著者

樋口 隆一 時光 義徳 古森 徹哉

出版者

天然有機化合物討論会実行委員会

雑誌

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巻号頁・発行日

vol.28, pp.224-231, 1986

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Mechanisum of the diazomethane degradation for the sugar-aglycone linkage of the gypsogenin 3-O-glycoside(1) was studied and the useful degradative reaction was applied to the structure determination of quillayasaponin. Since three kinds of functional groups of 1, the 4α-CHO group in the aglycone, COOH and 4-OH group in the glucuronic acid were presumed to contribute to the degradative reaction, the necessarity of the each functional group was examined using a model compound 7, and only the 4α-CHO group was showed to be essential. By taking the above evidence and the usual reaction products of aldehyde with diazomethane into account, the reaction must be proceeded through such a oxide intermediate as shown in the scheme 6. QS-III(25), a major acylated genuine bisdesmoside of the so-called quillayasaponin, afforded a 28-O-glycosidal triterpenoid(29) still possessing acyl moiety by this diazometane degradation. On the basis of chemical and spectral evidence, especially, comparison of the ^<13>C NMR spectra of 29 and its desacyl compound(30)(Table 1), the site of linkage of acyl moiety of 29 was determined. The structure of 25, therefore, was complex acylated oligosaccharide as shown in scheme 8.

著者

平田 義正 江口 昇次 下村 脩

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天然有機化合物討論会

雑誌

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巻号頁・発行日

no.3, pp.83-93, 1959-10-17

著者

鈴木 智大 川口 卓巳 天野 裕子 小林 夕香 森田 達也 長井 薫 新井 信隆 河岸 洋和

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天然有機化合物討論会

雑誌

天然有機化合物討論会講演要旨集

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no.48, pp.325-330, 2006-09-15

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In autumn, 2004, 55 people got poisoned by eating an edible wild mushroom, Pleurocybella porrigens (Sugihiratake in Japanese) and 17 people among them died of acute encephalopathy. We found that mice died by injection of the wter-soluble extracts of the mushroom. We tried the isolation of the toxic principle(s) from the extracts. As a result, a lectin (PPL) and a glycoprotein were purified from the mushroom. PPL is a tetramer of identical subunits without S-S linkage. The lectin specifically bound N-acetylgalactosamine among monosacchrides tested. This lectin showed lethal toxicity against rats. In addition, a glycoprotein was isolated as a lethal toxin against mice and rats. The relation between these substances and acute encephalopathy is now being elucidated.

著者

丸山 雅雄 寺原 昭 中平 靖弘 Woods M. C. 板垣 又丕 高木 良子 中西 香爾

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天然有機化合物討論会

雑誌

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巻号頁・発行日

no.10, pp.238-245, 1966-09-15

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From the root bark of Ginkgo biloba L. ("icho" in Japanese), a unique fossil tree which has remained unchanged for 1-2 million years, four bitter principles designated ginkgolides A, B, C and M (for "minor") (abbreviated to GA, GB, GC and GM) have been isolated. Early work was greatly hindered by purification problems and polymorphism, but the molecular formulae were finally settled by high resolution MS of GA dimethyl ether (Fig. 1). As shown in Fig. 2, a tert-Bu group is present; these are the first plant products to contain such a group. Establishing the number of lactone groups presented difficulty, but was achieved by titration according to Method B (Fig. 3). The partial structure comprising rings A/B was elucidated from the data summarized in Figs. 5 and 6. NMR analysis of the isolated 4 proton system E-H (Fig. 7) was simplified in GC because of an additional 2°-OH group. The bislactone system containing H_J was clarified (Figs. 8-10) by an NMR analysis of GA-triether utilizing extensively the techniques of solvent shifts and decoupling, and comparison with the triether-d_6 spectrum which resembles the GA spectrum (Fig. 13). An attempt to determine the number of lactone rings was made by measuring the M^+ and isotope peaks of GA dimethyl ether (Fig. 11), the lactone rings of which had been cleaved and recyclized in the presence of H_2O^<18> as depicted in Fig.13-Method B. However, the MS indicated that only two lactones had incorporated O^<18>; presumably, one of the lactones had been cleaved by O-alkyl fission and recyclized by expulsion of O^<18>H. Alkali fusion of GA gave two important bisnor products, but these are not discussed in the Abstract because of limitations of space. Part structures shown in Fig. 12 are proposed for the ginkgolides.

著者

松浦 正憲 加藤 優 犀川 陽子 乾 公正 橋本 貴美子 中田 雅也

出版者

天然有機化合物討論会

雑誌

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no.50, pp.415-420, 2008-09-01

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Accidental ingestion of a toadstool, Russula subnigricans causes lethal poisoning to human. In the 1950's, the first poisoning caused by this mushroom was reported. Since then there have been no reports about lethal poisoning for 50 years, which was enough to raise doubts about its existence. However, in these three years, 2005 to 2007, the poisoning accidents were continuously happened and four people died. Although chemical studies on this fungus were reported using mushrooms distributed in Miyagi prefecture, the isolated compounds, russuphelins, russupherol, and hydroxybaikiain, have no toxicity on mouse. Accordingly, we studied the isolation of the toxic constituent of R. subnigricans. One of the reasons that such a strong toxin has not been revealed until now is the incomplete classification of this mushroom, that is, there are many resemble species distributed in Japan. We collected three species in Kyoto, Miyagi, and Saitama prefectures. The aforementioned compounds were found only in the Miyagi species. All three species show toxicity on mouse by intraperitoneal injection of the water extract; however, only the Kyoto species exhibits toxicity by oral injection. Accordingly, we estimated that the Kyoto species is the genuine R. subnigricans. During the separation steps, we found that the toxicity was remarkably decreased after concentration to dryness; therefore, all manipulations were carefully performed. The water extract was successively separated through ODS column chromatography, ion exchange chromatography, and gel filtration to give an aqueous solution of the toxic compound. The toxic compound was revealed to be unstable under concentration to dryness (polymerization occurs) and volatile, which was turned out to be the cause of decrease in toxicity after evaporation. The unstable toxin was converted to a stable derivative using diphenyldiazomethane. Taking ^1H, ^<13>C NMR and MS spectral analyses of the toxic compound and its derivative into consideration, the structure of the toxic compound was determined to be cycloprop-2-ene carboxylic acid. This compound was found only in the Kyoto species.

著者

福井 祐子 岩下 孝 浅見 純生 野中 裕司 前田 満 橋本 文雄 木曽 良信

出版者

天然有機化合物討論会

雑誌

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no.50, pp.475-480, 2008-09-01

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Oolong tea is a semi-fermented tea, which has been manufactured from leaves of Camellia sinensis (L) O. Kuntze, same as non-fermented Japanese or Chinese green teas. Major components of fresh tea leaves are caffeine and catechins such as epigallocatechin-3-O-gallete (EGCG). During the fermentation process, polyphenol oxidase (PPO) in tea leaves oxidizes the catechins into theasinensin and oolongtheanin. In addition, oolonghomobisflavans are known as condensation products of catechins by heat treatment. The aim of this study is to quantify these minor polymerized polyphenols by LC-MS/MS, and address their biological activities. Quantification of polyphenols by LC-MS/MS Theasinensin (TSN), oolongtheanin gallate (OTNG), and oolonghomobisflavan (OHBF) were synthesized from EGCG. Two new trimers and tetramers of oolonghomobisflavan were synthesized along the previous synthesis method of OHBF, and then their structures were determined by MS and NMR spectroscopy. Quantification of these compounds was performed by LC-MS/MS in the mode of multiple reaction monitoring (MRM). Compounds other than TSN-A were of small quantities in oolong tea leaves. Quantification of polymerized polyphenols was not performed with HPLC UV monitoring, but by LC-MS/MS method. Nine kinds of oolong teas in different fermentation levels were extracted and analyzed. The very small amount of trimers and tetramers of OHBF were included in "Black oolong tea", therefore, it was necessary to make concentrated solutions of these by column separation, and quantified the real amount by analyzing them. Biological activities of polymerized polyphenols Pancreatic lipase inhibitory activity of oolong tea polymerized polyphenols (OTPP) and some catechin dimmers have been already reported. In this study, new trimers and tetramers also exhibited strong inhibitory activity. Besides OTPP, the polymerized polyphenols, TSN, OTNG, and OHBF also have α-glucosidase inhibitory activity. These results suggest that oolong tea prevents the elevations of triglyceride in blood from meal fat, as well as inhibit the absorption of sugars derived from carbohydrates.

著者

竹内 純 甲斐 建次 片岡 太一 横山 峰幸 渡辺 修治

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天然有機化合物討論会

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no.50, pp.439-444, 2008-09-01

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In the course of screening for endogenous flowering inducer, α-ketol of octadecadienoic acid (KODA, Figure1) was isolated from Lenma paucicostata. KODA showed the activity after reacting with norepinephrine (NE) under the basic conditions. Further investigations have revealed that FN1 is a major active compound, which is expected to be formed by cycloaddition between 12-olefin of KODA and α, β-unsaturated carbonyl of noradrenochrome, an oxygenated form of NE. However, the mechanism of flower-induction of FN has not been examined. In present study, we carried out the structure-activity relationship study of the fatty acid moiety of FN for flowering in L. paucicostata by using series of KODA analogs shown in Figure 2. Firstly, we synthesized nine fatty acid analogs, where single or combinative alterations have been made to the structural components of KODA and tested for their ability to induce flowering. With the exception of compounds 8, 10, 12, all these analogs proved to have a flowering activity after reacting with NE. Compound 4, in which 15-olefinic bond is saturated, displayed high activity of same magnitude as KODA. This suggested that olefinic bond at 15-position in KODA in not important for activity. Compounds 7 and 9 displayed a significant activity but less in magnitude as the parent KODA. This implied that 9-hydroxy group may not be involved in primary recognition of the target whereas the presence is favorable to show high activity. Compounds 5 and 6, in which their alkyl chains are shortened, displayed flowering activity at a concentration of more than 1μM. In addition to this, the biological result obtained with methyl ester 11 indicated that recognition of the aliphatic chain and terminal carboxy group in FNs is relatively obscure. On the other hand, compounds 8, 10, and, 12, changing of β, γ-unsaturated carbonyl moiety led to complete loss of activity in L. paucicostata. This result showed that cycloaddition of fatty acid with NE is inevitable process to induce flowering in L. paucicostata. Furthermore, to obtain clearly insight in the structural requirements of FN1 for flower inducing activity, we prepared FN derivatives from corresponding fatty acid analogs and evaluated their activity.

著者

滝川 浩郷 森 謙治 木戸 勝 Albizati K. F. Faulkner D. J.

出版者

天然有機化合物討論会実行委員会

雑誌

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巻号頁・発行日

vol.34, pp.707-714, 1992

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In 1985, limatulone (1a and 1b) was isolated from the intertidal limpet Collisella limatula, and found to inhibit fish and crab predation. It is the most potent fish feeding inhibitor and is about an order of magnitude more effective than polygodial. Although the natural limatulone was optically inactive, it was not clear whether it was a meso-compound (1a) or a racemate (1b). We therefore decided to confirm the structure by a total synthesis. The known 3, which was obtained from the starting material (2) in 4 steps, was alkylated with BrCH_2CO_2Et to give 4a. The corresponding acid 4b was employed for the lactone-ring formation to give a stereoisomeric mixture of lactones 5a and 5b. After separation, lactone 5a was converted to the coupling-partners 10 and 11 via 6, respectively. The carbanion derived from 11 was alkylated with 10 to give a complex mixture, which was desulfonylated with Na-Hg to give a mixture of 12a and 12b. This was converted to a separable mixture of 13a and 13b. Fortunately, the structure of the less polar isomer could be solved by an X-ray analysis. An aldehyde 15a, which was prepared from 13a in 3steps, was treated with ClCH_2Li to give bis-epoxide 16a. Epoxide-opening of 16a by a Grignard reagent gave 17a. Swern oxidation of 17a to 18a was followed by removal of the EE protective groups to give meso-limatulone (1a), (overall yield: 0.62% from 2 in 24 steps). Similarly, (±)-13b was converted to (±)-limatulone (1b), (overall yield: 0.39% from 2 in 24 steps). The ^1H-NMR spectrum of the reported limatulone was identical to that of (±)-limatulone (1b). To our surprise, however, another fraction from the HPLC of Collisella limatula showed the ^1H-NMR spectrum superimposable on that of meso-limatulone (1a). Accordingly, Collisella limatula produces both meso-1a and (±)-1b.

著者

北村 雅人 塚本 眞幸 別所 祐紀

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天然有機化合物討論会

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no.44, pp.533-538, 2002-09-01

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Asymmetric hydrogenation of -(acylamino)acrylic acid derivatives was first established by Kagan in 1971. A cationic (R,R)-DIOP-Rh complex smoothly hydrogenates an enamide substrate to give (S)- and (R)-phenylalanine derivatives in 7:93 ratio. This finding paved the way to asymmetric hydrogenation world as well as the synthesis of optically active natural and unnatural amino acids. A perfect enantioselection in the Kagan reaction was achieved by use of BINAP ligand (BINAP=2,2'-bis(diphenylphosphino)-1,1'-binaphthyl) in 1980 although the Rh complex suffered from the high substrate specificity. A breakthrough has been made by the discovery of BINAP-Ru complexes, which serve as excellent catalyst precursors for highly enantioselective hydrogenation of a variety of functionalized prochiral olefins and ketones including enamides, ,-and ,-unsaturated carboxylic acids, allylic and homoallylic alcohols. keto esters, hydroxy ketones, and amino ketones. Interestingly, the sense of asymmetric induction in the (S)-BINAP-Ru(II)-catalyzed Kagan reaction is opposite to that observed with (S)-BINAP-Rh(I) catalysts. In this paper, we would like to focus on the mechanism of the BINAP-Rh- and -Ru-catalyzed Kagan reaction that is the origin of highly enantioselective hydrogenation. Combination of isotope labeling experiments and kinetics has revealed that the reaction proceeds via a monohydride-unsaturate mechanism involving the initial RuH formation followed by a reaction with an olefinic substrate. The major S and minor R enantiomers are produced via the same mechanism. The detail rate law analysis made it possible to determine the energy diagram of the catalytic species, which has also been experimentally substantiated by the ^<12>C/^<13>C and ^1H/^2H isotope effect measurements. The Ru monohydride species B is first generated from the diacetate A and H_2, and then forms a short-lived enamide complex C which delivers the hydride to the C(3) position. The addition of the RuH species to the olefinic bond is endergonic and reversible. The overall rate is limited by the Ru-C hydrogenolysis step of the resulting Ru-alkyl species D. The enantioselection is made during this irreversible step but actually is controlled by the relative free energies of the diastereomeric RuH/olefin complexes. Structural information was obtained by NMR studies as well as X-ray crystallographic analysis. Crystalline mono-methanol coordinated diacetate complex and the derivative of the Ru monohydride species were isolated and characterized by X-ray study. The molecular structures are consistent with those in solution estimated from NMR experiments. The reaction monitoring by NMR using ^<13>C-labeled substrates revealed that the observed Ru-enamide complex is nonproductive and that the mode of enamide coordination corresponds with that in the reactive RhH_2 intermediate in the related Rh-catalyzed hydrogenation which occurs via a unsaturate-dihydride mechanism. All of the observation strongly support the enantioface selection based on the stereo-complementary models of the enamide/metal chelate complexes.

著者

今井 直子 オニヤンゴ エヴァンス 鶴本 穣治 高橋 圭介 石原 淳 畑山 範

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天然有機化合物討論会

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no.48, pp.181-186, 2006-09-15

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Oxazolomycin and neooxazolomycin are structurally closely related antibiotics isolated from Streptomyces sp. by Uemura et al. The former is the parent member of a class of polyene bicyclic antibiotics, other members being oxazolomycin B and C, 16-methyloxazolomycin, and curromycin A and B. The oxazolomycins were found to exhibit wide ranging and potent antibiotic activity, including inhibitory activity against Gram-positive bacteria, antiviral activity against vaccina, herpes simplex type I and influenza A, as well as in vivo antitumor activity. The intriguing molecular architectures and the biological activities make these compounds attractive targets for synthesis. However, the total synthesis is limited to Kende's synthesis of neooxazolomycin. We report here a novel approach to neooxazolomycin, which can be also applicable to the synthesis of oxazolomycin. Our synthesis of right hand core 22 started with methyl (S)-hydroxyisobutyrate and proceeded through three major transformations involving regio- and stereoselective iodination via intramolecular Pt-catalyzed hydrosilylation, Pd-catalyzed enolate alkenylation, and stereoselective dihydroxylation accompanied by concomitant lactonization. Nozaki-Hiyama-Kishi coupling of aldehyde 23 obtained from 22 with N-Fmoc-iododienamine 24 gave 7S-isomer 25 and 7R-isomer 26 as a 1: 1 epimeric mixture. It was gratifyingly found that Dess-Martin oxidation of this epimeric mixture followed by L-Selectride reduction of the resulting ketone produced the desired 7R-isomer 26 in excellent stereoselectivity (94% de). Removal of the silyl protecting group allowed us to obtain the Kende's intermediate 27, the synthesis of which constitutes a formal synthesis of neooxazolomycin.

著者

河岸 洋和 畠山 美奈 何 普明 杉山 公男

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天然有機化合物討論会

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no.42, pp.517-522, 2000-10-01

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In the course of screening for liver injury preventing activity of 22 fruits, we found strong activity of avocado. We describe the isolation, structure determination, and biological activity of the liver injury preventing substances from the fruit Lyophilized materials were extracted with hexane. The hexane extract was chromatographed on a silica gel column followed by HPLC using an ODS column, giving five compounds 1-5. FAB-MS (positive) of 1 showed the [M+H]^+ ion at m/z 351. Its ^<13>C-NMR and DEPT experiment exhibited the presence of a carbonyl group (δ189.2), 4 double bonds (δ126.3, 127.8, 128.3, 129.2, 129.8, 130.3, 144.8, 148.7), 11 methylene groups, and a methyl one (δ14.09). Finally, the structure of the compound was determined by the interpretation of HMBC spectrum and its EI-MS fragmentation. Compounds 2 and 3 have been already isolated as an antifungal substance and/or radical scavengers. Elucidation of the structures of compounds 4 and 5 is now in progress. In vivo assay was done as follows. After direct administration of each compound (100mg/kg weight) into rats' stomachs by using catheters, liver injury was induced by treatment of the rats with D-GalN. All the compounds suppressed the increase of ALT and AST activity in the serum of the rats.

著者

大船 泰史

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天然有機化合物討論会

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no.24, pp.560-567, 1981-09-10

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I. (-)-Domoic acid (2) isolated from Rhodophyceae (Chondria armata Okamura), possessing strong neuroexciting activity, has been synthesized in optically pure form. The reported structure was (2S,3R,4S) 1 with undefined stereochemistry at C-5' carbon atom. Including determination of C-5' configuration, we planned to synthesize 1 as a target molecule. Comparison of both synthetic epimers 21a and 21b with natural domoic acid derivative showed uncorrectness of the structure 1. So, X-ray crystallographic analysis was examined by Takemoto et al. As a result, structure 1 was revised to 2 with C-2', C-3' Z double bond and C-5' R configuration. The synthesis to 1 and then, 2 are in the following. 1) C-3 and C-4 side chain of the pyrollidine ring were introduced by means of Diels-Alder reaction (6 and 4-methyl-2-trimethylsilyloxy-trans-1,3-butadiene). 2) Chemoselective reduction of C-5 amide function in the presence of N-t-Boc protecting group was achieved using BH_3-DMS (9→10) 3) C-4 side chain (13→20a,20b) was constructed in four steps via hydroxyselenenylation and selenoxide elimination, followed by Wittig reaction with 18a (C-5'R) and 18b (C-5'S). Wittig reaction of 18a and 16b afforded 22, which was converted in three steps to (-)-domoic acid (2). II. 2'-Deoxymugineic acid (25) isolated from wheat root (Triticum aestivum L.) and avenic acid A (26) isolated from oat root (Avena sativa L.) were synthesized in the stereospecific manner employing N-alkylation procedure of three optically active unit.

著者

鈴木 輝明 武田 聡 鈴木 稔 黒沢 悦朗

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天然有機化合物討論会

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no.29, pp.576-583, 1987-07-25

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In our continuing work on the neutral extract of Laurencia obtusa (magiresozo in Japanese), which exhibited the remarkably cytotoxic properties, we previously reported the isolation and structure determination of strongly active squalene-derived polyethers. Further investigation of this extract has led to the isolation of five cytotoxic diterpenes (1)-(5), which are structurally related to parguerol or isoparguerol, along with inactive sesquiterpenes (6)-(9). The structures of these compounds were characterized by chemical and spectral methods.

著者

小口 剛正 渡邉 一弘 阿部 秀樹 加藤 正

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天然有機化合物討論会

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no.49, pp.521-526, 2007-08-24

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(-)-Nalanthalide (1), isolated from the culture of Nalanthamala sp., was found to be a novel blocker of the voltage-gated potassium channel Kv 1.3 by Merck research group. In human T cell, to block Kv1.3 channels cause to prevent membrane depolarization, which attenuates intarcellular Ca^<2+> levels for T cell activation and proliferation. Therefore, (-)-1 is expected to be a promising new lead for the immunosuppressant. A closely related diterpenoid α-pyrone (+)-sesquicillin (2), wherein the γ-pyrone ring of (-)-1 is replaced with an α-pyrone ring, was previously isolated from Acremonium sp. It was reported that (+)-2 shows a variety of biological properties such as glucocorticoid antagonist. anti-inflammatory, anticancer, and G1 phase arrest activities. We envisioned that (+)-(2) would be elaborated through conversion from the γ-pyrone ring of (-)-1 to the corresponding a-pyrone ring. And (-)-(1) would be available through a coupling of 4 with 3. The intermediate 5 would be available through the strategic [2,3]-Wittig rearrangement of 6. The synthesis began with the preparation of intermediate 6, the substrate for the key [2,3]-Wing rearrangement, starting from 8. After conversion of 8 to 6, we carried out the [2,3]-Wittig rearrangement under several reaction conditions. Finally, we found that the designed [2,3]-Wittig rearrangement of 6 proceeded smoothly and cleanly by treatment with n-butyllithium in n-hexane at-50℃→room temperature. In this reaction, the use of n-hexane as the solvent was crucial. After conversion of 5 into 4, the coupling of 4 with 3-Iithio-γ-pyrone was achieved an initial bromine/lithium exchange on 3. The coupling product was converted to the key intermediate 19. Acetylation of 19 furnished (-)-(1). Next, we attempted direct conversion of (-)-(1) to (+)-(2) under several basic conditions; however, undesired deacetylation of the C3 acetyl group in (-)-1 occurred. Consequently, conversion of the γ-pyrone ring in 19 to the α-pyrone ring under basic conditions was conducted; the desired diacetate 20 was obtained upon acetylation of the product. Finally, selective deacetylation of the α-pyrone moiety in 20 under mild basic conditions furnished (+)-(2).

著者

廣田 洋 棚橋 善昭 高橋 武美

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天然有機化合物討論会

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no.19, pp.54-61, 1975-10-01

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Structure elucidation of LB, one of the volatile components of "San-shion" (Ligularia species), was accomplished in the following way. LB, C_<15>H_<26>O, was assumed to be a saturated guaiane-type sesquiterpene ether from its spectra and the dehydrogenation reaction. INDOR experiments on LB and 1-epiguaioxide(13) showed that LB is one of the eight stereoisomers of guaioxide(10). As six compounds of them are already known, the structure of LB must be represented by either 14 or 16. The reaction of LB with NBS in CCl_4 gave 4-bromo-LB(22) in 8〜18% yield. The compound(22) was dehydrobrominated into 23, which reacted with diborane to give 27. The oxidation of 27 with Jones' reagent gave the ketone(29), which then isomerized to 26. The structure of 22, 23, 26, 27, and 29 were confirmed by their spectral data, obtained by double resonance and lanthanide-induced shift techniques in PMR. The absolute structure of 29 was determined by the ORD and CD experiments. The hydrogenation of 23 gave 4-epi-LB. The compound(14) obtained by tosylation of 27 followed by reduction with LiAlH_4, was identical with 4-epi-LB. Therefore, the structure of LB was determined to be 16, including the absolute configuration.

著者

紺野 勝弘 白浜 晴久 松本 毅

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天然有機化合物討論会

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no.25, pp.421-428, 1982-09-10

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Clitocybe acromelalga is a poisonous mushroom distributed in Japan only. It exhibits unique toxicity. If one takes it accidentaly, one will have intolerable pain in fingers and toes after some days and the pain continues for about a month. We were interested in these remarkable physiological activities. It was difficult to reproduce the above described symptoms in experimental animals, however. So we fractionated various constituents of the mushroom testing the lethal effect on mice. Clitidine was a weakly toxic, a new nucleoside. Clithioneine, an unusual betaine, was nontoxic. From the most toxic fraction, acromelic acid A (ca. 110μg) and acromelic acid B (ca. 40μg) were isolated. We suggest formula 1 and 2 for A and B respectively on the basis of ^1H NMR and UV data.

著者

石井 永 石川 勉 小林 純一 関 宏子

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天然有機化合物討論会

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巻号頁・発行日

no.34, pp.518-525, 1992-09-10

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Toddacoumalone (4) and toddacoumaquinone (5), isolated from Toddalia asiatica (L.) Lam. (T. aculeata Pers.) (Rutaceae), were established to be novel unique mixed dimers based on a coumarin by spectroscopic means mainly 2D-NMR. Toddacoumalone (4), C_<31>H_<31>NO_6, was isolated as colorless prisms, mp 202-204℃ (AcOEt), in a racemic form. Its IR, UV, and NMR (Table 1) spectra including the COLOC experiment based on three bond correlations (Table 2) indicated the presence of a 8-substituted 5, 7-dimethoxycoumarin like 6 and an N-methyl-2-quinolone like 7 in 4. A monoterpene bridge of CH=CHC(Me)CH_2CHCH=CMe_2 with cis arrangement between the two vinyl groups was interposed between the coumarin and the quinolone units. Though lack of coupling between the conjugated olefinic protons gave us no clue to the geometry, an E geometry for the double bond could be deduced by appearance of conjugated (E)-olefinic protons in toddalenol (12) as a 2H singlet and coexistence of toddasin (13) in the same plant. Connection of the C_<10> unit to the coumarin and the quinolone systems resulted in drawing the structure of 4 for toddacoumalone. Toddacoumaquinone (5), C_<23>H_<18>O_7, was isolated as orange prisms, mp 278-281℃ (AcOEt). The same 8-substituted 5, 7-dimethoxycoumarin moiety was also found to be in 5. In this case presence of an 8-substituted 2-methoxy-6-methyl-p-naphthoquinone system was reasonably deduced by spectral data. Thus, toddacoumaquinone should be a biaryl compound consisting of a coumarin and a naphthoquinone, the structure of which could be depicted as 5. Both the dimers would be synthesized in a plant body through Diels-Alder type cycloaddition reaction. The synthetic works based on this biogenetic consideration are now in progress.

著者

入江 一浩 増田 裕一 村上 一馬 上村 諭子 大東 肇 原 英之 大橋 竜太郎 中西 梓 竹腰 清乃理

出版者

天然有機化合物討論会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

no.49, pp.61-66, 2007-08-24

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Aggregation of the 42-mer amyloid β (Aβ42) plays a central role in the pathogenesis of Alzheimer's disease. Our recent research on the systematic replacement of Aβ42 with proline suggested that the formation of a turn structure at Glu-22 and Asp-23 could be essential to the potent aggregative ability and neurotoxicity of Aβ42. We verified the existence of this turn structure in the minor conformer of wild-type Aβ42 and E22K-Aβ42 (Italian mutation), by solid-state NMR using dipolar assisted rotational resonance (DARR). In E22K-Aβ42, the ionic interaction between Lys-22 and Asp-23 might promote the turn formation at this site. In order to identify the toxic conformation of Aβ42, we synthesized Aβ42-lactam(22K-23E) as a conformationally restricted analogue of the minor conformer, whose side chains of Lys-22 and Glu-23 are linked with an amide bond. Aβ42-lactam(22K-23E) showed much stronger aggregative ability and neurotoxicity than E22K-Aβ42. This implies that the minor conformer with a turn at Glu-22 and Asp-23 of Aβ42 should be considered as a toxic form. Neurotoxicity of Aβ42 is closely related to the radicalization at both Tyr-10 and Met-35. Our previous study reminds us that the S-oxidized radical cation at position 35, the ultimate toxic radical species, would be produced effectively through oxidation by the phenoxy radical at position 10 in the toxic conformer. Electron spin resonance (ESR) spectrometry using spin-labeling with MTSSL revealed that these residues are close to each other in Aβ42. This finding clearly accounts for the reason why the toxic conformer is more pathogenic than the physiological one.

著者

西沢 麦夫 山田 英俊 林 雄二

出版者

天然有機化合物討論会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

no.28, pp.370-376, 1986-09-09

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A sweet principle of Phlomis betonicoides, baiyunoside (1a) reported by Tanaka, is a glycoside of 3-substituted furanoditerpene with labdane skeleton. During the series of our investigation dealing with a biomimetic olefin cyclization using mercury(III) triflate/N,N-dimethylaniline complex (2), we have examined the cyclization of some acyclic furano terpenoid, and observed that the cyclization of ambliofuran (3a) is mainly initiated from an internal double bond (Δ^<10>) to give 4 and 5, whereas the corresponding sulfone 3b affords terminal cyclization products 16, 17, and 18. The latter product 18 is a mixture of three isomeric olefins (Δ^<7,8>:Δ^<8,9>:Δ^<8,17>=9:4:3). Thus, the cyclization control of ambliofuran analog not only the initiation point but also the termination mode is essential in order to promote the selective total synthesis of (±)-baiyunol (1b), an aglycon of a sweet substance 1a. A furano ketone 3d is the best substrate to our purpose which gives Δ^<8,9> bicyclic product 28 in high yield. The resulting organomercuric ketone 28 is efficiently transformed to 1b, and which is identified with (+)-baiyunol derived from natural sweet glycoside. Glycosidation of (±)-baiyunol is currently undertaken.

著者

山田 英俊 西沢 麦夫

出版者

天然有機化合物討論会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

no.29, pp.349-355, 1987-07-25

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Sweet taste is one of the fascinating field of organic chemistry on the basis of social requirements to find low calorie and high quality taste. Baiyunoside (1) has been characterized as a sweet taste principle of chinese drug, Bai-Yun-Shen (Phlomis betonicoides), by Tanaka and co-workers along with the minor sweet glycoside named phlomisoside I (2). We have designed a general approach to this class of sweet glycosides in order to develop high quality artificial sweeteners. We have already reported an efficient total synthesis of (±)-baiyunol (4), the aglycon of 1 and 2 by means of selective olefin cyclization using mercury(II) triflate/N,N-dimethylaniline complex. We disclose herein the first total synthesis of baiyunoside (1) from (±)-baiyunol (4) via a novel 2' discriminated glycosidation using 2' free glycosyl halide. This novel glycosidation does not accompanied any oligosaccharide formation and this result suggests that very severe steric bulk exist at the newly formed 2' hydroxyl moiety of 6a. As is the case, 6a was entirely inert against a variety of Koenigs-Knorr type glycosidation in order to introduce the xylose moiety. However, Noyori's glycosidation based on a strong affinity between silicon and fluorine was efficiently applied to our purpose. When trimethylsilyl ether 16 was treated with fluorosugar 15 in toluene in the presence of catalytic amount of trimethylsilyl triflate afforded disaccharide 17 and 18 in 38: 62 ratio and in 58% yield. Deprotection of the latter afforded baiyunoside (1) and identified with natural product in every respects. Therefore, we have established a general way to prepare a wide variety of baiyunoside analogs in order to evaluate the taste.