著者

小倉 治夫 伊藤 常男 岡本 孝 大村 智

出版者

公益社団法人日本薬学会

雑誌

Chemical & pharmaceutical bulletin (ISSN:00092363)

巻号頁・発行日

vol.17, no.4, pp.844-846, 1969-04-25

著者

大村 智 中川 彰 鈴木 数広 秦 藤樹 Jakubowski Ann Tishler Max

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.17, pp.229-236, 1973

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We have been studied the relationship between the structures and the biological activities on 16-membered lactone ring macrolide antibiotics. The aglycone moiety from 16-membered macrolides has not been reported, but in the present series of work, we have chemically obtained the aglycone from leucomycin A_3 (LM A_3) (I). Treatment of (I) with m-chloroperbenzoic acid in CHCl_3 gave the N-oxide (II), which was refluxed with Ac_2O in CHCl_3 to obtaine aglycone, leuconolide-A_3 5,18-hemiacetal (III). In the above reaction, a neutral macrolide, 2'-acetyl 3'-desdimethylamino 3'-oxo LM A_3 (X) which 3'-dimethylamino group on mycaminose moiety was converted to ketone carbonyl was isolated from the same reaction product. Furthermore, (I) was reacted with Al-isopropoxide to give 9-dehydro 18-dihydro leucomycin A_3 (V). (V) was oxidized with m-chloroperbenzoic acid to N-oxide (VII), and(VII)was then treated with Ac_2O in CHCl_3 to obtain 9-dehydro 18-dihydro leuconolide-A_3 (VIII). In order to clarify the correlation between the structure and biological activity of mycaminose moiety, various derivatives were synthesized. The antimicrobial activities of the both glycone, (III) and (VIII) completly disappeared, and it was found that the decreasing of electro-density on dimethylamino group on mycaminose moiety resulted in the decrease of the activity.

著者

大村 智 粟谷 寿一

出版者

公益社団法人 日本油化学会

雑誌

油化学 (ISSN:0513398X)

巻号頁・発行日

vol.28, no.2, pp.75-80, 1979

著者

大村 智

出版者

公益社団法人 日本農芸化学会

雑誌

化学と生物 (ISSN:0453073X)

巻号頁・発行日

vol.12, no.11, pp.787-794, 1974

被引用文献数

1

著者

岩井 譲 志水 秀樹 大村 智

出版者

公益社団法人 日本農芸化学会

雑誌

化学と生物 (ISSN:0453073X)

巻号頁・発行日

vol.23, no.6, pp.379-385, 1985

被引用文献数

1

著者

秦 藤樹 大村 智 片桐 通子 小倉 治夫 納谷 恵三 阿部 仁之助 渡辺 哲夫

出版者

公益社団法人日本薬学会

雑誌

CHEMICAL & PHARMACEUTICAL BULLETIN (ISSN:00092363)

巻号頁・発行日

vol.15, no.3, pp.358-359, 1967

被引用文献数

8

著者

大村 智 中川 彰 関川 賢二 小谷 勝 秦 藤樹

出版者

公益社団法人日本薬学会

雑誌

CHEMICAL & PHARMACEUTICAL BULLETIN (ISSN:00092363)

巻号頁・発行日

vol.17, no.11, pp.2361-2363, 1969

被引用文献数

14

著者

大村 智 中川 彰 竹嶋 秀雄 宮沢 淳 渥美 清夫 Piriou F. Lukacs G.

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.19, pp.434-441, 1975

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According to previous reports, the aglycone carbons of the 16-membered macrolide antibiotic, magnamycin A, 1 are derived from nine acetates, one propionate and one methionine as shown in Fig. 1. As an application of a recent systematic ^<13>C-NMR study of 16-membered macrolide antibiotic, the validity of these investigation was reexamined on leucomycin A_3 2 which is structurally similar to magnamycin A. It was found that carbons-5, -6, -17 and -18 of leucomycin A_3, 2 were derived from butyrate and carbons-3 and -4 on the aglycone arose from outside of acetate contrary to the proposal in the study on magnamycin biosynthesis. Although the origin of the carbons-3 and -4 is not yet known at present time, this finding let us to investigate the origin for the carbons-3 and -4 of the aglycone of tylosin which has different carbon skeleton from leucomycin or magnamycin (Fig. 3). Consequently, the metabolic origin, acetate, propionate and butyrate was proposed as shown in Fig. 5. The addition of [1-^<13>C]butyrate to a fermentation medium of tylosin showed the enrichment for carbons-3, -7, -11, -13 and -15 of aglycone as like as carbon-5 which is predicted to be enriched by the precursor. On the other hand, carbons-4, -8, -12, -14 and -16 were enriched as like as carbon-19 by [4-^<13>C]2-ethylmalonate. The metabolic pathway is not yet clear, however these precursors are thought to be partially incorporated to the aglycone of tylosin via propionate.

著者

大村 智

出版者

公益社団法人 日本農芸化学会

雑誌

化学と生物 (ISSN:0453073X)

巻号頁・発行日

vol.8, no.3, pp.139-150, 1970

著者

船山 信次 中川 彰 大村 智

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.28, pp.73-80, 1986

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During the cource of our screening program for new antibiotics, herbimycin C (1), trienomycins A (6), B (7) and C (8). awamycin (9) and hitachimycin (stubomycin) (10) were isolated and characterized. Each antibiotic except for 10 possesses macrocyclic lactam structure containing benzenoid or naphthalenoid moiety as a chromophore. Structures 1 and 6-9 were elucidated mainly through the comparative NMR analysis with the known ansamycin antibiotics and the structure of 10 was established by the chemical degradations. Further, "Celmer's model" which was applied to the stereochemistry and biogenecis of macrolide antibiotics was applied to those of ansamycin antibiotics such as macbecin I (14). naphthomycin A (15). rifamycin B (16) and streptovaricin C (17) in which the absolute configurartions have been established. Consequently, the absolute configurations of herbimycin A (2) and 9 except for C-6 and C-7 were proposed as shown in Fig. 2. through the model.

著者

大村 智 大岩 留意子

出版者

学会出版センタ-

雑誌

化学と生物 (ISSN:0453073X)

巻号頁・発行日

vol.20, no.1, pp.p10-12, 1982-01

著者

大村 智 供田 洋

出版者

公益社団法人 日本油化学会

雑誌

油化学 (ISSN:0513398X)

巻号頁・発行日

vol.34, no.1, pp.2-9, 1985

著者

大村 智 中川 彰

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.20, no.12, pp.1226-1232, 1984

著者

大村 智 田中 芳武 増間 碌郎 儘田 弘

出版者

日本醗酵工学会

雑誌

日本醗酵工学会大会講演要旨集

巻号頁・発行日

vol.57, pp.106-107, 1982

著者

大村 智 竹嶋 秀雄

出版者

公益社団法人 日本農芸化学会

雑誌

化学と生物 (ISSN:0453073X)

巻号頁・発行日

vol.15, no.7, pp.447-453, 1977

被引用文献数

1

著者

大村 智

出版者

公益社団法人 日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.106, no.9, pp.729-757, 1986

被引用文献数

2

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After structure elucidation of 16-membered macrolide antibiotic leucomycin, the structures of spiramycin, tylosin, megalomicin, irumamycin and virustomycin were determined by chemical degradation and nuclear magnetic resonance (NMR) spectroscopy. The studies on the chemical modification and structure activity correlation of macrolides led to the elaboration of clinically useful new derivatives.<BR>The biosynthetic origin of the carbon skeletone of macrolide aglycone was investigated by means of <SUP>13</SUP>C NMR and the feeding experiments of <SUP>13</SUP>C labeled precursors. We found that an antifungal antibiotic cerulenin is a specific inhibitor of fatty acid and &ldquo;polyketide&rdquo; biosyntheses, and applied the antibiotic to the biosynthetic studies of macrolides after formation of the lactone ring and to the production of a new &ldquo;hybrid&rdquo; macrolide, chimeramycin. Furthermore, a strain which produces a new &ldquo;hybrid&rdquo; antibiotic mederrhodin was breaded from actinorhodin and medermycin producers by gene manipulation.<BR>Sixty five or more new antibiotics have been discovered from secondary microbial metabolites using newly devised screening systems. Azureomycins and izupeptins were found as bacterial cell wall biosynthesis inhibitors. In combination with the above screening, several new antibiotics, nanaomycins, frenolicin B, cervinomycins, asukamycin and so on were discovered as antimycoplasmal substances. Diazaquinomycins as antifolate substance, hitachimycin and avermectin as anthelmintics, herbimycin, phosalacine and oxetin as herbicids have been found by the corresponding each screening system. The structure elucidation, biosynthesis and mode of action of these antibiotics have been studied. Among of them, nanaomycin A and avermectin (or ivermectin) have been employed as antifungal and antiparasitic therapeutics, respectively, for veterinary use.

著者

柘植 尚志 西村 正暘 大村 智 甲元 啓介 尾谷 浩

出版者

日本植物病理學會

雑誌

日本植物病理学会報 (ISSN:00319473)

巻号頁・発行日

vol.51, no.3, pp.277-284, 1985

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宿主特異的毒素を生成する<i>Alternaria alternata</i>群植物病原菌の病原性発現および分生胞子発芽時の毒素生成に及ぼす化学物質の効果について検討した。ナシ黒斑病菌分生胞子懸濁液に,抗生物質セルレニンまたはメチオニンをそれぞれ20ppm, 100ppm以上の濃度で添加すると,胞子の発芽,付着器形成などは殆んど影響されなかったが,胞子発芽時の宿主特異的毒素(AK-毒素)の生成・放出は著しく抑制された。また二十世紀ナシ葉に対する病原性の低下が観察された。さらに,これらの化学物質は,リンゴ斑点落葉病菌のAM-毒素生成およびイチゴ黒斑病菌のAF-毒素生成も阻害し,両菌の病原性低下を引き起こした。また,KH₂PO₄, NH₄Cl,酵母エキスおよびシステインも,ナシ黒斑病菌の胞子発芽にはほとんど影響することなく胞子発芽時のAK-毒素生成能力および病原性を阻害した。しかし,これらの化学物質の効果は,セルレニンやメチオニンほど顕著ではなく,比較的高濃度処理によって,阻害効果が認められた。以上の結果から,<i>Alternaria alterrata</i>群病原菌の分生胞子懸濁液に,ある種の化学物質を添加することにより,胞子発芽時の宿主特異的毒素生成が阻害され,その結果,病原性の低下が引き起こされるものと考えられ,本群菌の病原性発現における胞子発芽時の宿主特異的毒素の重要性が示唆された。

著者

今村 信孝 今井 美光 三浦 聡美 中川 彰 大村 智

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.308-315, 1988

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A new antibiotic, phthoramycin (1; C_<40>H_<68>O_<12>) which exhibits antimicrobial activities against fungi such as the plant pathogen Phytophthora parasitica was isolated from the cultured broth of a strain of Streptomyces sp. The structure and biosynthetic origin of 1 were elucidated by the 2-D NMR spectral experiments of pentaacetylphthoramycin (2) in combination with biosynthetic means using [1-^<13>C]- and [1,2-^<13>C_2]acetate and [1-^<13>C]propionate. From the results of ^<13>C-NMR analysis of labeled compounds (2), it was revealed that the antibiotic contained nine intact acetate and six propionate units as shown in Fig. 2. The biosynthesis of okilactomycin (3), produced by a strain of Streptomyces sp., was also investigated by the feeding experiments of [1-^<13>C]- and [2-^<13>C]acetate, [1-^<13>C]propionate, [U-^<13>C_6]glucose, and L-[Me-^<13>C]methionine. The incorporation of seven intact acetate and four propionate units, a glycerol moiety from glucose, and a methyl group of methionine were observed by the ^<13>C-NMR analysis. The biosynthetic pathway may be unique as shown in Fig. 4 in light of the methyl of methionine incorporated into a methyl group of the antibiotic produced by an actinomycete.

著者

高橋 宣治 内田 健一 中川 彰 松崎 桂一 大村 智 中村 朝朗 三宅 洋子 武 佳和 甲斐荘 正恒

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.35, pp.762-768, 1993

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The biosynthesis of lactacystin, a new microbial metabolite which induces differentiation of neuroblastoma cells, was studied by ^<13>C NMR spectroscopy using various ^<13>C labeled precursors. The feeding experiment of L-[2-^<13>C ] leucine showed a strong enrichement at C-5 of Lactacystin. Incorporation of [1-^<13>C] isobutyrate labeled C-1, C-4, C-8, and C-14. These ^<13>C labeling patterns indicate that lactacystin consists of three biosynthetic units, namely isobutyrate (or L-valine), L-leucine, and L-cysteine. The C_<10> unit containing γ-lactam moiety arises by a condensation between methylmalonate semialdehyde and C-5 of the C_6 unit derived biosynthetically from L-leucine, followed by intramolecular cyclization. The stereochemistry of two diastereotopic methyl carbons of lactacystin which appeard at δc 19.85 and δc 21.37 was investigated by incorporation of a new type of chiral ^<13>C L-leucine (or L-valine), designated as the ^<13>C block labeled leucine (or valine), which was obtained from the fermentation of leucine producing organism using a mixture of 99% [U-^<13>C_6] glucose and natural glucose as a carbon source.

著者

大村 智 田中 晴雄 小山 泰昭 長井 敏明 丸茂 博大

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.20, pp.9-15, 1976

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In the course of our research for new antibiotics produced by actinomycetes, new antibiotics, nanaomycins A, B, C and D, effective against mycoplasma, fungi and Gram-positive bacteria were obtained from the cultured broth of a strain which had been isolated from a soil sample collected at Nanao-shi, Ishikawa prefecture and designated Streptomyces rosa var. notoensis. Evidence is put forward which describes the structure and stereochemistry of nanaomycins A, B, C and D, as I, V, IV and VI, respectively. In order to study biosynthesis and to determine the position of the hydroxyl group in the naphthoquinone moiety, a feeding experiment with [1-^<13>C] acetate was effectively carried out. Nanaomycins are synthesized from 8 acetate units via a "polyketide" in S. rosa var. notoensis. Since the carbon atom adjacent to the phenolic hydroxyl group was enriched with [1-^<13>C] acetate, the hydroxyl group is not at C-6 position but must be at C-9 position. The absolute configuration was determined by ORD comparisons. The results indicated that nanaomycin D is an enantiomer of kalafungin produced by S. tanashiensis. The production of each enantiomer by two different species belonging to the genus Streptomyces is of interest in the biosynthesis of a series of these antibiotics.