peak obtained by a positive going scan at 40 mV s−1 to 0.2 V vs. SCE. Next, both arsenic(III) and antimony(III) were deposited at −0.45 V vs. SCE for 180 s in another solution and the peak area was measured by anodic stripping. The arsenic concentration was calculated by difference. The interference of iron(III) was eliminated by reducing it to iron(II). The proposed method has been successfully applied to the determination of 50 to 450 μg g−1 each of arsenic and antimony in steels within 50 min without preliminary separation of...

A portable apparatus developed by one of the authors to measure the Bidirectional Reflectance Factor (BRF) over the spectral range 300–1100nm is described. Preliminary results of BRF for vegetation of different height and bare land indicate an effect of view direction on BRF. The analysis of the observed data also indicates that the larger the vegetation size the larger the dependence of reflectivity on viewing direction.

A simple and reproducible method is described for the determination of traces of tellurium(IV) based on differential pulse cathodic stripping voltammetry without the addition of any other metal ions to an acidic medium. Tellurium(IV) ions in a 0.18 mol dm -3 hydrochloric acid-0.20 mol dm -3 nitric acid solution (4 cm 3 ) were electrodeposited on a rotating silver disk electrode (2000 rpm) as silver telluride at -0.45 V vs. Ag/AgCl for 30 min. A cathodic stripping voltammogram was then recorded in an another solution (2 mol dm -3 sodium hydroxide) at a scan rate of 50 mV s -1 to -1.5 V vs. Ag/AgCl. Only a single well-defined peak could be seen at -1.16 V vs. Ag/AgCl. The calibration curve was linear up to at least 300 ng cm -3 of tellurium(IV) (2.4×10 -6 mol dm -3 ) and passed through the origin with an RSD of 6.8% for 50 ng cm -3 (n=5). The detection limit (3σ) was 0.62 ng cm -3 . The possible interferences were evaluated.

カソーディックストリッピングボルタンメトリーにおける前電解と溶出過程の電解液を換えることにより,ミリグラム鋼試料中のμgg-1レベルの硫黄を定量することができる簡便な高感度分析方法を開発した.酸分解した試料溶液中の硫酸イオンをヨウ化水素酸-ホスフィン酸混液で還元し,発生した硫化水素を0.2M水酸化ナトリウム溶液(4 ml)に吸収した後,-0.4 Vvs. SCEで30分間前電解し,約70%の硫化物を回転銀ディスク電極上に硫化銀として電着した.溶出は,2M水酸化ナトリウム溶液中,50mV s-1の速度で-1.5 Vvs. SCEまで電位を走査し,示差パルス法により電流-電位曲線を記録した.検量線は2.5～40ng ml-1の範囲で原点を通る直線となり,10ng ml-1でのRSD(n=5)は2.9%であった.支持電解質溶液変換法を採用した本法は,単一のピークが得られるため,複数個発生するピーク高さの和から硫黄を定量する既報の方法よりも感度,精確さが優れ,検出限界は0.25ng ml-1,分析所要時間は約2,5時間であった.

A new, simple, and reproducible method is described for the determination of selenium(IV) based on differential pulse cathodic stripping voltammetry. The optimized experimental conditions are as follows: selenium(IV) ions in an acidic medium (0.06 M HCl-0.07 M HNO(3)) are electrodeposited on a rotating silver disk electrode as silver selenide at -0.4 V vs SCE for 30 min; the deposit is then cathodically stripped in another solution (2 M NaOH) at a scan rate of 50 mV s(-1) to -1.2 V vs SCE. The cathodic stripping results in only a single well-defined peak at about -0.95 V vs SCE. The calibration (peak height vs selenium concentration) graph is linear up to at least 40 ng mL(-1) of selenium(IV) and passes through the origin, with a relative standard deviation of 2.7% for 20 ng mL(-1) (n = 5). The detection limit (3σ) is 0.20 ng mL(-1). The possible interferences have been evaluated. Dissolved oxygen does not affect the peak height of selenium. The electrode can be used repeatedly at least 20 times with excellent reproducibility without further polishing. The proposed method is an improvement over the existing cathodic stripping techniques.

The analysis of the data of sea surface temperature observed with a portable infrared radiometer from the fixed point on the seashore indicates a significant effect of observation(look) angle when it becomes larger than 70 degrees. An attempt is made to explain the effect by applying Fresnel's reflection law. A verification indicates a good agreement between the sea surface temperature observed with a portable thermal IR radiometer at large observation angles and that computed from Fresnel's reflection equation.

In an attempt to utilize satellite data to obtain land surface features of Taklimakan Desert in China, in situ measurements of spectral reflectance of the land surface is made the portable spectro radiometer in the spectral range of 400 ∼ 2500 nm. The analyses of the data show following features. (1) The difference in spectral reflectance of different soils is comparatively small. (2) There is a tendency that spectral reflectance of soils increases with increases of wavelength, for example, the average reflectance of the sands in the periphery areas of Taklimakan Desert is 21 and 38% in visible and near infrared spectra respectively. (3) It is found that reflectance of the soils decreases with increase of moisture content. The large decrease is recognized in 1450 and 1950 nm spectra, water absorption bands. This fact suggests that the monitoring of soil moisture is possible by measuring the radiance at these spectra, thus Landsat TM Bands 5 and 7 will be effective for monitoring soil moisture content.

The oligomycin B spiroketal portion, [2S,2(2R),3S,6R,8S,8(3R),9S,10R,11S]-2-[2-(t-butyldiphenylsilyloxy)propyl]-8-[3-(hydroxymethyl)pentyl]-3,9,11-trimethyl-1,7-dioxaspiro[5.5]undecane-5,10-diol (2), and polypropionate portion, ethyl (2E,4S,5R,6R,7S,8S,9R,10S,12R,13S,14R,16E)-5-(t-butyldimethylsilyloxy)7,9-(isopropylidenedioxy)-12,13-(4-methoxybenzylidenedioxy)-4,6,8,10,12,14-hexamethyl-11-oxo-18-phenylsulfonyloctadeca-2,16-dienoate (3), have been synthesized. The C19-C21 Wittig salt, [(2S,3R)-2-ethyl-3,4-(isopropylidenedioxy)butyl]triphenylphosphonium iodide (6), prepared from 2-butene-1,4-diol via Sharpless epoxidation, was coupled with the C22-C27 aldehyde, benzyl 2,4-dideoxy-3-O-(4-methoxybenzyl)-2,4-di-C-methyl-α,β-L-galacto-hexodialdopyranoside-(1,5) (7), prepared from (Z)-2-butene-1,4-diol via Sharpless epoxidation and the Brown’s crotylboration. The resulting coupling product was transformed to the C19-C27 lactone, [3S,4R,5R,6S,6(3R,4R)]-6-[3-ethyl-4,5-(isopropylidenedioxy)pentyl]-4-(4-methoxybenz...

The optimization of a stable austenitic F5 (18Cr-35Ni-Mo) steel was carried out by means of electron beam refining and the SAR treatment with a scavenger element Ti. Excellent irradiation resistance was confirmed by simulation tests of the irradiation induced degradation that is controlled by interactions between supersaturated solutes and crystal defects like dislocations.

The enantiospecific synthesis of the oligomycin B degradation product 2 , corresponding to the C19–C34 spiroketal portion, has been achieved by sequential coupling of the C19–C21, C22–C27, and C28–C34 subunits, establishing the absolute stereochemistry of oligomycin B.

A novel and efficient synthesis of 2,6-dideoxy-α-glycosides was developed by use of phenyl 2,6-anhydro-1,2-dithio-D-altropyranosides as glycosyl donors in a highly stereocontrolled glycosylation.

The oligomycin B spiroketal portion, [2S,2(2R),3S,6R,8S,8(3R),9S,10R,11S]-2-[2-(t-butyldiphenylsilyloxy)propyl]-8-[3-(hydroxymethyl)pentyl]-3,9,11-trimethyl-1,7-dioxaspiro[5.5]undecane-5,10-diol (2), and polypropionate portion, ethyl (2E,4S,5R,6R,7S,8S,9R,10S,12R,13S,14R,16E)-5-(t-butyldimethylsilyloxy)7,9-(isopropylidenedioxy)-12,13-(4-methoxybenzylidenedioxy)-4,6,8,10,12,14-hexamethyl-11-oxo-18-phenylsulfonyloctadeca-2,16-dienoate (3), have been synthesized. The C19-C21 Wittig salt, [(2S,3R)-2-ethyl-3,4-(isopropylidenedioxy)butyl]triphenylphosphonium iodide (6), prepared from 2-butene-1,4-diol via Sharpless epoxidation, was coupled with the C22-C27 aldehyde, benzyl 2,4-dideoxy-3-O-(4-methoxybenzyl)-2,4-di-C-methyl-α,β-L-galacto-hexodialdopyranoside-(1,5) (7), prepared from (Z)-2-butene-1,4-diol via Sharpless epoxidation and the Brown’s crotylboration. The resulting coupling product was transformed to the C19-C27 lactone, [3S,4R,5R,6S,6(3R,4R)]-6-[3-ethyl-4,5-(isopropylidenedioxy)pentyl]-4-(4-methoxybenz...

To investigate the role of the 2'-hydroxy group at the C-13 side chain of docetaxel in the antitumor activity, we prepared several 2',2'-difluoro derivatives of docetaxel and evaluated their cytotoxicity against mouse leukemia and human tumor cell lines and their microtubule disassembly-inhibitory activity. These analogues were prepared by esterification of protected 10-deacetylbaccatin III (21) with appropriate alpha, alpha-difluorinated carboxylic acids (Charts 1 and 2). Among these 2',2'-difluorodocetaxel derivatives, 2',2'-difluorodocetaxel (23b) was approximately 3-10 times as active as 2'-fluorodocetaxel (29a) in terms of cytotoxicity. In addition, the 3'-(2-furyl) (23h) and 3'-(2-pyrrolyl) (23p) analogues showed activity comparable or superior to that of docetaxel (2).