著者

野中 源一郎 松本 陽子 西岡 五夫

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.29, no.4, pp.1184-1187, 1981-04-25

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A novel hydrolyzable tannin named trapain has been isolated from Trapa japonica FLEROV. (Oenotheraceae), and the structure has been established as II on the basis of the spectroscopic and chemical evidences.

著者

梅澤 勲 野澤 雅子 南雲 紳史 秋田 弘幸

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.43, no.7, pp.1111-1118, 1995-07-15

被引用文献数

1

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Three kinds of oudemansin X, (-)-1,(+)-1 and (±)-1,were totally synthesized. The key point in the present chiral synthesis was the enantioselective acetylation of the racemic alcohols, (±)-5 and (±)-8,using lipase in an organic solvent. The synthetic (-)-1 was found to exhibit strong antifungal activity against several molds and yeasts.

著者

山下 純一 松本 宏 小林 和弘 野口 和春 安本 三治 上田 亨

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.37, no.9, pp.2287-2292, 1989-09-25

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A practical synthesis of 3'-O-benzyl-2'-deoxy-5-trifluoromethyluridine (1), a candidate antitumor agent for clinical testing, was developed from 2'-deoxy-5-iodouridine (3). Benzylation of 2'-deoxy-5-iodo-5'-O-trityluridine (14) with benzyl bromide and sodium hydride in tetrahydrofuran gave the 3'-O-derivative (16). Benzoylation of 16 afforded the N^3-benzoyl derivative (17). Coupling of 17 with trifluoromethylcopper, prepared from bromotrifluoromethane and copper powder in the presence of 4-dimethylaminopyridine, gave the 5-trifluoromethyl derivative (19) minimally contaminated with the 5-pentafluoroethyl compound. Deprotection of 19 furnished 1.

著者

寺田 忠史 山田 雄次 野村 誠 藤本 勝彦 野村 誠 山下 純一 / 小武内 尚 武田 節夫 南 慶典 吉田 健一郎 山口 秀夫

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.41, no.5, pp.907-912, 1993

被引用文献数

10

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1-&beta;-Alkyl derivatives of 1-desoxypodophyllotoxin were synthesized, and their cytotoxicity and inhibitory effects on DNA topoisomerase II (Topo-II) and tubulin polymerization were examined.The reaction of epipodophyllotoxin derivatives (1a-c) with trimethylallylsilane in the presence of boron trifluoride etherate gave 1-&beta;-allylated compounds (2a-c). The regiochemistry and the &beta;-stereochemistry of the 1-allyl group were confirmed by comparison of the <SUP>13</SUP>C-NMR spectra and NOE's (%) of 2c, podophyllotoxin (POD) and epipodophyllotoxin (1b). 1-&beta;-Alkyl-1-desoxypodophyllotoxin derivatives (3-8) were prepared from 2b.None of the tested compounds (3-8) showed any inhibitory effect on Topo-II. 1-&beta;-Propyl compound (3) and its 4'-demethyl compound (4) inhibited tubulin polymerization and the cytotoxicities of these compounds were equal to that of VP-16. 1-&beta;-(2, 3-Dihydroxypropyl) compounds (5 and 8) and 1-&beta;-(2, 3-diacetoxypropyl) compounds (6 and 7)showed no inhibitory effect on tubulin polymerization. Although 5 did not inhibit either Topo-II activity or tubulin polymerization, it showed a high cytotoxicity against sarcoma 180.

著者

寺田 忠史 藤本 勝彦 野村 誠 山下 純一 小武内 尚 武田 節夫 / 山田 雄次 山口 秀夫 山口 秀夫

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.40, no.10, pp.2720-2727, 1992

被引用文献数

27

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Various podophyllotoxin derivatives from desoxypodophyllotoxin (DPT) were synthesized to examine the structural relationships between the biological significance (cytotoxic effect, effects on DNA topoisomerase II and tubulin polymerization) in vitro and antitumor activity in vivo (L 1210).An intact 6, 7-methylenedioxy group of DPT is necessary to inhibit tubulin polymerization and topoisomerase II. 4'-Phenolic hydroxyl group of DPT is essential to inhibit DNA topoisomerase II and the inhibitory effect on DNA topoisomerase II contributes to a high cytotoxicity.The introduction of an aminoalkoxy group at 1-position of DPT enhances the inhibitory activity against DNA topoisomerase II and cytotoxic effect, causing the inhibitory activity against tubulin polymerization to disappear. The results of antitumor test in mice bearing L 1210 on podophyllotoxin derivatives suggest the following : 1) the strong cytotoxic effect itself is not a good indication of antitumor activity in vivo as long as it is associated with inhibition of tubulin polymerization. DNA topoisomerase II inhibitory effect contributes to an antitumor activity in vivo; 2) detailed measurements of cytotoxicity and inhibition on DNA topoisomerase II and tubulin polymerization in vitro are necessary to evaluate podophyllotoxin derivatives.

著者

野中 源一郎 原田 美沙子 西岡 五夫

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.28, no.2, pp.685-687, 1980-02-25

被引用文献数

2

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A new ellagitannin, eugeniin was isolated from cloves, the dried flower buds of Eugenia caryophyllata THUNB., and the structure was determined to be 1,2,3-trigalloyl 4,6-hexahydroxydiphenoyl β-D-glucopyranose.

著者

上田 修一 武田 節夫 山脇 一郎 山下 純一 安本 三治 橋本 貞夫

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.30, no.1, pp.125-131, 1982

被引用文献数

8

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A hydroxylated metabolite of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT), 1-(trans-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (trans-3'-OH-FT, VIII) and its isomer, 1-(cis-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (cis-3'-OH-FT, VI), were synthesized and isolated at high purity. As compounds related to FT metabolites, 2, 3'-anhydro-1-(cis-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (2, 3'-anhydro-FT, V), 1-(2, 5-dihydro-2-furanyl)-5-fluorouracil (3', 4'-dehydro-FT, XII) and 1-(5-acetoxytetrahydro-2-furanyl)-5-fluorouracil (5'-AcO-FT, XI) were also synthesized. The antitumor activities of these compounds against sarcoma 180 and L 1210 were examined. The activities of cis-3'-OH-FT (VI) and 2, 3'-anhydro-FT (V) were found to be lower than that of FT. The activity of 5'-AcO-FT (XI) was the same as that of FT. 3', 4'-Dehydro-FT (XII) showed much greater activity than FT.

著者

山下 純一 山脇 一郎 上田 修一 安本 三治 采見 憲男 橋本 貞夫

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.30, no.12, pp.4258-4267, 1982-12-25

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Six types of 5-fluorouracil (5-FU) derivatives were synthesized ; namely, 2,4-di-O-substituted, 2-O-substituted, 4-O-substituted, 1,3-disubstituted, 1-substituted and 3-substituted compounds. After oral administration of these compounds to rats, the blood levels of 5-FU were determined. Among O-substituted derivatives, a 4-O-substituted derivative was most easily activated to 5-FU and 2-O-substituted derivatives were next most easily activated. Among N-substituted derivatives, acyl and sulfonyl derivatives showed the highest 5-FU releasing abilities and 1-alkoxymethyl substituted derivatives showed low ability. N-Alkyl substituted derivatives were not activated to 5-FU. Several compounds which gave higher blood levels of 5-FU than that obtained with 1-(tetrahydro-2-furyl)-5-fluorouracil (Thf-FU), as well as same related compounds, were selected and their antitumor activities were examined. The 2-O-substituted derivatives, 2-butoxy-5-fluoro-4 (1H)-pyrimidone (11) and 2-benzyloxy-5-fluoro-4 (1H)-pyrimidone (19), were as effective as Thf-FU. The activities of 2,4-di-O-substituted derivatives, 2,4-dibutoxy-5-fluoropyrimidine (1) and 2,4-dibenzyloxy-5-fluoropyrimidine (6), against Ehrlich carcinoma and against sarcoma 180,respectively, were the same as those of Thf-FU. The 1-substituted derivatives, 1-ethoxymethyl-5-fluorouracil (49) and 1-(1-ethoxy-1-phenylmethyl)-5-fluorouracil (50), were found to be as effective as Thf-FU.

著者

山下 純一 安本 三治 橋本 貞夫

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.31, no.11, pp.3872-3877, 1983-11-25

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The mechanism of the condensation of 5-fluorouracil and 2-acetoxytetrahydrofuran (3), giving 1-(tetrahydro-2-furyl)-5-fluorouracil, was studied. An equilibrium between 2-acetoxytetrahydrofuran (3) and 2,3-dihydrofuran (4) was observed at 120-170℃ in dimethylformamide. It was found by the use of 1,3-dideuterio-5-fluorouracil that the condensation of 5-fluorouracil with 3 occurred both by direct substitution and by the formation of 4 from 3 followed by addition of the uracil to it. The contribution of the latter path increased with increase of the reaction temperature.

著者

山下 純一 武田 節夫 松本 宏 寺田 忠史 采見 憲男 安本 三治

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.35, no.5, pp.2090-2094, 1987-05-25

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Various O-acyl and N-acyl derivatives of 2'-deoxy-5-trifluoromethyluridine (F_3Thd) were synthesized; namely 5'-O-acyl, 3',5'-di-O-acyl, N^3-acyl, 3',5'-di-O-acetyl-N^3-acyl, 3',5'-di-O-carbamoyl and 3',5'-di-O-ethoxycarbonyl compounds. 5'-O-Acyl derivatives of 2'-deoxy-5-trifluoromethylcytidine were also synthesized. The antitumor activities of these compounds against sarcoma 180 were examined by oral administration to mice. Among the 5'- and 3',5'-diester compounds with aliphatic acids, the 5'-O-hexanoyl compound showed the highest activity. Full protection of the sugar moiety with aroyl or carbamoyl groups considerably decreased the activities, and those of the 3',5'-di-O-m-fluorobenzoyl and 3',5'-di-O-butylcarbamoyl compounds were the smallest. N^3-Benzoyl compounds were slightly more effective than F_3Thd but none of them showed higher activity than the effective O-acyl compounds. In the case of 5'-O-acylates of 2'-deoxy-5-trifluoroniethylcytidine, the 5'-O-benzoyl compound showed the highest activity.

著者

山脇 一郎 鈴木 雅博 小川 和男

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.42, no.4, pp.963-971, 1994-04-15

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Piperazinealkanol ester derivatives of indomethacin were prepared and tested for inhibitory activities against 5-lipoxygenase (5-LO) and cyclooxygenase (CO). They inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) formation by the cytosol of guinea pig polymorphonuclear leukocytes and thromboxane B_2 (TXB_2) formation by washed rabit platelet suspension. Of the test compounds, 2-[4-(2-hydroxyethyl)-1-piperazinyl]-1-phenylethyl 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetate dimaleate (II-8) was found to be the most active dual inhibitor of 5-LO and CO, and its inhibitory potency was higher than that of 2-[4-(3-hydroxypropyl)-1-piperazinyl]-ethyl [1-(4-chlorobenzoyl)-5-methoxy-2-methyl]-3-indolylacetate (CR-1015) (I), the lead compound.

著者

鈴木 雅博 田中 博道 宮坂 貞

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.35, no.10, pp.4056-4063, 1987-10-25

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Several 5-carbon-substituted 1-β-D-ribofuranosylimidazole-4-carboxamides were synthesized via the direct C-5 lithiation of a protected 4-carboxamide derivative as the key reaction step. Wittig reaction of a 5-formyl derivative was also examined.

著者

神田 博史 徳本 和佳子 坂本 季代恵 藤井 美智子 平井 裕子 山崎 和男 菰田 泰夫 中村 英雄 石原 茂正 内田 勝

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.33, no.4, pp.1367-1374, 1985-04-25

被引用文献数

12

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The MeOH extract of Ganoderma lucidum has an inhibitory action on histamine release from rat mast cells. From the physiologically active fraction of the extract, along with the known triterpenes ganoderic acids A and B, two new triterpenes were isolated and named ganoderic acids C and D. The structures of ganoderic acids C and D were determined to be 3β, 7β, 15α-trihydroxy-11,23-dioxo-5α-lanost-8-en-26-oic acid and 7β-hydroxy-3,11,15,23-tetraoxo-5α-lanost-8-en-26-oic acid respectively. Ganoderic acids C and D were shown to inhibit histamine release from rat mast cells. Quantitative analysis of these triterpenes was performed for the purpose of crude drug quality control.

著者

砂本 順三 岩本 清 上杉 辰顕 小島 一幸 古瀬 一磨

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.32, no.8, pp.2891-2897, 1984-08-25

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To evaluate the spermicidal effect of several nonionic surfactants against human spermatozoa, the physicochemical lysis of liposomal membranes by the surfactants has been investigated. Surfactants employed in this work were menfegol (TS-88), nonoxynol-9 (INP-90), octoxynol-9 (NOP-90), hexadecyltrimethylammonium bromide (CTAB), and sodium dodecylsulfate (SDS). Lysis of liposomes by these spermicidal surfactants was quantitatively followed by monitoring the induced release of carboxyfluorescein (CF) encapsulated in the interior of liposomes. When the liposomes reconstituted with boar spermatozoal lipids and about 31% (by wt.) cholesterol were employed, the sequence in efficiency of the surfactant-induced CF release from the liposomes was significantly correlated with that of efficiency of the surfactants in immobilizing human sperm (p<0.05). On the other hand, when egg lecithin liposomes or the liposomes reconstituted with boar spermatozoal lipids and cholesterol less than 21% (by wt.) were utilized, the sequence in efficiency of CF release from these liposomes coincided with that in the inhibiting effect of the surfactants on the fertilizing ability of sea urchin sperm. These effects were closely correlated with the membrane fluidity as controlled by the cholesterol content or lipid composition. Among menfegol analogues from TS-40 through TS-200,the efficiency in induced CF release from the liposomes showed a maximum at around ten ethylene oxide units length of the hydrophilic moiety in the surfactant. This was also the case for spermicidal effect of the TS-series surfactants. The data obtained are discussed at the molecular level from the viewpoint of the structural characteristics of the surfactants.

著者

Liu Weiping Qing Chen Chen Xizhu YE Qingsong YU Yao HOU Shuqian

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.56, no.5, pp.659-662, 2008-05-01

被引用文献数

1 6

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New JM118 (active form of satraplatin) analogues with N-cyclohexyl-1,3-propanediamine (N-chpda) as the carrier, cis-[Pt(N-chpda)X_2] (X_2=2Cl^- (1), oxalate (2), malonate (3), 1,1-cyclobutanedicarboxylate (CBDCA) (3), and 3-hydroxy-1,1-cyclobutanedicarboxylate(HO-CBDCA) (4)), have been synthesized and characterized by elemental analysis and spectroscopic data along with X-ray crystal structure for a representative compound cis-[Pt(N-chpda)Cl_2]. The complexes have also been evaluated for their in vitro anticancer activity. All these analytical data are in good agreement with the structures of the desired compounds. The Pt(II) is in a square planar environment and is coordinated by a chelating N-chpda ligand and 2Cl^- in cis position, and there are two crystallo-graphically independent cis-[Pt(N-chpda)Cl_2] molecules linked together by intermolecular N-H…Cl hydrogen bonds. Compounds 1 and 2 are very active against human lung cancer cell line (AGZY) and human lymphocytic leukemia cell line (Raji), and are much more active than carboplatin. Platinum(II) complexes with N-cyclohexyl-1,3-propanediamine is an alternative choice for mixed ammine/aminoplatinum anticancer drugs.

著者

松本 仁 磯部 明彦

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.29, no.3, pp.603-608, 1981-03-25

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The emission spectra and the fluorescence quantum yields of psoralens were measured in various solvents. We found that these compounds show a large Stokes shift, which can be explained in terms of intermolecular charge transfer interaction between a solute molecule and a solvent molecule in an excited singlet state. Psoralens have a larger fluorescence quantum yield in hydroxylic solvents than in non-hydroxylic solvents. These were in the following order : TMP&ap;5-MOP>PS&ap;8-MOP&ap;8-iso-AOP. We postulate that the fluorescence quantum yield is increased by the hydrogen bonding between a solute molecule and a solvent molecule in an excited singlet state. In addition, the fluorescence efficiency was enhanced by the presence of an electron-donating substituent group. The peak wavelengths of the phosphorescence spectra were little affected by the different solvents.

著者

阿部 フミ子 山内 辰郎

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.25, no.10, pp.2744-2748, 1977-10-25

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Cardenolides in the seeds, bark, and leaves of Cerbera manghas L. were investigated. From the seeds, tanghinigenin glycosides were isolated along with known digitoxigenin glycosides, cerberin, neriifolin, thevetin B, and 2'-O-acetyl thevetin B. From the barks of root and stem, gentiobiosyl thevetoside, glucosyl thevetoside, and thevetoside of tanghinigenin and 17βH-tanghinigenin were obtained. The cardenolides in the air-dried leaves were found to vary with seasons. 17βH-neriifolin is major and preferable to neriifolin in July, while 17βH-deacetyltanghinin and deacetyltanghinin present in the leaves of Feb.

著者

上野 明 福島 清吾 斉木 保久 原田 利一

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.12, no.3, pp.376-378, 1964-03-25

著者

大村 智 片桐 通子 小倉 治夫 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.16, no.7, pp.1181-1186, 1968

被引用文献数

1 11

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Leucomycin A<SUB>3</SUB> (I) was oxidized with active manganese dioxide to dehydroleucomycin A<SUB>3</SUB> (II) which was identical with magnamycin B. Acid treatment of I yielded demycarosylleucomycin A<SUB>3</SUB> (VII), which was converted to a triacetate showing mass spectrum M<SUP>+</SUP> (m/e 725), and this observation confirmed the structure of I. The diene system of I was assumed to have a trans-trans configuration on the basis of its NMR spectrum, and a full structure of I was proposed with stereochemistry.

著者

大村 智 中川 彰 山田 陽城 秦 藤樹 古崎 昭雄 渡辺 得之助

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.21, no.5, pp.931-940, 1973

被引用文献数

1 118

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A series of new antibiotics, Kinamycin A, B, C, and D which are mainly effective against gram-positive bacteria, were extracted with chloroform from the broth filtrate of Streptomyces murayamaensis sp. nov. HATA et OHTANI. Kinamycin C (I), C<SUB>24</SUB>H<SUB>20</SUB>O<SUB>10</SUB>N<SUB>2</SUB>, m/e 496 (M<SUP>+</SUP>), was determined to have an 8-hydroxynaphthoquinone skeleton, nitrile, acetoxyl, and tertiary methyl groups from its ultraviolet (UV), infrared (IR), and nuclear magnetic resonance (NMR) spectra, and was further found to have a unique structure of N-C-N from some chemical reactions and X-ray diffraction. Structure relationship among I and other components A, B, and D was assumed to be due to the difference in the number and position of the acetoxyl group from analyses of IR, NMR, and mass spectra of their acetylated compounds. The antimicrobial activity of the four kinamycins increases with the decreasing number of acetoxy group, in the order of kinamycin C, A, D, and B. In addition, some derivatives obtained during structural studies on I were found to have nearly equal or increased antimicrobia1 activity compared with I and kinamycin D (XI).