The "vicinal steps" on a substrate surface are useful to control in-plane orientations of organic thin-film crystals at a "nucleation" stage. In addition to a "nucleation" process, we also focused attention on a "growth" process, on which vicinal steps should also give their effects. Hence, we grew Pentacene (Pn) thin film crystals on vicinal hydrogen-terminated Si(111) (H-Si(111)) surfaces, and studied the effects of vicinal steps of H-Si(111) on the growth of the Pn thin film crystals by observing the morphology of the thin film with atomic force microscopy. We found that the first layer of the Pn thin film crystals exhibited a significantly anisotropic shape on a vicinal H-Si(111) surface: dendritic branches evolved in a lower terrace side (Si[112] direction) but compact shape appeared in an upper terrace side (Si[112] direction), although the first layer showed an isotropic shape on a flat H-Si(111) surface. Furthermore, the growth of the first layer was much faster in the lower-terrace-side direction than in the upper-terrace-side direction. Since such anisotropic growth was observed irrespective of the directions of an incident Pn molecular beam, we tentatively concluded that the cause of the anisotropic growth would be the anisotropy in the incorporation kinetics of Pn molecules at the edges of the thin film crystals on a vicinal surface.

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1.腐造性乳酸菌Lactbacillus casei B-158を純米やわくち酒に接種したところ, つわり香の主成分であるジケトンを著量生成した。
2. ソフトタイプ清酒の火落ち防止対策として, メタ重亜硫酸カリウムの添加がきわめて有効であり, 食品衛生法により定められている使用基準30mg/l内で十分その効果を認めた。
3.純米やわくち酒にメタ重亜硫酸カリウムを添加した場合すべて結合型亜硫酸で存在し, 火入れによりその含有量は減少しなかった。

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CoreyおよびWinterによって開発されたヒジナルジオール基の炭素-炭素二重結合への2工程による変換反応の適応性について, いくつかのタイプ別にジオールを有するステロイドについて検討した。ジオールを有するステロイドから誘導された環状チオノカーボネートをトリエチルフォスファイトと加熱環流することにより, 対応するオレフィン系ステロイドへ高収率で変換された。この2工程変換反応を鍵反応に用いて, ブラシノステロイド関連化合物である (22R, 23R, 24S) -and (22S, 23S, 24S) -2α, 3α, 22, 23-diepoxy-B-homo-7-oxa-5α-stigmastan-6-onesを既に報告されている方法よりもより効率的に合成した。

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2-Bromo-1-alkenes have been recognized as one of useful functional groups for preparation of vinyl lithiums and vinyl Grignard reagents, for coupling partners in a wide range of transition metal-mediated coupling reactions, substrates of radical reaction, and precursors of α-haloketones. Selective elimination reaction of 1,2-dibromides possessing O-aryl or O-acyl groups at the C3 position into 2-bromo-1-alkenes under mild basic conditions was developed. It can be explained that this regioselective elimination proceeds by inducing the acidity of hydrogen atom at the C2 position by the electron-withdrawing effect of the oxygen functional group at the adjacent position. Even in the case of vicinal dibromoalkane units at internal positions in carbon chain, a similar regioselective trans-elimination reaction took place, despite the syn- or anti-orientation of vicinal dibromides. As application of this regioselective elimination reaction, total synthesis of biologically active natural products, such as 12-oxygenated-tremetones, tuliparin B, and tanikolide, were accomplished. In addition, a synthetic study on seco-germacrane lactone by using the regioselective HBr elimination reaction and Pd-mediated coupling reaction as key steps was carried out. Alkynes are also one of the important functional groups as precursors of cis- and trans-1-iodo-1-alkenes, 2-iodo-1-alkenes, metalated alkenes and alkynes, and for substrates of organometal-conducted coupling reactions. HBr elimination reactions of 1,2-dibromides using LiHMDS, NaNH_2, etc., have been reported as synthetic methodologies of terminal alkynes. However, carbonyl functions such as lactones and ketones would react under the conventional methods. During our extensive investigation, the acidity enhancement of hydrogen at the C1 position by O-functional groups at the C3 position was also observed. This observation indicated a new prospective synthesis of alkynes from 1,2-dibromides under the DBU conditions. As demonstration of the versatile availability of the alkyne-syntheses condition, total syntheses of biological active lactone natural products muricatacin and (R,R)-sapinofuranone B were successfully achieved.

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連続不斉炭素中心にブロモ基ならびにクロロ基が隣接する構造を有するテルペン類の多くは，海洋資源から単離され，ユニークな生理活性を示すことが知られている．一方でその選択的な合成法に関しては，これまで十分に開拓されていなかった．今回Burnsらは，独自に開発した化学・位置およびエナンチオ選択的ジハロゲン化反応を応用し，1975年に紅藻類Portieria hornemanniiから単離されヒトがん細胞に対して前例のない活性プロファイルを示す2）海洋天然物（＋）-halomon（1）の不斉合成に成功したので，以下に紹介する．
なお，本稿は下記の文献に基づいて，その研究成果を紹介するものである.
1) Hu D. X. et al., J. Am. Chem. Soc., 137, 3795-3798 (2015).
2) Fuller R. W. et al., J. Med. Chem., 35, 3007-3011 (1992).
3) Bucher C. et al., J. Am. Chem. Soc., 137, 12784-12787 (2015).
4) (a) Schlama T. et al., Angew. Chem. Int. Ed., 37, 2085-2087 (1998) ; (b) Sotokawa T. et al., Angew. Chem. Int. Ed., 39, 3430-3432 (2000).

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The strategies for the development of fluorescent derivatization reagents for highly sensitive analysis of biomolecules, for example AE-OTf for carboxylic acids, (S) -2A1P-OTf for chiral carboxylic acids having chiral center at the remote position from carboxyl group and (S) -TBME carboxylic acid for “on-line HPLC-exciton CD analysis” of vicinal diols, diamines, and amino alcohols are discussed.

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米焼酎においても減圧蒸気による製品が主流になってきている。同じ原料を用いた焼酎でも蒸留法によりその香味は大きく異なり, 望ましい香味特性として要求される成分も再検討が必要である。このような視点から, 減圧蒸留の米焼酎の香気成分と官能評価との関係を見直し, さらに好ましい香りを多くし評価を悪くする成分を低減する目的で焼酎酵母の育種を行い, 実用にまで至った研究成果について解説していただいた。

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Marine microorganisms are potentially prolific sources of highly bioactive secondary metabolites that might represent useful leads in the development of new pharmaceutical agents. As part of our ongoing search for new antitumour metabolites produced by microorganisms from marine organisms, penochalasins A (1)-C (3) have been isolated from a Penicillium sp. originally separated from the marine alga Enteromorpha intestinalis. Furthermore, penostatins A (4)-D (7), F (8) and G (9) have been isolated from this fungal strain cultivated in a different medium from that used for production of penochalasins. The stereostructures and conformations of these metabolites have been elucidated by spectroscopic analyses and some chemical transformations. Penochalasins are a novel class of cytochalasans including a pyrrole ring and exist in different conformers arising from rotation of the C-3-C-10 and C-10-C-3' axes in CDCl_3 and pyndine-d_5. Penostatins A (4)-D (7) and G (9), and F (8) are three-cyclic terpenes including dihydropyran and including cyclooctadienone, respectively. Among these compounds, 1-6 and 8 exhibited significant cytotoxicity against cultured P388 cells.

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Based on the fact that some of the bioactive materials isolated from marine animals have been produced by bacteria, we have focused our attention on new antitumor materials from microorganisms inhabiting the marine environment. As part of our ongoing search for new antitumour metabolites produced by microorganisms from marine organisms, halichoblelide A (1)-C (3) have been isolated from a strain of Streptomyces hygroscopicus OUPS-N92 originally separated from the marine fish Halichoeres bleekeri. Compounds 1-3 were assigned the molecular formulae C_<54>H_<85>O_<19>, C_<51>H_<84>O_<15> and C_<50>H_<82>O_<15>, respectively, as deduced from [M+Na]^+ peaks in HRSIMS. The absolute stereostructures for these metabolites have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and CD spectra for the dibenzoates of the degradation products of these compounds. All these compounds exhibited potent cytotoxicity in the P388 lymphocytic leukemia test system in a cell culture.

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During the course of our search for biologically active metabolites in marine invertebrates, we have found that the organic extract of an Australian sponge of the genus Ianthella (order Verongida) showed potent inhibitory activity against Na, K-ATPase. From the EtOAc soluble portion six novel metabolites, named iantherans A and B (1 and 2) and ianthesines A-D (3-6), were isolated as active components. The structural determination of these compounds was accomplished by spectroscopic analyses and chemical derivatizations. The symmetrical molecule iantheran A(1) comprises a quite rare structure of a 1,4-disubstituted 2,3-bis(sulfooxy)-1,3-butadiene and two brominated benzofurans. Iantheran B (2) is the geometric isomer of 1 containing a (Z,E)-1,3-butadiene moiety. Ianthesines are all dibromotyrosine-derived metabolites with a spirocyclohexadienylisoxazoline moiety. Ianthesines A, B, and D (3, 4 and 6) are derived from two bromotyrosines, and ianthesine C (5) is a tetramer possessing eight bromine atoms and the molecular weight of 1606. The absolute stereochemistry of ianthesines were partially determined by degradation and CD spectroscopic method. The inhibitory activity of 1-6 and two derivatives of 1 against the dog kidney Na, K-ATPase was evaluated by a convenient HPLC-assisted assay method. The most active 1 inhibits the enzyme at IC_<50>=4μM.

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2-Bromo-1-alkenes have been recognized as one of useful functional groups for preparation of vinyl lithiums and vinyl Grignard reagents, for coupling partners in a wide range of transition metal-mediated coupling reactions, substrates of radical reactions, and precursors of a-haloke-tones. Selective elimination reaction of 1, 2-dibromoalkanes possessing aryloxy or acyloxy groups at the C 3 position into 2-bromo-1-alkenes under mild basic conditions was developed. Alkyne units are also one of the important functional groups for substrates of C-C coupling reactions. During our extensive investigation, the acidity enhancement of hydrogen at the C 1 position by oxygen-functional groups at the C 3 position was also observed. This observation indicated a new prospective synthesis of propargyl ethers from 1, 2-dibromoalkanes using DBU as a base. As application of these elimination reactions, total synthesis of biologically active natural products was accomplished.

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Oxidation is a most important transformation in organic synthesis. Many methods and reagents have been developed to date; however, these reactions typically involve the use of large quantities of heavy metals and complex organic compounds, which generate large amount of waste, and are not environmentally benign. Molecular oxygen has received much attention as an ultimate oxidant, since it is photosynthesized by plants, produces little waste, is inexpensive and of large atom efficiency than that of other oxidants. With this perspectives, we have found that methyl aromatics effectively oxidized to benzoic acids by photooxidation with molecular oxygen as terminal oxidant in the presence of 2-chloroanthraquinone. In the course of further our study, vicinal -diols were found to be oxidatively cleaved to corresponding carboxylic acids with molecular oxygen as terminal oxidant in the presence of 2-chloroanthraquinone under irradiation with a 400 W high-pressure mercury lamp.

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We present two new NMR techniques prepared by modification of HMBC, High Resolution HMBC (HR-HMBC) and BIRD-J- resolved HMBC. 1) High Resolution HMBC (HR-HMBC) In the conventional HMBC spectra, the cross peaks contain information on the long-range J_<CH> splittings and/or J_<HH> splittings. Due to the poor resolution in the F_2 or F_1 dimension, however, it is difficult to measure the long-range J_<CH> couplings directly from HMBC cross peaks. In order to solve this problem, we have incorporated the J-scaling method into HMBC and developed a new technique, HR-HMBC. The J-scaling pulse (--nt_1/2-180(H, C)-nt_1/2--) is introduced after the spin evolution period of HMBC. In this pulse sequence, the magnetizations of chemical shift, J_<HH> and J_<CH> coupling constants evolve with t_1, (n+1)t_1 and nt_1, respectively. As a result, the spin coupling constants are amplified by a factor of n for J_CH and n+1 for J_<HH> (n=20 to 30). This modification enables to determine easily long range J_<CH> couplings of complicated compounds and will be useful for conformational analysis of non-cyclic systems. Advantages of this method are simple operation, high sensitivity and general applicability. 2) BIRD-J-resolved HMBC For stereochemical studies of organic molecules by NMR, it is important to analyze proton-proton spin coupling constants. Natural products such as polyketide often contain the spin system which includes a secondary methyl group (-CH_A-CH_B(CH_3)-CH_C-). In such a spin system, proton H_B splits complicatedly. Thus, it becomes very difficult to obtain spin coupling constants from the multiplet signal of H_B. Analysis of spin coupling pattern of HB is sometimes essential for stereochemical studies. The new NMR techniques BIRD-J-resolved HMBC and BIRD-HR-HMBC are useful in order to overcome this problem. We have already reported J-resolved HMBC methods to observe long range J_<CH> couplings. By incorporation of the scaling pulse into HMBC, proton-proton spin splittings in the F_1 dimension are magnified by a factor of n (n=20 to 30) making measurement of J_<CH> very easy. In these pulse sequences, 180 pulse is put into BIRD pulse. The BIRD pulse modulates only protons directly connected to ^<12>C and not protons connected to ^<13>C. In other words, protons connected directly to ^<13>C are decoupled. For example, in a spin system (-CH_A-CH_B(^<13>CH_3)-CH_C-), proton H_B with its adjacent methyl protons being decoupled are coupled only to H_A and H_C in J-resolved HMBC and HR-HMBC spectra. Thus this technique enables easier analysis of the multiplet H_B with complicated splitting pattern. An application of this method to a model compound portmicin is explained.

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生物活性天然物の絶対配置を含めた全構造を決定することは、その分子サイエンスを展開する上で必須の極めて重要なステップである。現在では、NMR を中心とした構造解析により複雑な構造多様性をもつ天然物の全構造決定が可能になってきてはいるが、分光学的手法においても技術限界があり、その解決法が強く切望されている。特に立体構造が完全に決まらない場合が多々見受けられ、当研究室では有機合成の立場からそのような問題に取り組んで来た¹。本討論会においては、NMR を中心とした構造解析により部分的な立体構造しか解明されていない細胞毒性海洋産含臭素オキサスクアレノイド (+)-ユーボールの不斉全合成を達成することにより提出構造式の改訂を行うとともに、類縁体 (+)-22-ヒドロキシ-15(28)-デヒドロベヌスタトリオールの不斉全合成も達成し、それらの全立体構造を決定したので報告する。

ユーボールと22-ヒドロキシ-15(28)-デヒドロベヌスタトリオール（推定構造式をそれぞれ1a and 2a で表す）は2011 年大西洋のマカロネシアにあるカナリア諸島周辺の紅藻Laurencia viridis から、Fernandez らにより微量成分として単離、構造決定されたオキサスクアレノイドである（Scheme 1）²。これらの化合物はJurkat 腫瘍細胞に対し、それぞれIC₅₀ = 3.5 and 2.0 μM で成長阻害活性を示す。平面構造は二次元NMR スペクトルにより決定された。A,B,C 環部分の相対配置は同じく1984年にMartinらによって紅藻Laurencia pinnatifidaから単離された絶対配置既知の類縁体デヒドロチルシフェロールのNMR スペクトルデータ³との比較により決定され、D 環の構造および相対配置はNMR スペクトル解析及び生合成仮説に基づき推定されている。しかしながらA,B,C 環とD 環はアルキル鎖で隔てられており、両フラグメント間での相対的な配置及び分子の絶対配置は未決定である。我々はこれら微量成分である両天然物の絶対配置を含めた全立体構造の解明のためには、やはり有機合成によるアプローチが有効であると考え、それらの合成研究に着手した。またこれら微量成分の構造活性相関研究や作用機序解明等のためには、誘導体合成が可能な柔軟性のある化学合成法の確立が必要不可欠である。

合成計画をScheme 1 に示す。両化合物のA,B,C 環部は共通であり違うのはD 環部だけなので、C15–C16 部分で二つのフラグメント3と4 (or 5) に分け、両者を鈴木−宮浦クロスカップリングにより収束的に連結する計画である。連結後、A 環をブロモエーテル化により構築する。THP 環が縮環したB,C 環3 は、エポキシド7 とスルフィド8 を連結したアルコール6 を適当なエポキシアルコールへと誘導した後、順次6-exo オキサ環化により構築する。B,C 環部の合成法はいくつか報告されているが、C 環部は図に示すようなツイストボート型の構造をとっている事が知られており、C14位のエピマー化が起こらないマイルドかつ効率的な構築法を開発する必要がある。7 は既知の光学活性エポキシアルコール9⁴ から導く。1a のD 環部4 は、既知の光学活性ジオール10 から化学量論的Sharpless 不斉エポキシ化を経て調製する。2a のD 環部の場合はC22 位のヘミケタールを分

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