著者

廣瀬 紗弓 戸松 薫 柳瀬 笑子

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 55 (ISSN:24331856)

巻号頁・発行日

pp.PosterP-19, 2013 (Released:2018-03-09)

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1.序論茶(Camellia sinensis)は全世界で愛飲されている飲み物であり、近年の健康志向の高まりとともにその生理的機能が注目されている。カテキン類は茶葉に多く含まれるポリフェノール化合物であり、抗酸化作用、抗がん作用などの様々な生理的機能が見出されている。茶葉中のカテキン類は、紅茶やウーロン茶の製造過程の発酵により酸化、重合し、特徴的なtheaflavinやtheasinensin、oolongtheaninとなることが知られている(Fig.1)。これらにもカテキン類と同等、もしくはそれ以上の生理的機能が期待されているが、含量は非常に少なく分離精製も困難であるが故にその詳細な研究は難しく、また高収率な有機化学的合成法も確立されていない。そこで本研究では、カテキン類の酸化縮合反応の解明を目的として、反応部であるカテキンB環部のモデル化合物を用い、酸化反応について検討した。また、galloyloolongtheanin (1)の合成を目的とし、(-)-EGCg (2)の酸化反応についても検討した。Fig.1 カテキン二量体2.カテキンB環部のモデル化合物を用いた酸化反応 酸化剤としてフェチゾン試薬(炭酸銀-セライト)を用い、5位置換ピロガロール (3)と4位置換カテコール (4)を酸化しtheaflavin類のモデルであるベンゾトロポロン類縁体 (5)を合成した。様々な置換基を持つB環部モデル化合物で反応を行ったところ、5の収率は置換基の種類によって著しく変化した。その原因として、置換基の立体障害や電子供与性が影響している可能性が示唆された。そこで、さらに様々な置換基をもつ3と4を用いて合成を検討したところ、置換基の立体障害による反応性の低下が原因であることが分かった。さらに、5の収率が低い場合において副生成物が確認された。各種機器分析及び誘導化反応の結果、2分子の3が酸化的に縮合した化合物6が生成していることが判明し、6はさらに水と反応してより安定な化合物7となることが分かった。これらの結果から、5の収率低下の原因は、置換基の立体障害による3、4間の反応性の低下による副生成物の生成であることが示唆された(Fig.2)。カテキン類の酸化剤としてはPd/C 1)やK3[Fe(CN)6]2,3)等が知られており、theasinensin A (8)は2をCuCl2で酸化し、アスコルビン酸で還元することで得られることが報告されている4)。そこで、3を同条件で反応させたが、8を部分構造にもつ化合物は得ることができず、6が高収率で得られた。他の酸化剤としてK3[Fe(CN)6]やNaIO3を用いた場合でも同様であり、このことから、3の酸化では実際のカテキン類とは異なる位置選択性を示すことが明らかとなった。Fig.2 カテキンB環部モデル化合物の酸化反応3.(-)-EGCgの酸化反応 1の生成機構を解明するために、2の酸化反応の検討を行った。酸化剤としてPd/CやK3[Fe(CN)6]を用いた場合、8及び9が得られた。CuCl2を用いた場合では、9は得られず、アスコルビン酸で還元することで8が得られた。8が1の生成中間体であると推定しさ(View PDFfor the rest of the abstract.)

著者

安藤 邦雄 佐々木 弘 細川 知良 縄田 喜治

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 18 (ISSN:24331856)

巻号頁・発行日

pp.317-323, 1974-10-01 (Released:2017-08-18)

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Molecular structure and absolute configuration of 4-o-ethyl ascofuranone (C_<23>H_<28>O_5Cl・C_2H_5) were determined by X-ray crystal structure analysis. Crystal structure was solved by the multisolution method. Dihydro-2,2-dimethyl-furan-3-one ring in the molecule adopts an envelope conformation, and the spatial configuration around the asymmetric carbon on the ring is Sinister according to the notation by Cahn, Ingold and Prelog. ORD and CD spectra were consistent with the ketone octant rule which predicted negative Cotton effect for the carbonyl n-π transition. Proton NMR spectra indicated that the ring was rigid, and its conformation in the solution was approximately identical to that in the crystal. All these results are the first stereochemical data on dihydro-2,2-dimethyl-furan-3-one ring in natural product.

著者

山本 恵子 山田 幸子 大田 雅照

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 36 (ISSN:24331856)

巻号頁・発行日

pp.290-297, 1994-09-20 (Released:2017-08-18)

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Hydroxyl groups play a major role in binding to a receptor protein. To clarify the side chain conformation of 1,25(OH)_2D_3 (1) to bind to VDR, we analyzed the mobility of the side chain of 1 and its 20-epimer (2) in terms of the spatial region accessible by the 25-hydroxyl group and the results were displayed as a dot map. The dot map indicates that each vitamin D has two major densely populated regions: A and G for 1 and EA and EG for 2. We designed six 22-substituted analogs of active vitamin D, 3-8, whose side chain hydroxyl is restricted to occupy one of the four spatial regions defined above and the analogs were classified into group A, G, EA, and EG accordingly. Syntheses of analogs, 3-8, were performed via diastereoselective conjugate addition of alkyl cuprate to steroidal (E)-and (Z)-22-en-24-ones (12 and 13) and -22-en-24-oates (16, 17, 20 and 21) as the key step. The activity of the analogs, 3-8, to bind to VDR was examined in compared with 1. It is apparent that the members of A ( 4 and 6) and EG (7) group analogs show much higher activity than the others, G(3, 5) and EA (8). The contrasting activities of the two 22-methyl analogs (3 and 4) are especially outstanding: VDR binding (3:4:1=1/50:1/3:1); differentiation of HL-60 cells (3:4:1=1/70:1:1). The results suggest that the conformation of 1,25(OH)_2D_3 (1) involved in binding to VDR and responsible for activity is the C(17,20,22,23)-anti form and the region where the 25-hydroxyl group occupies is the A.

著者

酒井 浄 石黒 靖尚 舟越 和久 上野 貢嗣 末宗 洋

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 26 (ISSN:24331856)

巻号頁・発行日

pp.299-306, 1983-09-15 (Released:2017-08-18)

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Variously functionalized cyclopentanones are important as starting materials for the synthesis of natural products. We have succeeded in a simple, highly stereospecific synthesis of five membered ring ketone using Wilkinson complex. Thus, the precursors, 1-al-4-enes(4a-e,11,13) prepared in optically active form from D-limonene, (+)-limonen-10-ol and 1-carvone in three steps were submitted for RhCl(PPh_3)_3-catalyzed cyclization in CH_2Cl_2 to afford the cis-3,4-disubstituted cyclopentanones(14-22) in good yield (Table 2). The following results were obtained in this cyclization. 1) In all cases, the cis-3,4-disubstituted cyclopentanones were stereospecifically obtained as the sole products. 2) The cyclization reaction of the six membered lactols(12,13) was found to proceed very slowly even if at high temperature. 3) The cis-3,4-disubstituted cyclopentanones obtained in this method were also found to be applicable for the synthesis of bicyclic ketone(23). 4) The configurations of 3,4-disubstituents in each compounds were clarified by the way of chemical correlation and spectral analyses. Further application for the synthesis of ent-cis,cis-dihydro-nepetalactone(39) will be discussed.

著者

末宗 洋 上野 貢嗣 川原 哲也 小田 晃造 舟越 和久 酒井 浄

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 27 (ISSN:24331856)

巻号頁・発行日

pp.108-114, 1985-09-07 (Released:2017-08-18)

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In the synthesis of natural products consisting of the basic structure of cyclopentane ring, variously functionalized cyclopentanones are required as starting materials. Previously, we succeeded in a simple, highly stereospecific synthesis of the cis-3,4-disubstituted cyclopentanones by the mild reaction with RhCl(PPh_3)_3. By the application of this newer cyclization reaction, we have succeeded in the synthesis of cis,cis-dihydronepetalactone, prostanoic acid, 8-isoprostanoic acid, (+)-brefeldin A and carbacyclin in the optically active form from limonene or Corey lactone. These compounds were synthesized via the following key steps. 1) 3-(3-Oxobutyl)cyclopentanone was easily converted to the deconjugated bicyclic enone (3→4). 2) The regioselective alkylation of limonene was performed by using s-BuLi-TMEDA (1→8). 3) The cis-3,4-disubstituted cyclopentanone from limonen-10-ol could be converted to the trans-3,4-disubstituted cyclo-pentanone by the epimerization (15→16, 22→23).

著者

浜道 則光 藤多 哲朗 松崎 徹 北尾 有紀 城内 正寿 広瀬 良治

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 37 (ISSN:24331856)

巻号頁・発行日

pp.79-84, 1995-09-01 (Released:2017-08-18)

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Mycestericins D (1), E (3), F (2) and G (4), new immunosuppressants, were isolated from the culture broth of Mycelia sterilia ATCC 20349. The immunosuppressive activities of 1 and 2 exhibited an IC_<50> of 16nM and 120nM against mouse allogeneic mixed lymphocyte reaction (MLR), respectively, while 3 and 4 exhibited an IC_<50> of 13nM and 370nM, respectively. The proposed structures were unambiguously confirmed by spectroscopy, chemical evidence and total synthesis. Their absolute configurations have been determined by comparison of their CD spectra with those of synthetic compounds (R and S)-9 prepared from methyl (2S, 4R)-2-tert-butyl-3-formyl-oxazolidine-4-carboxylate (5) and stearoyl chloride. Thus, mycestericins D (1) and F (2) were assigned to be 2 (S), 3 (S) configurations, while mycestericins E (3) and G (4) were 2 (S), 3 (R) configurations. The first total synthesis of mycestericins have been achieved from 5 and 1,8-octanediole (10). The alkyl chain moiety 21 was prepared in 12 steps from 10 by straightforward reactioin. The key intermediate 22 obtained from 5 and 21 could be converted to the desired final compounds. Stereoselective reduction of the ketone 22 with Zn(BH_4)_2 or NaBH_4 provided the (R)-hydroxy 23, the protecting groups of which were removed with 10% MeOH in CF_3COOH, followed by hydrolysis of 24 to give mycestericin E (3). On the other hand, mycestericin D (1) was synthesized from 22 by deprotection, followed by reduction of 25 with Me_4NBH(OAc)_3 and then hydrolysis of 26. Hydrogenation of mycestericin D (1) and E (3) provided the corresponding F (2) and G (4).

著者

藤多 哲朗 浜道 則光 内田 秀治 加治 隆史 松本 範正 広瀬 良治 北尾 郁紀 松崎 徹 千葉 健治

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 38 (ISSN:24331856)

巻号頁・発行日

pp.727-732, 1996-09-02 (Released:2017-08-18)

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2-Aminoalcohol was shown to be the minimum essential structure for the immunosuppressive activity of 2-alkyl-2-aminopropane-1,3-diol, which was generated by modification of ISP-I (1: myriocin, thermozymocidin). 2-Aminoalcohols 4a-h were examined for immunosuppressive activity on mouse allogeneic mixed lymphocyte reaction (MLR) in vitro. The series showed a bell-shaped relationship between the activity and the carbon numbers. Among them, 2-aminohexadecanol (4c) was the most potent. In order to investigate relationship between the activity and the configuration at C-2 in 2-aminoalcohol, (R)- and (S)-isomers of 4c, 2-aminoeicosanol (4h) and 2-amino-4-(4-octylphenyl)butanol (5) were prepared and examined for the activity on mouse allogeneic MLR. As a results, the (R)-isomers were more potent the (S)-isomers, and (R)-4c displayed comparably activity to FTY720 (3), which is expected as a powerful candidate for safer immunosuppressant for organ transplantations and for the treatment of autoimmune diseases.

著者

亀谷 哲治 鈴木 幸夫 伴 千恵子 三沢 薫 高田 信子 叶田 清 本多 利雄

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 29 (ISSN:24331856)

巻号頁・発行日

pp.63-70, 1987-07-25 (Released:2017-08-18)

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Chiral cyclopentane derivatives have widely been employed as important starting materials in the syntheses of naturally occurring compounds. Development of an efficient preparation of a chiral cyclopentane derivative from readly available substances with both (+)- and (-)-forms is therefore desirable. We have established an efficient procedure for the preparation of chiral 2-isopropeny1-5-methyl-4-oxocyclo-pentane-1-carboxylate(1) and (2), whose substituents would be transformed into variety of functional groups, from readily avairable (-)- and (+)-carvone. First, the (-)-isomer(1) was employed in the synthesis of (+)-tecomanine (7), an antipodal form of hypoglycemic monoterpene alkaloid, where the aminylium ion-induced cyclization played an important role. Whereas, N-acetyl-L-acosamine (32), found as a structural component of glycosidic antibiotic, was also derived from the (+)-isomer (2) by utilizing the Beckmann rearrangement and Baeyer-Villiger oxidation as key reactions. Finally, Melillo's lactone(34), a key intermediate for the synthesis of carbapenem antibiotic (+)-thienamycin, was prepared from (-)-isomer(1) by manipulation of its substituents in reasonably high-yield.

著者

チャンサカオ スニー 石川 勉 関 宏子 関根 啓子 岡田 峯明 樋口 義洋 チャイチャンティピュース チャイヨー

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 42 (ISSN:24331856)

巻号頁・発行日

pp.49-54, 2000-10-01 (Released:2017-08-18)

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"Kwao Keur." which had been identified as Puraria mirifica (Leguminosae), has long been used in Thailand and Burma as a rejuvenating folk medicine and has a fascinating history. A potent estrogenic principle has been known to be an unusual phenol miroestrol (1). Although the possible presence of an alternative active component was suggested, there has been no isolation of any other powerful phytoestrogens. with further studies leading instead to the isolation of isoflavonoids. These situation made us re-investigate the estrogenic principles of P. mirifica. The bioassay-guided separation of the ethyl acetate extract of the tuberous roots of P. mirifica by chromatographic techniques resulted in the successful isolation of a new phytoestrogen. (+)-deoxymiroestrol (4). together with (+)-1 and (+)-isomiroestrol (7). The structure of (+)-1 had been determined by X-ray crystallographic analysis and its enantioselective total synthesis was recently reported. Thus. the structure of (+)-deoxymiroestrol (4) was established by comparison of its NMR data with those of (+)-1. The growth-promoting effect of them on MCF-7 human breast cancer cells showed the strongest activity with 4. Interestingly. 4 was easily converted into 1 and 7 by aerial oxidation. suggesting that 4 may be the actual phytoestrogen of P. mirifica. On the other hand daidzein (2), genistein (3), and coumestrol (6) belong to isoflavonoids were isolated as phytoestrogens with lower activity. In addition, it was found that kwakhurin (5). a characteristic isoflavonoid in this plant. also showed the same activity as 2.

著者

吉村 誠司 善光 龍哉 大津 嘉弘 金崎 竜一 重松 伸治 高瀬 茂弘 閨 正博

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 45 (ISSN:24331856)

巻号頁・発行日

pp.281-286, 2003-09-01 (Released:2017-08-18)

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During the course of seeking for novel gluconeogenesis inhibitors, FR225659 and its four congeners were isolated from the fermentation broth of Helicomyces sp. No.19353. Series of NMR analysis allowed elucidation of their planar structures. The planar structure of FR225659 includes a novel acyl moiety, an unprecedented amino acid residue, 3-chloro-4-hydroxyarginine, and two unique amino acid residues, a 3-hydroxy-3-methylproline and a dehydrovaline. As all efforts to obtain crystals of 1 suitable for X-ray crystallography turned out to be in vain, a combination of chemical modification and spectroscopic methods was applied to elucidate the stereochemistry of 1. Acid hydrolysis followed by derivatization with chiral phthalic acid allowed X-ray crystallographic analysis of the proline analogue, which determined its stereochemistry to be (2S, 3R). Conformational analysis of 9 using ^<2,3>J_<CH> developed by Murata et. al. allowed assignment of the relative stereochemistry of the arginine analogue to be 2,3-erythro-3,4-threo. Then, the modified Mosher's method suggested that the absolute configuration of 4'-C is R, which was supported by NOE analysis of 1. The CD spectrum of 1 showed positive Cotton effect at 236nm, indicating an optical activity around the biphenyl axis between the quinoline and the phenol of 1. As the CD spectrum lacking clear Davydov split does not appear to be easy to translate, further elucidation of the axial chirality is now in progress. FR225659 family exerted potent inhibitory activities against glucagon-induced gluconeogenesis of rat primary liver cells, while they showed ten or more times less potent cytotoxicities against EL-4 cell line. As they do not suppress gluconeogenesis independent of glucagon, they should stop a signal pathway from glucagon. Diabetes patients are reported to produce more hepatic glucose than normal, and this leads to complications unless properly treated. Thus, FR225659 family can be drug candidates for diabetes to down-regulate the high blood glucose level of those patients. It is noteworthy that the hydroxyl group at position 3" plays important roles in both biological activities and solubility in various solvents.

著者

加藤 紀元 平馬 清 松村 行雄 吉越 昭

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 23 (ISSN:24331856)

巻号頁・発行日

pp.104-111, 1980-09-10 (Released:2017-08-18)

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Starting from the known keto ester (3), the total synthesis of siccanin (1), a strongly antigerminative mold metabolite produced by Helminthosporium siccans, as well as siccanochromene-E (2), one of biogenetic congeners of the former, has been achieved. The keto ester (3) was submitted to the Robinson annulation with butenone to yield octalone (5), which was then converted into the octaline (8) through the 5-step conventional sequence shown in Scheme 1. After deacetalization of (8), the resultant octalone (10) was isomerized to conjugated enone (11) by treatment with p-toluene-sulfonic acid in methanol, and the latter enone was proven cis-fused by physical and chemical means (Scheme 2). Regioselective hydroxymethylation of the kinetic enolate of 11, followed by methylation with methyl lithium afforded carbinol (25), which was then converted to aldehyde (27) in moderate overall yield (Scheme 3). Diol (28) obtained from 27 in the reaction with lithiated orcinol dimethyl ether yielded, on treatment with pyridinium hydrochloride, tetrahydrofuran derivative (29) in high yield, and the product was then demethylated to monomethyl ether (30) (Scheme 4). While sulfuric acid-induced cyclization of 30 afforded siccanochromene-E methyl ether (31), Lewis acid-catalyzed reaction of 30 gave siccanin methyl ether (32) along with other unidentified products. Demethylation of 32 and 31 were achieved by treatment with sodium ethylthiolate to give 1 and 2 in good yield, respectively (Scheme 5).

著者

吉田 健一郎 東 龍太郎 佐伯 真由子 南 慶典 大谷 敏夫

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 35 (ISSN:24331856)

巻号頁・発行日

pp.250-257, 1993-09-10 (Released:2017-08-18)

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Antibiotic C-1027, a novel antitumor chromoprotein isolated from the broth filtrate of Streptomyces globisporus C-1027, shows extremely potent cytotoxicity against KB carcinoma cells (IC_<50> 0.1ng/ml) in vitro and antitumor activity toward tumor-bearing mice in vivo. These activities are correlated with the ability of the antibiotic to cause DNA double-strand scission. The antibiotic consists of an apoprotein and a labile chromophore (C-1027-Chr) that is responsible for the biological activity of C-1027. The chromophore is readily separated from its apo-protein by extraction, but the exceeding instability in the protein-free state hampered the structure elucidation. The similar situation has been also observed in the other chromoprotein antibiotics of this family such as neocarzinostatin (NCS), macromomycin, auromomycin (AUR), actinoxanthin and kedarcidin. Among them, NCS is the only one whose chromophore structure has been elucidated, and very recently, the structural novelty of kedarcidin chromophore has been disclosed by the Bristol-Myers Squibb group. We have characterized an inactive but more stable reaction product (2) of C-1027-Chr, which was prepared by treatment of C-1027-Chr in ethanol. It possesses a macrocyclic structure together with oxazolinate and aminosugar moieties as side chains. Its benzodihydropentalene core structure suggested to us the presence of an enediyne in the native C-1027-Chr. We disclose herein the novel structure of C-1027-Chr (1) and the cycloaromatization mechanism leading to product (2), which would explain its extreme potency in terms of cytotoxicity and ability to cause DNA double-strand scission.

著者

安元 剛 西上 明則 岡田 泰宏 楠見 武徳 大井 高 安元 美奈 笠井 文絵

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 47 (ISSN:24331856)

巻号頁・発行日

pp.205-210, 2005-09-15 (Released:2017-08-18)

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It has been known that some aquatic organisms change their morphology to defend themselves in response to kairomones released from their predators, although very few kairomones are chemically identified. Scenedesmus, unicellular fresh-water phytoplankton, forms colonies in the presence of its grazer, Daphnia. Hessen and van Donk (1993) discovered the involvement of a chemical substance released from the Daphnia in stimulation of colonies. The addition of filtered medium from a Daphnia magna culture to unicellular Scenedesmus subspicatus achieved within a few days morphological change into 2-, 4-, and 8-colonies, while the controls remained unicellular. Their report has aroused the interest of many scientists to attempt to identify the kairomone, but the chemical substance that triggers this behavior has not been identified. Here we report the identification of the Daphnia kairomones as aliphatic sulfates that cause the morphological change in a unicellular green alga Scenedesmus gutwinskii var. heterospina (NIES-802) at 0.1-1000ng/ml concentrations. The kairomones were synthesized to rule out the possibility that the isolated substances are inactive and they might still be contaminated with a minute amount of 'super active compound'.