著者

釜野 徳明 黒田 直孝 木津 治久 小宮山 寛機

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天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.39, pp.505-510, 1997

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Euphorbia sieboldiana Morr. et Decne. (Euphorbiaceae) is named as "Natsutodai" in Japan and is distributed widely in the mountain field. The roots of this plant are used as a diuretic drug by Japanese people. As regards the constituents of this plant, although over ten of three cyclic diterpenes are isolated by some Chinese groups, no work for biological activities has been reported. Our investigation was undertaken to discover biologically active components of this plant, because the extract showed an inhibition of cell division for fertilized sea urchin egg. In this paper, we report the isolation and structural elucidation of three new jatrophane A type diterpenes, named sieboldianines A(1), B(2), and C(3) (Fig. 2) having the antineoplastic activities, from the CH_2Cl_2 fraction of "Natsutodai" extract by repeated chromatography. Isolation (Fig. 1) was contacted with the two kind of bioassay, which are the inhibition of cell division for fertilized sea urchin egg and the cytotoxicity for human peripheral blood cancer HL-60 cell. Structural elucidation of three new compounds 1〜3 was based on their spectral data such as the infra-red spectra, mass spectra, and especially detail 1D and 2D nuclear magnetic resonance (NMR) spectra(Table 1). From ^1H, ^<13>C NMR data, the jatrophane A skeleton of sieboldianines A(1), B(2), C(3), were reduced, in addition to the presence of two cyclic structures. The 2D HMBC experiment was utilized for established of carbon sequence and two ring condensation. The position of hydroxy esters (-OAc and -OBz) were carefully assigned. Finally, the biogenesis of sieboldianines was discussed (Fig. 3). Also. the strong activities of sieboldianines A(1), B(2), and C(3) for HL-60 cells were indicated in Table 1, together with the interesting activities for the resistant both P388/ADM and P388/VCR cells(Table 2).

著者

中野 真代 小田 真隆 永浜 政博 山本 博文 今川 洋 櫻井 純 西沢 麦夫 樽井 敬史 渋谷 昌弘 大林 寿美代 玉城 翔太

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天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

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vol.54, pp.333-338, 2012

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Vizantine (3) is a synthetic derivative of treharose-6,6-dicorynomycolate (TDCM) which was characterized in 1993 as the cell surface glycolipid of Corynebacterium diphtheriae and shows a variety of significant biological activities for adjuvant development. In vitro, vizantine activates not only the macrophages of mice sera, but also induces the release of MIP-1β, IL-6, IL-8 etc. from human acute monocytic leukemia cell line cells (THP-1 cells). Because almost no TNF-α is induced in vivo, the lethal toxicity to animals was found to be ncredibly low. However, oral administration of vizantine to C57BL/6 mouse (p.o. 100 μg x 7 times) inhibits lung metastasis of B16-BL6 melanoma cells (which are classified in highly metastatic tumor cell). In recent years, structural components of the outer surface membrane of bacteria have attracted considerable attention as lead compounds for adjuvant development. However, a concern of the use of these compounds is that they can over-activate innate immune responses leading to the clinical symptoms of septic shock. Therefore, an important issue is a detailed knowledge of the immunostimulatory mechanism to harness beneficial effects without causing toxicity. Here, to advance the mechanistic studies of vizantine, we have synthesized magnetic beads-attached 4 that maintain immunological activities and can therefore act as a molecular probe. Using a pull-down assay of 4 and the extract of HEK-293T cells transfected with plasmid for TLR4 and MD2, vizantine was found to act as a ligand of the Toll-like receptor 4 (TLR4) and MD2 complex. Furthermore, the macrophage from TLR4 knockout (TLR4 -/-) mice showed decreased response to vizantine, but that from TLR2 knockout (TLR2 -/-) mice did not. Taken together the results suggest that vizantine suppresses the tumor lung metastasis through the activation of macrophages via TLR4/MD2 complex.

著者

森川 敏生 松尾 一彦 八幡 郁子 二宮 清文 村岡 修 中山 隆志

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天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

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vol.56, 2014

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<p>1.はじめに</p><p> ケモカインは,白血球やリンパ球などの免疫担当細胞の細胞遊走を誘導するサイトカインとして広く認識されており,現在までにヒトにおいては50種類近くのリガンドと18種類のシグナル伝達型受容体が知られ,さらに5種類のスカベンジャー/デコイ型受容体も存在する.ケモカインにはよく保存された4つのシステイン残基が存在し,そのうちのN端側の2つのシステイン残基が形成するモチーフにより,CXC,CC,CX3CおよびXCの4つのサブファミリーに分類される.これらのケモカインは免疫応答の制御にとどまらず,アレルギー疾患,自己免疫疾患,感染症やがんの病態発症においても重要な役割を果たしていることが明らかとなっている.近年,種々の疾患の発症や増悪などのキーファクターとなるケモカインおよびその受容体が解明されるにつれ,新たな創薬ターゲットとしてケモカイン受容体アンタゴニストの探索が精力的に展開されている.アレルギー疾患の発症や増悪に関与するケモカイン受容体として,CCR3,CCR4およびCCR8が挙げられる.これらのなかでCCR3は,好酸球の最も主要な遊走制御因子であり,好酸球,好塩基球およびTh2細胞の一部に選択的に発現する (Figure 1).^1,2) </p><p> </p><p> </p><p> 我々はアレルギー疾患をはじめとした難治性炎症性疾患の新たな治療薬シーズの探索研究として,これまでにi.肥満細胞のモデル細胞であるラット好塩基球性白血病細胞(RBL-2H3) を用いた抗原刺激による脱顆粒抑制活性およびTNF-αおよびIL-4産生抑制活性,ii.マウス受身浮腫アナフィラキシー (PCA) に対する抑制作用 (in vivo),iii.マクロファージ様 RAW264.7 細胞を用いたリポ多糖 (LPS, lipopolysaccharide) 誘発一酸化窒素 (NO) あるいはiNOS 発現抑制活性,およびiv. HL-60 細胞由来好中球様細胞からの fMLP (N-formylmethionyl-leucyl-phenylalanine) 刺激による脱顆粒抑制活性,などを指標として検討してきた.³⁾これらの生物活性評価試験において見いだされた天然資源について,単一のケモカイン受容体のみを遺伝子工学的に過剰発現し樹立したケモカイン受容体安定発現細胞株を用い,細胞遊走阻害活性を指標として種々のケモカイン受容体に対するアンタゴニストの探索を行った.その結果,薬用のみならず香辛料として食用にも用いられるメース[ニクズク科(Myristicaceae) 植物Myristica fragrans Houtt. 仮種皮]のメタノール抽出エキスに,CCR3選択的なアンタゴニスト活性を見いだしたことから,その活性寄与成分の探索に着手した.</p><p>2.メタノール抽出エキスのケモカイン受容体アンタゴニスト作用試験</p><p> マウスB細胞株L1.2 細胞を用い各種ケモカイン受容体を過剰発現させた細胞株を樹立し,ケモタキシスチャンバーを用いた細胞遊走抑制作用を指標にアンタゴニスト作用を評価した.すなわち,各発現細胞を細胞遊走バッファー (0.5% BSA,20 mM HEPES pH7.4,RPMI-1640 without phenol red) で洗浄を 2 回行った後,8 × 10⁶ cells/mL となるように懸濁した.リガンドとなるケモカインを細胞遊走バッファーで希釈して下部ウェル</p><p>(View PDFfor the rest of the abstract.)</p>

著者

中村 優一 馬岡 秀陽 上岡 麗子 池田 剛 塚本 佐知子

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天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.52, pp.505-510, 2010

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We reported the structures and biosynthetic experiments of prenylated indole alkaloids, notoamides, which isolated from a marine-derived fungus Aspergillus sp. Among them, notoamides A and B (1 and 2) and stephacidin A (6) contain a bicyclo[2.2.2]diazaoctane ring, which is proposed to be constructed from notoamice E (8) by the intramolecular Diels-Alder (IMDA) reaction. We made a feeding experiment of ^<13>C-labeled-8 in the minimum medium. Contrary to our expectaton, compounds containing a bicyclo ring were not obtained at all. This result suggested that the formation of a pyrane ring would be constructed after the formation of the bicyclo ring. Then, we made a feeding experiment of ^<13>C, ^<15>N-labeled-7, which lacks a pyrane ring in 6. As the result, a pinacol-type rearrangement of the isoprenyl group in 7 occurred to give 11 and 12, and no metabolite containing a bicyclo ring was afforded. Now, feeding experiments of ^<13>C, ^<15>N-labeled-11 and -12 are in progress. Nortoamides O-R (14-17) were isolated from the same extract of the fungus, which yielded other notoamides. Notoamide O (14) possesses a novel hemiacetal/hemiaminal ether functionality hitherto unknown among this family of prenylated indole alkaloids. The structure represents an unusual branc point for the oxidative modification of other members in the family of prenylated indole alkaloids in the biogenetic pathway.

著者

中村 優一 加藤 光 塚本 佐知子

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天然有機化合物討論会実行委員会

雑誌

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vol.53, pp.421-426, 2011

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In our laboratory, we search for drug leads from marine sponge, ascidian and fungus. The extract of the ascidian Didemnum sp., which collected in Indonesia in 2006, showed anti-fungal activity and inhibitory activity of p53-Mdm2 complex formation. p53, tumor suppressor, protein induced growth arrest and apoptosis, and Mdm2 is an E3 for p53 protein. Therefore, inhibition of p53-Mdm2 complex formation is a promising approach for treatment of cancer. Twelve new serinolipids, 1-12 were isolated from Indonesian ascidian Didemnum sp. 1D and 2D NMR spectrum and MS spectrum analysis was revealed the structures of these compounds possessing a 6,8-dioxabicyclo[3.2.1]octane ring, which was appeared in didemniserinolipid A, a glycerophosphocholine moiety and a serinol moiety containing sulfate. Compounds 1-12 demonstrated inhibition of p53-Mdm2 complex formation. Compounds 1 and 5 were the most potent inhibitors with an IC^<50> value of 2.0 μM, while compounds -2 and 10 exhibited weak inhibitors with IC^<50> values of 53 and 55 μM, respectively.

著者

古森 徹哉 瀬戸口 信郎 川崎 敏男

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天然有機化合物討論会実行委員会

雑誌

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vol.10, pp.216-223, 1966

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The unknown, nonsteroidal, nonglycosidal and N-free substance, which had been obtained as crystals from the root tubers of Dioscorea bulbifera L. forma spontanea Makino et Nemoto, was found to be a mixture of at least three compounds. One of them, named bulbiferin C, m.p.255°, (α)_D +17.3°, was isolated only in trace and the structures of major component, bulbiferin B, m.p. 285°, (α)_D+103.0° and minor, bulbiferin A, m.p. 283°, (α)_D +16.2°, were investigated. Bulbiferin B, C_<19>H_<20>O_6, m.w. 344 (mass) has γ-lactone, β-substituted furane and no hydroxyl groups (positive Ehrlich reaction, I.R., U.V. and mass spectra). B is converted to A by hydrolysis with NaOH in pyridine followed by neutralisation and methylation with diazometane. Bulbiferin A,C_<20>H_<24>O_7, m.w. 376 (mass), has hydroxyl, ester, γ-lactone and β-substituted furane functions (Ehrlich reaction, I.R., U.V. and mass spectra). On treatment with NaBH_4 B is unchanged but by catalytic hydrogenation over PtO_2 it gives a hexahydro-compound having tertiary hydroxyl group indicating B (and also A) has an ether oxygen. The hydrogenated B is reduced with LiAlH_4 and the product is subjected to the Se-dehydrogenation to give 1,2,5-trimethyl naphthalene. The N.M.R. spectra of tetrahydro-B and -A indicate the presence of one tertiary methyl group. From these and other experimental data B and A are respectively assigned the partial formulae (a) and (b) of furano-norditerpene type. The results of a further investigation on the location of the functional groups which lead to the tentative structures of B and A are presented.

著者

鈴木 智大 小川 哲弘 阿部 暢男 赤地 拓澄 増田 貴久子 小山 智之 矢澤 一良 河岸 洋和

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天然有機化合物討論会実行委員会

雑誌

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vol.49, pp.383-388, 2007

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Osteoporosis is caused by an imbalance between bone resorption and bone formation, which results in bone loss and fractures after mineral flux. Osteoclast-like multinucleated cells can be differentiated in vitro from co-cultures of mouse bone marrow cells and osteoblastic cells by treatment with osteotropic factors, 1α,25-dihydroxyvitamin D3 (1α,25(OH)_2D_3) and prostaglandin E2 (PGE2). During screening for osteoclast-formation suppressing effects of the extracts of various mushrooms by using the assay, we found very strong activity in the extract of the mushroom Agrocybe chaxingu. Therefore, an attempt was made to isolate the active principles from mushroom and to determine their structures. Powder of the dried fruiting bodies of Agrocybe chaxingu was extracted with CH_2Cl_2, EtOAc and then EtOH. The CH_2Cl_2-soluble fraction only showed the suppressing activity. After repeated chromatography of the fraction, compounds 1 and 2 were purified as the active principles. Osteoclast differentiation was estimated by TRAP-(+) multinucleated cell formation. The addition of compound 1and 2 (3.1μg/ml, 6.8mM) reduced the number of TRAP-(+) multinucleated cells to 66% and 0%, respectively.

著者

田中 正泰 針ヶ谷 弘子 鎌田 樹志 氏原 一哉 橋本 勝 橋本 貴美子 松田 冬彦 柳屋 光俊 白濱 晴久 奥野 智旦

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天然有機化合物討論会

雑誌

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no.34, pp.110-117, 1992-09-10

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Ohwaraitake is Japanese name of a poisonous mushroom Gymnopilus spectabilis and means "a loud laugh mushroom". Accidental ingestion of it causes hallucinosis and abnormal behavior. A hallucinogenic mushroom contains usually psilocybin or its analogues but it is reported that any psilocybin or its congenor does not found in Japanese Ohwaraitake. The toxic symptoms suggest that any neuroexcitatory substance must be contained. The isolation was carried out monitoring depolarizing activity on the new born rat spinal cord. 1. Chromatographical fractionation and bisassay showed that the neuroexcitatory active compounds were gimnopilins (G) which were known as bitter principles of this fungus. Further fractionation revealed that G (1) was inactive and activities of G (2) increased from n=7 to n=5 and besides, G (2), which was newly isolated this time, was more active than G (2). 2. The structure of the new G was determined by the chemical degradation as formula 3. 3. The Chirality of hydroxymethylglutamic acid (HMGA) part was determined as S configuration by the acquisition of (R)-mevalonaloctone through LiBH4 reduction or G (1 and 2). 4. G (2) does not work as an ion carrier probably, since it does not particularly take metal ion from aqueous solution into an organic solvent. 5. Determination of the chirality of tert-alcohols in gymnoprenol (G'), that is, G without HMGA part, was attempted. Eight isomers of the model compounds corresponding to G' (m=2, n=4) were synthesized and were not discriminated by HPLC and NMR. Since two diastereoisomers of MTP-ethoxy-methoxy derivatives of G' (m=1, n=2) were distinguished by ^1H and ^<19>FNMR, these derivatives may be applicable to identification of the synthetic and the natural G'.

著者

原 修 中尾 一成 棚田 喜久 西尾 東 松原 淳 横川 文明 濱田 康正 塩入 孝之

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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

巻号頁・発行日

no.32, pp.617-624, 1990-09-25

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Calyculins having high cytotoxicity were isolated from the marine sponge Discordermia calyx in the Gulf of Sagami. Calyculin A (1), the major cytotoxic constituent, has 15 chiral centers, a spiroketal bearing phosphate, an oxazole ring, and a nitrile conjugated with all (E)-tetraene. However, its absolute stereostructure has remained uncovered. Interestingly, calyculin A (1) exhibits antitumor activity against Ehrlich and P-388 leukemia in mice. Its unique complex structure as well as its intriguing biological activity led us to investigate the total synthesis of 1, which will determine the absolute configuration of 1 as well. Retrosynthetic analysis has revealed that 1 would be constructed from four fragments A, B, C, and D, shown in Chart 1. Fragments A and B could be prepared by stereoselective reduction of tetronic acid derivatives 11 and 24, respectively. Fragments C and D were prepared from amino acids utilizing the methodology developed by us earlier.

著者

泰地 美沙子 山崎 俊正 河原 一樹 元岡 大祐 中村 昇太 豊島 正 大久保 忠恭 小林 祐次 西内 祐二

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天然有機化合物討論会実行委員会

雑誌

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vol.53, pp.199-204, 2011

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Marinostatin (MST) isolated from a marine organism is a serine protease inhibitor consisting of 12 amino acids with two internal ester linkages formed between the β-hydroxyl and (β-carboxyl groups, Thr^3-Asp^9 and Ser^8-Asp^<11>. MST was synthesized by regioselective intramolecular esterification employing two sets of orthogonally removable side chain protecting groups for Ser/Thr and Asp. SAR study revealed that the ester linkage with Thr^3-Asp^9, the cis-conformation at Pro^7 and the N-terminal Phe^1-Ala^2 are the structural requirements for expression of the inhibitory activity. These findings were also supported by analyzing the solution and enzyme-bound structures of MST. Of particular note is that cis-Pro^7 may promote the internal hydrogen bond between the NH proton of Are and the carbonyl oxygen atom of the ester linkage with Thr^3-Asp^9 to protect its scissile bond of Met^4-Arg^5. This could be responsible for enhancing the potency. To elucidate the importance of backbone conformation at position 7, 16 and cis/trans-olefin analogs 17/18, in which cis/trans-olefins are substituted for the amide bond of Tyr^6-Ala^7, were synthesized. Although Ala^7 in 16 takes a trans-conformation in the solution structure, it takes a cis-conformation in the enzyme-bound structure. This implies that Ala^7 would isomerize from a trans to cis conformation when it binds to an enzyme, resulting in a certain inhibitory potency. However, the trans-olefin analog 18 lost the potency while the cis-olefin analog 17 displayed almost the same potency as that of MST. These results clearly indicated that the cis-conformation at position 7 is indispensable for binding to an enzyme in a canonical manner. By applying the structural motif of MST, we were able to rationally design protease inhibitory specificities that differed from those of the natural product.

著者

早川 謙二 麻生 和義 大薄 悟 兼松 顕

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天然有機化合物討論会実行委員会

雑誌

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vol.30, pp.387-394, 1988

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Intramolecular cycloadditions of Allenes constitute the versatile methods for the stereocontrolled synthesis of variously functionalized polycyclic compounds. Especially, intramoleclar Diels-Alder reactions using allenic dienophiles can full enjoy the merits of the unique structure of allens and proceed with extraordinary ease. On the basis of this strategy, several new synthtic methodologies were developed; (1) the intramolecular Diels-Alder reaction of allenyl ethers followed by hydration andoxidation provided a new polycyclic lactone synthesis (Scheme 1). This method was successfully applied to the total synthesis of platyphyllide 30(Scheme 5). (2) The allenyl ether bearing a substituent at C-2 position (ex.,1c,1d) underwent the tandem [2+2] cycloaddition and [3,3] sigmatropic rearrangement to produce the novel product having an bicyclo [n.3.11 carbon ring system (ex., 5c, 5d) (Scheme 2).

著者

内田 有紀 杉村 秀幸

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天然有機化合物討論会実行委員会

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vol.46, pp.425-429, 2004

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Arohynapenes are new anticoccidial agents, isolated from the fermentation broth of Penicillium sp. FO-2295 strain and their structures have been proposed as shown in Fig. 1. Although the absolute stereochemistry of arohynapenes are unclear, in comparison with the spectral data of an analogous natural product, tanzawaic acid A, the relative stereochemistry of arohynapene B is deduced to be cis. In this study, we planed the total synthesis of racemic arohynapene B starting from cis-3,5-dimethylcyclohexanone in order to confirm its relative stereochemistry. Treatment of cis-3,5-dimethylcyclohexanone (2), prepared from 3,5-dimethyl-2-cyclohexen-1-one (1) via stereoselective hydrogenation (H_2, Pd/C), with ethynylmagnesium bromide, followed by acetylation gave propargyl acetate derivative 3. Acetate 3 rearranges in benzene containing a catalytic amount of silver trifluoroacetate under reflux to afford 1,3-dienyl acetate 4, which underwent Diels-Alder reaction with dimethyl acetylenedicarboxylate. After heating in toluene under reflux for four days, the reaction mixture was treated with DBN to provide tetrahydronaphtalene-dicarboxylate derivative 5. With the tetrahydronaphthalene skeleton in hands, we next focused the elongation of the dienylcarboxylic acid side chain. After reduction of diester 5 with LAH, selective protection of the 2-hydroxymethyl group in diol 6 was investigated. Moderate selectivity was observed when TBSCl-imidazole/DMF was used for the protection condition. Oxidation of the remaining hydroxy group to aldehyde, followed by Horner-Wadsworth-Emmons reaction gave unsaturated ester 9, which was subjected to reduction, oxidation and HWE reaction afforded protected arohynapene B. Finally, hydrolysis of the ester moiety, followed by cleavage of the silyl ether under mild acidic condition furnished (±)-arohynapene B.

著者

矢原 正治 金城 順英 下川 隆志 野原 稔弘 山原 條二 千坂 武司

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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.27, pp.726-733, 1985-09-07

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We have examined the constituents of three crude drugs showing an antihypercholesteremic activity. 1) Daemonorops draco --- D-7 was obtained as an active substance. It was further separated into two compounds (D-7-I,II) being the isomers each other and their substances were deduced to be the deoxy-proanthocyanidins by the spectral data. 2) Caesalpinia sappan --- Total nineteen compounds relating to brazilin were isolated and the chemical structures of fourteen compounds among them were discussed by the spectroscopic means. SO-k, g,e were the 3-benzyl-chroman-4-one derivatives; SO-i,b,c were shown to be the first examples of the 3-benzyl-chroman-4-ol derivatives and assumed to be the key-intermediates on the biogenetic route of brazilin; All of SO-j,p,SLC-b,c,d presented new novel framework-models among the naturally occurring compounds. SO-j was suggested to be produced from SO-i,b,c by oxidative coupling, SO-p was presumed to be derived from brazilin by oxidative fission. SLC-b,c,d were considered to be originated from brazilin. SLC-b was effective for antihypercholesteremia. 3) Dalbergia odorifera --- Five aromatic compounds, DO-I-V, were isolated from the active fraction and their structures were revealed to be the unique bi-isoflavanoids by the various spectral data.

著者

杉山 重夫 本田 昌徳 古森 徹哉

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天然有機化合物討論会実行委員会

雑誌

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vol.31, pp.22-29, 1989

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In our study on the isolation and structure elucidation of biologically active compounds from marine invertebrates, we synthesized the four diastereomers of C_<16>-phytosphingosine (10, 12, 25, and 26), acanthacerebroside A (1), and D-galactosylceramide (3b) as described below. (2S, 3S)-Allylic alcohol, which was prepared from the L-serine derivative and the (E)-vinylalane compound, was converted into (2S, 3S, 4R)- and (2S, 3S, 4S)-phytosphingosines by epoxidation, DIBAH reduction, and debenzylation. The same treatment of (2S, 3R)-allylic alcohol gave (2S, 3R, 4R)- and (2S, 3R, 4S)-phytosphingosines. (2R)-Acetoxytetracosanoic acid was prepared and coupled to (2S, 3S, 4R)-phytosphingosine to give the ceramide (34). Glycosylation of 34 gave the desired monoglycoside (36) and the bisglycoside (37). 36 was converted into 1 by deacetylation. New D-galactosylceramides were isolated from Chondropsis sp., but the absolute stereochemistry has not been determined. Therefore, (2S, 3S, 4R, 6E)- and (2R, 3R, 4R, 6E)-phytosphingosines were prepared via asymmetric epoxidation. The former was transformed to (2S, 3S, 4R, 6E, 2'R)-D-galactosylceramide and its heptaacetate. The spectral data of them were in excellent agreement with those of the natural specimens.

著者

上原 忠夫 大沼 俊雄 鈴木 赳 加藤 忠弘 吉田 利男 高橋 勝宏

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.22, pp.235-242, 1979-09-20

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From a higher boiling fraction (Bp>100℃/8 Torr) of peppermint oil (Mentha piperia L.) was isolated a white crystalline (mp 59-61℃, 300 mg from 80 g of the fraction) having a molecular formula of C_<15>H_<24>S. The structure of the crystalline was unequivocally determined by X-ray crystallographic analysis and we named it mintsulfide (1)(abbreviated as MS). Ultraviolet irradiation (Pyrex filter) of (-)-germacrene D (2)(abbreviated as GD), one of the major components of the oil, in the presence of sulfur powder afforded the mintsulfide (1), thus demonstrating the absolute configuration of MS. The mintsulfide was converted into the isomer (4). Both 1 and 4 were oxidized to give the products (5〜10), which showed the chemical shifts in the NMR spectra as summarized in table 1 and 2. Table 3 indicates the results of photochemical conversion of GD (2), giving MS (1) and/or β-bourbonene (3) under the various conditions. The evidence in table 3 suggests that activated sulfur (sulfur atom ?) is generated first under the Pyrex filtered irradiation. The activated sulfur reacts with GD, leading the formation of MS (1). This novel photoreaction is substrate specific since presence of caryophyllene (12) or β-bourbonene (3) affects no influence. The preliminary experiments revealed that myrcene (13) and tenmembered diene (14) also react with the photo-activated sulfur.

著者

津田 恭介 生熊 晋 河村 正朗 太刀川 隆治 馬場 義彦 宮寺 哲男

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.6, pp.28-32, 1962

著者

アウン ニン・タンダ 二改 俊章 小森 由美子 野々垣 常正 高谷 芳明 丹羽 正武

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.52, pp.607-612, 2010-09-01

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Monpanoki (Argusia (or Messerschmidia or Tournefortia) argentea (Boraginaceae)) is locally used in Okinawa in Japan as an antidote for poisoning from snakes venoms, Trimeresurus flavoviridis (habu). A methanolic extract of the plant significantly inhibited hemorrhage induced by crude venom of Trimeresurus flavoviridis. The extract was then separated according to antivenom activity by using silica gel (ODS) column to afford rosmarinic acid (RA) (1) as an active principle. RA (1) significantly inhibited the hemorrhagic effect of crude venoms of T. flavoviridis, Crotalus atrox, Gloydius blomhoffii, Bitis arietans as well as snake venom metalloproteinases, HT-b (C. atrox), bilitoxin 2 (Agkistrodon bilineatus), HF (B. arietans), and Acl-proteinase (Deinagkistrodon acutus). This is the first report of the antihemorrhage activity of RA (1) and RA (1) greatly contributes to the antihemorrhagic efficiency of this plant against crude snake venoms and hemorrhagic toxins. Furthermore, mechanistic evidence of RA's neutralization of the hemorrhagic effects of snake venom was invesitigated. Inhibitions against fibrinogen hydreolytic and collagen hydrolytic activities of T. flavoviridis venom were examined by SDS-PAGE. Histopathological study was done by using microscope afer administration of venom with or without RA. RA was found to markedly neutralize venom-induced hemorrhage, fibrinogenolysis, cytotoxicity and digestion of type IV collagen activity. Moreover, both hemorrhage and neutrophil infiltrations were inhibited by RA, although both were observed in pathology sections administered only T. flavoviridis venom. These results demonstrate that RA inhibited most of the hemorrhage effects of venom. These findings indicate that rosmarinic acid can be expected to provide therapeutic benefits in neutralization of snake venom accompanied by heat stability.

著者

村上 悌一 芝上 基成

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.50, pp.617-622, 2008

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Sphingofungins (A-F) are a family of antifungal metabolites produced by microorganisms, and have been shown to be potent and specific inhibitors of serine palmitoyl transferase, an essential enzyme for the biosynthesis of sphingolipids. These compounds have a lipid tail and a polyhydroxy-amino acid head moiety with four contiguous chiral centers and a trans-olefinic function. Due to their biological activity and structural complexity, the sphingofungins have inspired a number of synthetic efforts. We report here a novel synthetic approach to sphingofungins using D-gluconolactone as a chiral source of the head moiety. Gluconolactone 1 was converted to 2-azido-mannonate derivative 3, from which C5-aldehyde derivative 4 was readily prepared. The hydrophobic portion containing (R)-hydroxy group was prepared via asymmetric transfer hydrogenation of pentadec-8-yn-7-one 13. The resulting pentadec-1-yn-9(R)-ol derivative 15 was converted to pentadec-1(E)-enyl-zinc derivative 17, which was reacted with the C5-aldehyde 4 to give separable diastereomeric adducts (7:1). The major adduct was deduced to be natural C5-(S)-alcohol 18, a key intermediate for the synthesis of sphingofungins A-D. Acidic hydrolysis of 18 gave the azide-lactone 19, and the azide was reduced with zinc in acetic acid to give the amine 20. When the reduction was carried out in the presence of acetic anhydride, the acetamide 21 was obtained. Mild basic hydrolysis of 20 and 21 afforded sphingofungins B and D, respectively.

著者

藤岡 稔大 岩元 雅代 岩瀬 由紀子 八山 しづ子 岡部 光 三橋 國英 山内 辰郎

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.30, pp.165-172, 1988

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Dammarane-type triterpene glycosides, named actinostemmoside A, B, C, D, G and H, baccharane-type triterpene glycosides, actinostemmoside E and F, and oleanane-type triterpene glycosides, lobatoside A, B, C, D, E, F, G and H were isolated from the herb of Actinostemma lobatum MAXIM. (Cucurbitaceae). Their structures were elucidated on the basis of the spectral and chemical evidences as shown in the text. The structure of actinostemmoside F was elucidated mainly on the basis of two dimensional-incredible natural abundance double quantum transfer experiment (2D-INADEQUATE) spectrum. Among dammarane-type actinostemmosides, D is the glycoside of the first naturally occurring dammarane having the (20R)-configuration, and actinostemmosides E and F are the second baccharane-type triterpene glycosides isolated from the natural source. Lobatoside B, C, D, E, F and G are cyclic bisdesmosides similar to tubeimoside I isolated from the tuber of Bolbostemma paniculatum (MAXIM.) FRANQUET. (Cucurbitaceae), and this is the second instance of the isolation of cyclic bisdesmoside from the plant kingdom.

著者

川松 豊 杉原 弘貞 佐々木 希吉 森本 浩

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.13, pp.99-106, 1969-09-01

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I. Synthesis of 2,3-dialkoxy-5-alkyl-1,4-benzoquinone a) 4a and 4b obtained from 1 were oxidized with organic peracids to give 2,3-dimethoxy-(5a) and 2,3-diethoxy-5-methyl-1,4-benzoquinone (5b). b) 9a and 9b obtained from 6 were oxidized in a similar manner to give 5a and 10. II. Synthesis of isoprenoid quinones The authors found two new condensation methods. a) Method using an N-sulfinylamine. A solution of hydroquinone (12), methyl N-sulfinylanthranilate (14) and phytol (13) in dioxane was heated and oxidized with ferric chloride to give 2,3-dimethoxy-5-methyl-6-phytyl-1,4-benzoquinone (15) as well as by-products 16 and 17. The structures of 16 and 17 were made clear and the reaction mechanism was discussed. The results are shown in Table 1. b) Method using a metal. A solution of 5a and X-CH_2-CH=C-CH_3-CH_2-R in petroleum ether was treated with slightly an excess amount of amalgamated zinc at the room temperature to give 18. The product 18 was obtained also from hydroquinone (12). The reaction mechanism and the results are shown in Table 2. III. Stereochemistry of isoprenoid quinones It has been so far known that the steric configuration of the side chain of naturally occurring isoprenoid quinones is all-trans, but synthesized isoprenoid quinones inevitably contain a small amount of the cis-isomer. Then, the authors separated these isomers by the column chromatography to confirm their yields and to compare their NMR spectra with each other. The relationship between the structures of the quinones and the biological activity is also mentioned.