著者

磯部 稔 Uyakul D. 高橋 宏幸 後藤 俊夫

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no.31, pp.396-403, 1989-09-17

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Lampteroflavin (1), a riboflavin α-D-riboside was isolated in extraordinary small amount from the luminous mushroom, Lampteromyces japonicus (Fig 1), which was available only two weeks in a year. Extraction method was improved to utilize only alive gills under aeration instead of using the whole body (Fig 3), and the method was established as Scheme 1. It's structure has been elucidated by chromatographic and spectroscopic analyses(1). It's fluorescence spectrum was identical to the bioluminescence spectrum of the mushroom, having maximum at 524nm (Fig 2). We concluded that 1 was responsible to the bioluminescence mechanism as the light emitter, since 1 was only the fluorescent constituent in fresh gills. Previous report that illudin S (lampterol) or ergosta-4,6,8(14),22-tetraen-3-one(2) could be the emitter is thus unlikely judging from the weak fluorescent intensity and the different maximum wavelength from that of mush-room bioluminescence. Lampteroflavin (Table 1) was hydrolyzed with dil. mineral acid to give riboflavin and D-ribose. Riboflavin was identified by HPLC, ^1H NMR, UV, Fluorescence and FAB mass spectrometry. D-ribose was acetylated and then confirmed by ^1H NMR, CD and tandem mass spectrometry. Riboflavin and D-ribose was connected together with α-glycosidic linkage which was determined by ^<13>C NMR of the anomeric carbon (δ=103.2ppm)(3), NOSEY spectrum (H-1" being close to H-3" and H-5') and ^1H NMR pattern of anomeric proton. The total structure of lampteroflavin was confirmed through its chemical synthesis.

著者

岡 希太郎 池 祥雅 木下 仁 原 昭二

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no.15, pp.169-176, 1971-10-01

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The results of the synthetic studies on several steroidal alkaloids of salamander and frog venoms were presented. (1) Cycloneosamandione (VIII) and Cycloneosamandaridine (IX) Recently, the early proposed structure of cycloneosamandione (VI), which had been determined by G. Habermehl with the X-ray diffraction method, has been revised to be VIII on the basis of his own synthetic work. In order to reconfirm this structure, the compound VIII was synthesized by the sequre synthetic sequence. As a result, the physical data of the synthetic specimen were consistent with those of the natural product. Cycloneosamandaridine has been known as one of the minor constituents of the salamander alkaloids. Since this alkaloid has been recognized to have the identical skeleton with cycloneosamandione, the structure, we suppose, should be also revised to be IX from VII. Consequently, we have synthesized the compound IX via the same intermediate 16 as the synthesis of cycloneosamandione (VIII). The identification of our synthetic product with the natural one is now in progress. (2) Batrachotoxin (XI) The synthesis of batrachotoxin has been attempted. The treatment of the hemiacetal 27 with aminoethanol followed by reduction afforded a mixture of 18-hydroxyethylamino steroids (28a and 28b). Then the mixture was converted into the enone 36, which might serve as an useful intermediate for our purpose.

著者

野副 重男 小池 隆 辻 恵美 草野 源次郎 瀬戸 治男 青柳 富貴子 松本 春樹 松本 毅 奥野 智旦

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no.25, pp.282-289, 1982-09-10

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In the course of our continuing investigation of the constituents of a hallucinogenic mushroom, Gymnopilus spectabilis (Japanese name, O-waraitake) collected at Oguni, Yamagata, we have isolated novel type of polyisoprenepolyols designated as gymnopilins -A, -B, and gymnoprenols -A, -B, -C, and -D etc. These substances occured as a mixture of some homologues were separated and throughly purified by means of preparative HPLC and their chemical structures were determined on the basis of the results of oxidative degradation as well as their spectroscopic properties. These polyisoprenepolyols were shown to contain same repeated unit corresponding to hydrated form of usual isoprenoid chain, two or three double bonds and a terminal vicinal diol moiety or the corresponding ester with 3-hydroxy-3-methyl-glutaric acid. The location of double bond was confirmed by the degradation studies. The structures of polyisoprenepolyols such as 1a and 2a have never been encountered in natural products obtained so far. The stereochemistry and biological activities are under investigation.

著者

目 武雄 藤野 明 村井 不二男 鈴井 明男 仏願 保男 西沢 麦夫

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no.50, pp.19-24, 2008-09-01

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Matatabi (Actinidia polygamy Miq., Actinidiaceae) is widely distributed in this country. It is well known from early times that the leaf, the fruit, and the root of this plant show special biological activity in Felidae animals. Although significant chemical studies were carried out, the isolation and structure elucidation of the active principles were not reported until 1959. We isolated two active principles from the methanol extract of the leaf and the fruit of matatabi, a lactone C_<10>H_<16>O_2 named matatabilactone (1), and a base C_<10>H_<13>N named actinidine (2), in 0.0035 and 0.12% yield, respectively. Herein the structure study and the synthesis of 1 and 2 will be discussed.

著者

濱田 季之 松永 茂樹 伏谷 伸宏 藤原 正子 藤田 憲一

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no.37, pp.695-700, 1995-09-01

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A highly cytotoxic polypeptide, polytheonamide B (1), has been isolated from the marine sponge Theonella swinhoei. The structure of polytheonamide B was determined, to be a linear 48-residues polypeptide with the N-terminus blocked by a carbamoyl group, by extensive 2D NMR experiments in DMSO-d_6. The absolute configuration of each amino acid residue was determined by chiral chromatographies of fragment peptides obtained by partial acid hydrolysis of polytheonamide B. Amino acid residues in polytheonamide B have alternating D- and L-configuration. The NMR spectra in CD_3OH/CDCl_3 (1:1) indicated that polytheonamide B adopted certain secondary structure. Conformation analysis was carried out by distance geometry calculations, by DADAS90 program, using NMR parameters obtained in CD_3OH/CDCl_3 (1:1), i.e., a total of 378 distance constraints (160 intra-residue, 96 sequential, 80 long-range NOEs, and 42 hydrogen bonds) and 48 dihedral angle constraints. The calculated structure fit a right-handed parallel β-helix structure, which was proposed for the structure of a pore-forming peptide, gramicidin A.

著者

紺野 勝弘 Picolo Gisele Gutierrez Vanessa Brigatte Patricia Zambelli Vanessa Camargo Antonio C.M. Cury Yara

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no.50, pp.409-413, 2008-09-01

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Snakebite accidents by the South American rattlesnake Crotalus durissus terrificus account for 10% of those occurred in Brazil. It induces severe neurological symptoms, but does not induce pain or severe tissue destruction at the site of inoculation, which is in contrast to the most other snakebites. Due to these properties, the crude venom of this snake used to be employed for controlling pain, for example, of cancer. Recent studies using the crude venom experimentally demonstrated that this venom shows antinociceptive effect more potent than morphine. This effect is orally active and long-lasting for 3-5 days, and despite mediated by opioid receptors, it dose not develop peripheral tolerance nor induce physical dependence unlike morphine. These remarkable properties prompted us to purify and chemically characterize the substance responsible for the analgesic effect. Bioassay-guided fractionation led to the isolation of a novel peptide, designated crotalphine, with a sequence of 14 amino acid residues having a single disulfide bond. We report herein the isolation, sequence determination and synthesis of crotalphine. Pharmacological evaluation using synthetic peptide will also be reported.

著者

広野 巌 大場 茂 斉藤 喜彦 丹羽 治樹 小鹿 一 若松 一雅 山田 静之 松下 和弘

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天然有機化合物討論会

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no.26, pp.9-15, 1983-09-15

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We have examined the constituents of bracken fern, Pteridium aquilinum var. latiusculum and performed fractionation of the boiling water extracts by means of the assay based on carcinogenicity to rats. From the fraction exhibiting carcinogenicity, we have isolated an unstable norsesquiterpene glucoside of illudane type named ptaquiloside (1). The planar structure of (1) has been established on the basis of spectral and chemical means. The carcinogenicity of (1) to rats is currently under investigation.

著者

四津 まり 村田 道雄 安元 健 直木 秀夫

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no.29, pp.240-247, 1987-07-25

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The newt Cynops ensicauda collected in Okinawa, Japan, contained tetrodotoxin (TTX)(1) and its new analogs. Two analogs, compound A and B, were isolated by successive treatment of AcOH extracts on columns of charcoal, BioGel P-2, BioRex70, and Hitachigel 3011C gel. From 3.5kg of the newts 120mg of TTX, 18mg of compound A, and 30mg of compound B were obtained. High resolution FAB mass spectra taken on a JEOL JMS-DX-303HF indicated A to have the same molecular formula as TTX(C_<11>H_<17>O_8N_3) and B to be deoxyTTX (C_<11>H_<17>O_7N_3). ^1H NMR spectra of A showed a high field shift of 11-CH_2 suggested the CH_2OH at C-6 to be axial, 6-epiTTX(2) The axial configuration was further confirmed by NOE measurments. Configuration at C-9 was proved to be the same as TTX. Likewise B was assigned to 11-deoxyTTX(3), and its 11-CH_3 was suggested equatorial as same as TTX. Both 2 and I were in a tautomeric equilibrium between hemilactal (2a,3a) and lactone (2b,3b) forms that were confirmed by NOESY measurments which indicated the saturation transfer between two froms.

著者

田口 貴章 小澤 誠 Kimberley Meriel R. Booker-Milburn Kevin I. Stephenson G. Richard 海老塚 豊 市瀬 浩志

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no.44, pp.235-240, 2002-09-01

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A class of Streptomyces aromatic polyketide antibiotics, the benzoisochromanequinone (BIQs) antibiotics all show trans stereochemistry at C-3 and C-15 in the pyran ring. The opposite stereochemical control is found in actinorhodin (3S, 15R, ACT) from S. coelicolor A3(2) and dihydrogranaticin (3R, 15S, DHGRA) from S. violaceoruber Tu22. A common bicyclic intermediate, which is produced by the early biosynthetic genes encoding a type II minimal polyketide synthase, C-9 ketoreductase (KR), aromatase, and cyclase, was postulated to undergo stereospecific reduction to provide either (S)-DNPA or (R)-DNPA. In the ACT biosynthesis, RED1 encoded by act VI-ORF 1 was proved to reduce C-3 of bicyclic intermediate to determine the 3-(S)-configuration of DNPA. Although the homolog of act VI-ORF 1 was not found in the gra cluster, RED2 was suggested to reduce bicyclic intermediate. An explored RED-2 coding gene, gra-6, was subjected to updated BLAST analysis. The gra-6 product, a putative short-chain alcohol dehydrogenase, has virtually no sequence similarity with RED1. Functional analysis of RED1/2 was made from the following points. 1) Introduction of gra-ORF 6 and gra-ORF 5 under translational coupling (gra-5+6) into the act VI-ORF 1 mutant, S. coelicolor B22, led to ACT-like pigmentation, demonstrating gra-ORF 6 to complement the function of act VI-ORF 1 possibly under unnatural stereochemical control. 2) Combinations of the ketoreductase genes were co-expressed with the early biosynthetic genes required for the bicyclic intermediate formation. gra-ORF6 was essential to produce (R)-DNPA in DHGRA biosynthesis. gra-5+6 led to the most efficient production of (R)-DNPA, implying a possible unique cooperative function as RED2. 3) A series of synthetic analogues was applied to the biotransformations based on ketosynthase-deficient recombinants of S. coelicolor carrying either RED1 or RED2. In all cases for RED1, the β-keto ester substrates were reduced with good to excellent enantioselectivity. However, the simpler substrates were not accepted by RED2, indicating the significant difference in substrate specificity between the two reductases. 4) 3D structures of RED1 and RED2 were predicted based on homology modeling (FAMS) using the templates, L-3-hydroxyacyl-CoA dehydrogenase from human heart (for RED1) and tropinone reductase II (for RED2). Catalytically key amino acid residues were revealed for the both enzymes. 5) RED1 and RED2 were overexpressed in E. coli, and in vitro assay system were successfully established. Optimization of the system, purification of both enzymes and site directed mutagenesis to the suggested key residues are in progress.

著者

柳屋 光俊 続木 一夫 渡辺 隆啓 中島 康之 松田 冬彦 長谷川 和夫 松本 毅

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no.22, pp.635-641, 1979-09-20

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Pederin, a potent insect poison isolated from paedrus fuscipes, exhibits various interesting physiological activities, such as inhibition of mitosis in HeLa cell and blocking of protein synthesis at concentrations of 1-10 ng/me. We describe here the first total synthesis of pederin. Asymmetric Synthesis of Pedaldehyde Derivatives. Asymmetric reduction of ketone 14 was examined under various conditions. The desired alcohol 13R was obtained by reduction with LiAlH_4 in ether-toluene (54: 46) at -123°in 74% e.e. The alcohol 13R was converted stereoselectively to pedamide 28 (Fig. 4,5). Synthesis of N-acyl aminoacetals. A new general method for the synthesis of N-acyl aminoacetals was developed and the method was applied to the synthesis of pederin, starting from (+)-pederic acid and (+)-pedamide.

著者

丸田 聡 山岡 薫 大越 夏実 山下 まり

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no.49, pp.443-448, 2007-08-24

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Tetrodotoxin (TTX) and saxitoxin (STX) bind to a single site in the outer pore of the voltage-gated sodium channels (Na_vs), formed by the amino-acid residues in the outer-pore loops (p-loops) located between the S5 and S6 segments of each of the homologous domain (I-IV) of the a-subunit. Since puffer fish and newts accumulate TTX at high concentration in their tissues, they are thought to have special defense systems against their own TTX. We previously obtained a cDNA encoding Na_v from Fugu pardalis skeletal muscle (fMNa1=fNav1.4a). In fNav1.4a protein, the aromatic amino acid in p-loop region of Domain I in TTX-sensitive Nays was replaced by Asn. Also, Kaneko et al. reported that similar mutation was found in Na_v of retinal neuron of the newt, Cynops pyrrhogaster. In this study, we confirmed that these mutations are responsible to TTX-resistance of puffer fish and newts by evaluation of IC_<50>-TTX values of the corresponding mutants of rNav1.2a transiently expressed in HEK293 cells by electrophysiological study.

著者

竹本 常松 中島 正 横部 哲朗

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no.8, pp.47-52, 1964-10-20

著者

吉田 達彦 豊田 正夫 菅 由紀子 高岡 茂 橋本 敏弘 浅川 義範

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no.38, pp.397-402, 1996-09-02

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Liverworts (Hepaticae) are known to be rich sources of both terpenoids and aromatic compounds with biological activities. The Hepaticae occasionally produce their own peculiar phenolic bis(bibenzyl) derivatives. In the course of our systematic investigation of the chemical constituents of liverworts belonging to the Blasiaceae, we isolated four novel cyclic bis(bibenzyl) dimers, pusilatins A-D (1-4) and two depsides (16, 17) together with nine phenolic compounds (5, 6, 9-15) from Blasia pusilla L. and a novel optically active cyclic bibenzyl-dihydrophenanthrene derivative.(+)-cavicularin (18) from Cavicularia densa Steph. Their structures were characterized by a combination of spectroscopy, X-ray crtstallogarphic analysis and chemical evidences. Further investigation of the phenolic constituents of the thallic liverworts, we isolated a new cyclic bis(bibenzyl) dimer, pusilatin E (8) from Riccardia multifida (L.) S. Gray subsp. decrescens (Steph.) Furuki which was easily derived from riccardin A (7) by coupling reaction using Mn(OAc)_3 ・2H_2O. Previously, we isolated pusilatin D from B. pusilla and proposed the structure (4b) linked by ether C12-O-C1''' bond on the basis of comparison of the ^<13>C NMR data of its acetate with those of the related acethyl compounds. However, the structure (4b) was revised to 4a possessing C10'-O-C11" linkage on the basis of the HMBC analysis. (+)-Cavicularin (18) might be formed by intramolecular phenolic oxidative coupling between 3' and 10' position of riccardin C. On the other hand, riccardin C dimers, pusilatins A-D (1-4) might be biosynthesized by intermolecular coupling between two molecules of riccardin C. These bibenzyl derivatives are significant chemical markers of the Blasiaceae. Pusilatins B (2) and C (3) showed DNA polymerase β inhibitory activity.

著者

黒柳 正典 梅原 薫 柴田 和利 砂山 玲子 遠藤 深春 佐藤 裕子 白須 直美 上野 明

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no.36, pp.9-16, 1994-09-20

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Although much attention has been given to cell differentiation inducers as new types of anti-tumore agent, only a few studies has been reported on differentiation inducers from plant sorces. Therefore, we have searched for naturally occouring substances which induce differnciation of leukemia cells. From Condurango Cortex (Marsdenia condurango) (Asclepidaceae) and Periplocae Cortex (Periploca sepium B.) (Asclepidaceae), many kids of pregnan derivatives and some cardenolides. From withania (Withania somnifera) (Solanaceae) (using Indian market withania and withania cultivated at the medicinal plant garden of this university), more than thirty kinds of withanolides were isolated. From Physalis alkekengi (Solanaceae), physalin and neophysalin derivatives were isolated. Structural elucidation of these 60 kinds of steroid derivatives were carried out by means of spectral methods, especially using NMR spectroscopy including H-H COSY, H-C COSY, HMBC, NOE technics. These steroidal derivatives were tested on cell differentiatio inducing activity against mouse myeloid leukemia (M1) cells. Many kinds steroid derivatives showed the activity. Of these active compounds, some kinds of withanolids, 27, 33, 34 and 35 having 4β-hydroxy-5β,6β-epoxy-2-en-1-one structure of AB ring, showed potent differentiation inducing activity.

著者

大胡 惠明 武内 征司 吉村 寿次

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no.14, pp.101-107, 1970-10-01

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Catalytic asymmetric hydrogenation of benzil was examined by use of bis-dimethylglyoximato cobalt(II)-optically active amine complex. This system gave an extroadinarily high optical yield (50%) never seen before in the case of homogeneous metal complex-catalyzed asymmetric syntheses. The results were summarized as follows. a) Co(DMG)_2 complexes with optically active polyfunctional bases such as quinine, quinidine, cinchonidine, O-acetyl-quinine and brucine resulted in asymmetric hydrogenation, especially amino alcohols were highly effective. However, simple amine could not affect asymmetric induction. b) Increase in the molar ratio of substrate to cobalt or base does not bring about decrease in optical yield, but rather small increase. c) It is worthy to mention that molar equivalent of optically active base is enough to affect asymmetric induction. d) Asymmetric yield increased with increasing polarity of the solvent used. This asymmetric reaction is presumably due to an asymmetry induced on the bis-dimethylglyoxime ring by optically active axial base, provided that this reaction proceeds through the same mechanism as alkyl-Co(DMG)_2B formation from Co(DMG)_2B and olefines under hydrogen atmosphere.

著者

岸 義人 後藤 俊夫 平田 義正 下村 脩

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no.9, pp.60-66, 1965-10

著者

中村 英士 Musicki B. 岸 義人 Morse D. Hastings J. 下村 脩

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no.30, pp.276-283, 1988-09

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The bioluminescence of dinoflagellates involves air-oxidation of luciferin (enzyme substrate) by luciferase (enzyme). On the other hand, Euphausia krills utilize highly fluorescent substance F not only as the catalyst for air-oxidation of a protein but also as the light-emitter. Fluorescent substance F exhibits chemical properties similar to those of dinoflagellate luciferin. Using alumina and ion exchange chromatography at low temperature under inert atmosphere (Sheme 1), the substance F (1) was successfully isolated from Euphausia pacifica. The structure of F was elucidated on the basis of degradation reaction summarized in Fig. 1 as well as the spectroscopic data of F (1) and oxy-F (2). The ring D part of the proposed structure, including relative stereochemistry, was unambiguously established by chemical means; ozonolysis of F, followed by CH_2N_2 treatment, yielded the expected product 7, the structure of which was determined by chemical synthesis. Dinoflagellate luciferin could be isolated from the dinoflagellate Pyrocystis lunula (Scheme 2). The structures of luciferin 8, oxidized luciferin 9 and blue compound 10 were elucidated by comparing their spectroscopic data with those of fluorescent substance F and oxy-F. Dinoflagellate luciferin and krill fluorescent substance F are apparently a member of the bile pigments. To the best of our knowledge, however, these are the first naturally occurring bile pigments, which structurally relate to chlorophylls rather than to haems. Studies on the mechanism of dinoflagellate bioluminescence is in progress.

著者

竹本 常松 高木 信也 中島 正 在原 重信 小池 一弘

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no.16, pp.256-263, 1972-10-01

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A colorless needle crystalline, mp 187-188°(decomp.), C_5H_7O_5N_3 was isolated from Quisqualis Fructus (seeds of Quisqualis indica, and Q. indica var. villosa, Combretaceae), a popular ascaricidal crude drug in China and Japan. The compound was considered to be an unknown acidic amino acid and an active principle. So it was named quisqualic acid after the genus name Quisqualis. The chemical structure of quisqualic acid was consedered to be N^2-L-alanyl-3,5-dioxo-1,2,4-oxadiazolidine(Ia) or N^4-L-alanyl-3,5-dioxo-1,2,4-oxadiazolidine (Ib) on the basis of chemical and spectral data. Therefore Ia and Ib were synthesized by routes shown in the chart 2 and 3, respectively. Ib did not agree with quisqualic acid but Ia was identified with the authentic sample. Thus, the structure of quisqualic acid was confirmed to be N^2-L-alanyl-3,5-dioxo-1,2,4-oxadiazolidine satisfactorily. Quisqualic acid is the first instance of natural compound containing 1,2,4-oxadiazolidine ring.

著者

岩本 理 篠原 涼子 此木 敬一 山下 まり 長澤 和夫

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no.51, pp.181-186, 2009-09-01

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Saxitoxin (STX) (2) and its analogues known as causative agents of paralytic shellfish poisoning, so called PSP, are potent neurotoxins produced by harmful dinoflagellates. This fatal intoxication is attributed to STXs' potent affinity against the voltage gated sodium channels (NaChs), thus the toxins strongly block the influx of sodium ion and inhibit the depolarization process of neuronal cells. We have recently accomplished total synthesis of (-) and (+)-doSTX (ent-2 and 2) and (+)-STX (1) by the use of 1,3-dipolar cycloaddition reaction and unique IBX oxidation reaction. In this paper, we described the NaCh inhibitory activity of novel synthetic STX derivatives 19-22. We also succeeded in developing the new synthetic methodology for constructing the cyclic guanidine skeleton under the extremely mild conditions, which successfully allow us to the total synthesis of (+)-dcSTX (3) and (+)-GTX3 (7) from "protected" saxitoxinol 34.

著者

村上 悌一 芝上 基成

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no.50, pp.617-622, 2008-09-01

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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.