著者

中村 誠宏 森川 敏生 加藤 泰世 李 寧 長友 暁史 池 桂花 大串 輝樹 浅尾 恭伸 松田 久司 吉川 雅之

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.48, pp.535-540, 2006-09-15

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During the course of our characterization studies on bioactive saponins, the saponin fraction from the flowers, seeds of Camellia sinensis and C. japonica were found to show biological activities (gastroprotective, inhibitory effect on serum triglyceride (TG) elevation, and platelet aggregating effects, and so on). Therefore, we tried to isolate various bioactive saponin constituents from Camellia sinensis and C. japonica. 1. Camellia sinensis We have isolated nine new compounds [floratheasaponins A-I] from the flowers, twenty-three new compounds [theasaponins A_1-A_5, C_1, E_3-E_<13>, F_1-F_3, G_1, G_2 and H_1] from the seeds, and six new compounds [foliatheasaponins I-VI] from the leaves of C. sinensis. Floratheasaponins from the flowers were found to inhibit serum TG elevation in olive oilloaded mice. Theasaponins A_2 and E_2 showed inhibitory effects on ethanol-induced gastric mucosal lesions in rat, and their effects were stronger than that of reference compound, cetraxate hydrocholoride. 2. Camellia. Japonica We have isolated nine new compounds [camelliosides A-D, sanchasaponins A-D] from the flowers and six new compounds [camelliasaponins A_1, A_2, B_1, B_2, C_1, and C_2,] of C. japonica. Camelliosides, A and B showed gastroprotective and platelet aggregating effects. In addition, camelliasaponins B_1, B_2, C_1, and C_2 were found to exhibit inhibitory activity on ethanol absorption.

著者

眞岡 孝至 秋元 直茂 藤原 靖弘 橋本 圭二

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.45, pp.611-616, 2003-09-01

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The ripe fruits of paprika (Capsicum annuum L.) is a good source of carotenoids and is used widely as a vegetable and food colorant. The red carotenoids are mainly capsanthin and capsorbin, possessing 3-hydroxy-6-oxo-κ-end group. In the course of the carotenoids studies of paprika, two new carotenoids 1 and 2 were isolated as minor components. The MeOH extract of ripe fruits of paprika (4kg) was saponified with 5% KOH/MeOH, and unsaponifiable matter was chromotographed on silica gel using an increasing percentage of acetone in hexane. The fraction eluted with acetone-hexane (1:9) was subjected to a series of HPLC on ODS with CHCl_3-acetonitrile (1:9) and on silica gel with acetone-hexane (2:8) to yield 1 (2mg) and 2 (0.5mg). The molecular formula of 1 was determined to be C_<40>H_<56>O_2 by HR FAB MS. The positive ion FAB MS/MS spectrum of the molecular ion (M^+) of 1 is shown in Fig 1a. Characteristic product ions of M-111 and M-139 which attributed to cleavage between C-5' and C-6' and between C-6' and C-7', respectively suggested the presence of 6-oxo-κ-end group in 1. The structure of 1 was determined to be 3-hydroxy-β,κ-caroten-6'-one by ^1H- and ^<13>C-NMR, COSY, TOCSY, NOESY, HSQC and HMBC data and named 3'-deoxycapsanthin. The structure of 2 was determined to be 3,4-didehydro-β,κ-caroten-6'-one by HR FAB MS, FAB MS/MS, UV-Vis and ^1H-NMR data. From the CD spectral data and biosynthetic consideration 3R, 5'R and 5'R chiralities were proposed for 1 and 2, respectively. They are the first example of carotenoids possessing 6-oxo-κ-end group.

著者

相見 則郎 高山 廣光 北島 満里子 内田 直喜 須田 真也 大矢 菜穂子 坂井 進一郎 POLZ Leo STOCKIGT Joachim MENDONZA Luis A.

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.33, pp.480-487, 1991-09-07

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The technology of plant cell suspension cultures to generate useful secondary metabolites was emploied for two medicinal plants originally producing the indole alkaloids. I. Biotransformation of Ajmaline in Plant Cell Cultures of Rauwolfia Serpentina Benth. From the methanol extracts of the plant cell suspension cultures of R. serpentina, which have been cultivated in the alkaloid-production medium after feeding of ajmaline (1), three new indole alkaloids, raumacline (2), N_b-methylraumacline (3), and 19(S)-hydroxy-N_b-methylraumacline (4), were isolated. These structures first elucidated by spectroscopic analysis were unambiguously determined by the chemical synthesis from ajmaline (1). These new compounds are the first examples of the macroline-type indole alkaloids having the trans relationship between C15 and C16 positions. II. Isolation of Novel Indole Alkaloids from Cell Cultures of Aspidosperma Quebracho Blanco Schlecht. From the cell suspension cultures of A. quebracho blanco, two novel monoterpenoid indole alkaloids, aspidochibine (19) and 3-oxo-14,15-dehydrorhazinilam (21), were isolated, though the production amounts of them were very low at this stage. The structure elucidation and the stereochemical analysis were made by mainly 2D NMR technique. Aspidochibine (19), which has a characteristic ten-membered lactone, is a completely new structural class of the quebrachamine series.

著者

山口 潤一郎 掛谷 秀昭 庄司 満 長田 裕之 林 雄二郎

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.47, pp.25-30, 2005-09-15

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Lucilactaene (1), a cell-cycle inhibitor in p53-Transfected cancer, is a synthetically challenging molecule because of its rare hexahydro-3a-hydroxy-5-oxo-2H-furo [3,2-b]pyrrol-6-yl ring system and its substituted and conjugated E,E,E,E,E pentaene moiety, which is unstable to acid, base, and light. Lucilactaene (1), which readily undergoes racemization, has been synthesized for the first time in optically pure form via a biomimetic pathway. The conditions under which racemization occurs were elucidated during this total synthesis. The careful isolation of lucilactaene (1) from both the broth and the mycelia under neutral, nonracemizing conditions demonstrated that the isolable natural product is in fact itself racemic. This total synthesis, which enabled verification of the absolute configuration of lucilactaene (1), has several noteworthy features: All the reactions from NG-391 (2) are mild enough not to affect the labile E,E,E,E,E pentaene moiety; ether formation from 2 to 25 and 28 and the intramolecular Michael reaction from 26 to 27 or from 30 to 31 are both highly stereoselective; the reductive removal of the epoxide with Sml_2 without effecting demethoxylation, andthe deprotection of a hemiaminal under neutral, oxidative conditions via vinyl ether 33 by using a newly developed phenylselenylethyl protecting group, are also useful transformations.

著者

森田 桂 小林 栄

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.10, pp.111-117, 1966-09-15

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Lenthionine, a highly sulfur-containing odorous substance, has been isolated from Lentinus edodes (Berk.) Sing [Shiitake Mushroom]. The compound represents the characteristic odor of the mushroom and the structure was established to be 1,2,3,5,6-pentathiepane (1) by physico-chemical measurements. 1,2,4,6-Tetrathiepane (II) and 1,2,3,4,5,6-hexathiepane (III) were also separated from the mushroom in minor quantities. All these cyclic methylene polysulfides from natural source were synthesized from simple starting materials. A precursor of lenthionine was isolated in a crystalline form. The compound was not stable and gradually decomposed into lenthionine and its analogs after being left standing at room temperature. The structure of this precursor (IV) is proposed on the basis of the conventional and high resolution mass spectral studies. Finally, the mechanisms of formation of lenthionine and its analogs from the precursor is discussed.

著者

岡野 健太郎 徳山 英利 福山 透

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.48, pp.175-180, 2006-09-15

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(+)-Yatakemycin (1), which was isolated from a culture broth of Streptomyces sp. TP-A0356, is an antitumor antibiotic that has a characteristic dienone cyclopropane ring found in duocarmycins and CC-1065. Among them, 1 has been shown to exhibit the most potent activity, and therefore has attracted a great deal of attention. The first total synthesis along with the revision of its structure and determination of the absolute configuration has recently been reported by Boger and co-workers. Herein, we describe an efficient total synthesis of 1 utilizing our copper-mediated amination for the construction of all five aryl-nitrogen bonds, allowing us to conduct a sub-gram-scale preparation of 1 in 16% overall yield over 17 steps (longest linear steps from the known starting compound 6). Synthesis of the left segment 3 commenced with dibromination of 6. Removal of the TFA group, and subsequent oxidation provided dihydroisoquinoline 7, which was readily converted to the cyclization precursor 9. The first amination reaction of 9 afforded indoline 10 with retention of the other bromo group. After conversion to the dehydroamino ester 12, the second amination was performed to provide dihydropyrroloindole 13. The Ns group and benzyl ester in 13 were then converted to Fmoc group and a methanethiol ester, respectively. Finally, an Fmoc-directed, regioselective demethylation was performed with BCl_3 to furnish the left segment 3. Our amination also proved to be highly effective for the construction of the middle segment 4. Cleavage of (S)-epichlorohydrin (18) with 2,6-dibromophenyllithium species 17 provided chlorohydrin 19, which was then converted to amination precursor 21. The crucial aryl amination took place smoothly to give tetrahydroquinoline 22. After Mizoroki-Heck reaction with a dehydroalanine derivative 23 and removal of the nosyl group, bromo group was introduced regioselectively. The second amination reaction at the sterically hindered position was achieved by using a stoichiometric amount of CuI to furnish the middle segment 4. The right-hand segment 5 was also prepared in a straightforward manner by using the aryl amination strategy. Three segments thus obtained were assembled to complete the total synthesis. After coupling of the middle segment 4 with the right segment 5, TBS ether 32 was converted into the mesylate 33. Subsequent hydrolysis provided 34, which was subjected to the condensation conditions with 3 without isolation. Two benzyl groups were then removed with BCl_3, in the presence of excess pentamethylbenzene as a scavenger of benzyl cation. Finally, spirocyclopropanation was carried out according to Boger's conditions to furnish (+)-1, which was identical in all respects to the natural product.

著者

下川 賢一郎 岩瀬 賢明 三輪 亮佳 池田 麻理子 大野 修 山田 薫 宮本 憲二 上村 大輔

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.50, pp.487-492, 2008-09-01

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(-)-Ternatin (1) is a highly N-methylated cyclic heptapeptide that was isolated from the mushroom Coriolus versicolor during our continuing search for potential anti-obesity agents from natural resources such as mushrooms. In our previous presentation (2006), we reported the isolation, structure elucidation and synthesis of 1, which potently inhibited fat accumulation against 3T3-L1 murine adipocytes. To clarify the detailed mode of action of (-)-ternatin (1) with regard to fat-accumulation inhibition in adipocytes, we started bioorganic studies of 1 and its analogues. We achieved the solution-phase synthesis of 1 and then evaluated its in vivo biological activity. Treatment with 1 at 5mg/kg/day was found to suppress the increase in body weight and fat accumulation in diet-induced obese mice. Due to the course, a structure-activity relationship (SAR) study of 1 was first investigated aimed at the recognition of the importance of side chain functionalities as well as a suitable site for advanced functionalization in its structure, e.g., biotinylation and introduction of a fluorescent unit.

著者

深井 俊夫 黒田 潤 小西 正隆 野村 太郎 宇野 潤 赤尾 三太郎 来栖 恵二

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.40, pp.461-466, 1998-08-31

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Bacillus polymyxa L-1129 produced a new peptide antibiotic complex, named LI-Fs, composed of more than ten components. In this reports we will describes the isolation, structure elucidation and biological activity of each components, LI-F03a, LI-F03b, LI-F04a, Li-F04b, LI-F05a, LI-F05b, LI-F06a, LI-F06b, LI-F07a, LIF07b, LIF08a and LIF08b. These antibiotics were active against gram positive bacteria, mycobacteria and wide range of fungi and yeast, but not for gram negative bacteria. The antibiotic complex LI-Fs (400mg) was isolated from 10 liters fermentation broth using several kind of column chromatography. HPLC analysis showed that the complex was composed of at least 12 components. The components were isolated by HPLC, and the structures of each components were determined by 1D and 2D NMR and MS spectra coupled with amino acid analyses to be hexadepsipeptide containing 15-guanidino-3-hydroxypentadecanoic acid as side chain. The structure of LI-F05a was identified to be a cyclohexadepsipeptide [L-thr(1)-D-val(2)-L-Ile(3)-D-allo Thr(4)-D-Asn(5)-D-Ala(6)] and LI-F05b was identified as an isomer of LI-F05a that was replaced the Asn residue in LI-F05b with Gln, similar pairs were also found in other components, (LI-F06a-LI-F06b, LI-F07a-LI-F07b, LI-F08a-LI-F08b) (Fig. 4). Four amino acids; L-Thr(1); D-Ala(6); D-Asn(5) or D-Gln(5); D-allo Thr(4) and one side chain were commonly found in the LI-Fs antibiotics. Thus, these moieties seems to be fundamental for biological activity of LI-Fs antibiotics.

著者

野澤 由利子 新井 好史 川嶋 朗 原田 健一

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.48, pp.517-522, 2006-09-15

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The advanced Marfey's method has been developed to nonempirically determine the absolute configuration of primary amine including amino acids and secondary alcohols using liquid chromatography/mass spectrometry (LC/MS) under the reversed phase conditions. In this method, the resolution between the diastereomers derivatized with 1-fluoro-2,4-dinitrophenyl-5-L-leucinamide (L-FDLA) and 1-fluoro-2,4-dinitrophenyl-5-D-leucinamide (D-FDLA) is reflected by the difference of hydrophobicity of the two functional groups at the asymmetric carbon.. However, no effective method has been developed for the estimation of hydrophobicity so far. For this purpose, we introduced log D and applied it to relatively simple primary amines, amino acids and secondary alcohols in the present study. It was found that the difference of the retention times correlated with that of log D for both diastereomers based on experimental results obtained in this study. Furthermore, the method was successfully applied to penicillide. From these results the following procedure is proposed for the non-empirical determination of the absolute configuration of primary amine including amino acids and secondary alcohols: 1) estimate the hydrophobicity by the calculation of log D for two substituent groups at the asymmetric carbon. 2) locate the trans-type arrangement of the two more hydrophobic substituents in the L-DLA derivative and judge the asymmetric carbon to be R or S in the trans-type that is eluted first. 3) derivatize a desired compound with L- or D-FDLA and analyze by LC/MS. 4) compare the elution order with the prospective one and determine the absolute configuration of the asymmetric carbon. The developed method is being applied to more complicated compounds.