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Daisuke NOHARA, Masazumi WAKAMATSU, Masafumi GOTO, Tomoya SAKAI
1989 Volume 37 Issue 7 Pages
1685-1690
Published: July 25, 1989
Released on J-STAGE: March 31, 2008
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Kinetic and thermodynamic parameters were evaluated for the acylation and the deacylation steps in the hydrolysis of p-nitrophenyl acetate by α-chymotrypsin at pH 7.8 and at temperatures between 15 and 35°C by the use of stopped-flow and ordinary ultraviolet spectrophotometers. In contrast to the temperature dependencies of k
2 and K
s reported in the literature (P.A. Adams and E.R.Swart, Biochem.J., 161, 83(1977)), no kinetic anomaly was observed in either of the steps, but reasonable straight lines were obtained in both Arrhenius and van't Hoff plots. On the other hand, in the chymotryptic hydrolysis of N-benzoyl-L-alanine methyl ester a sharp kinetic anomaly was found. The discrepancy in the case of p-nitrophenyl acetate is discussed in connection with a possible conformational change of the enzyme, an alteration of the rate-limiting step or differences in the experimental procedures. The cause of the anomaly observed in the case of N-benzoyl-L-alanine methyl ester is also discussed in detail.
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Mitsuaki KODAMA, Kazuyoshi FUKUZUMI, Mitsushige KUMANO
1989 Volume 37 Issue 7 Pages
1691-1693
Published: July 25, 1989
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Cyclization of 13, 14-epoxygeranylgeranyl phenyl sulfide (2) was examined to determine whether 13- or 14-membered ring formation is preferred in the case of a disubstituted epoxide; the cis- and trans-epoxides were both found to cyclize to the 13-membered ring.
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Tsutomu SAKAKIBARA, Takashi KUME, Takahiro OHYABU, Tsunao HASE
1989 Volume 37 Issue 7 Pages
1694-1697
Published: July 25, 1989
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3, 5-Diphenylisoxazole and 2, 5-diphenyloxazole were regioselectively carbonylated under an atmosphere of carbon monoxide after the formation of arylpalladium(II) intermediates, to give bioactive o-benzoates substituted by isoxazole and oxazole rings in good yields.
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Kiyoshi HORITA, Yuji OIKAWA, Osamu YONEMITSU
1989 Volume 37 Issue 7 Pages
1698-1704
Published: July 25, 1989
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The required left (C1-C9) segment, (R)-2-[(2R, 5S, 6R)-6-[(R)-1-formylethyl]-5-methyltetrahydropyran-2-yl]butanoic acid, for a total synthesis of salinomycin was highly stereoselectively synthesized from D-glucose via a chelation-controlled Grignard reaction and a decarbonylation with Wilkinson's catalyst as important steps. The stereoselective synthesis of the middle (C10-C17) segment, (2R, 4S, 5S, 6R)-6-ethyl-2, 4-dimethyl-7-oxononan-5-olide, starting from D-glucose is also described.
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Kiyoshi HORITA, Satoshi NAGATO, Yuji OIKAWA, Osamu YONEMITSU
1989 Volume 37 Issue 7 Pages
1705-1716
Published: July 25, 1989
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(S)-4[(2R, 5R, 6S)-5-Ethyl-5-hydroxy-6-methyltetrahydropyran-2-yl]pentan-4-olide (5), an alkaline degradation product of salinomycin (1), was synthesized with complete stereoselectivity from D-mannitol and ethyl L-lactate.Compound 5 was then converted to (3R, 4S, 7S)-7-[(2R, 5R, 6S)]-5-ethyl-5-methoxymethoxy-6-methyltetrahydropyran-2-yl]-4, 7-bismethoxymethoxy-3-(tetrahydropyran-2-yloxy)oct-1-yne (3), a C18-C30 segment of 1, via Sharpless asymmetric epoxidation. Another C18-C30 segment, (R)-3-[2RS, 5S]-5-[(2R, 5R, 6S)-5-benzyloxy-5-ethyl-6-methyltetrahydropyran-2-yl]-2-methoxy-5-methyltetrahydrofuran-2-yl]-3-(4-methoxybenzyloxy)prop-1-yne (4), was synthesized more conveniently via coupling between a C19-C22 fragment prepared starting from D-glucose and a C23-C30 fragment prepared starting from D-mannitol and ethyl L-lactate.
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Kiyoshi HORITA, Yuji OIKAWA, Satoshi NAGATO, Osamu YONEMITSU
1989 Volume 37 Issue 7 Pages
1717-1725
Published: July 25, 1989
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The polyether antibiotic salinomycin was synthesized via coupling between the C10-C17 aldehyde, (2R, 4S, 5S, 6S, 7R)-6-ethyl-5, 7-isopropylidenedioxy-2, 4-dimethylnonanal, and C18-C30 acetylenes, for example, (3R, 4R, 7S)-4, 7-bis(tert-butyldimethylsilyloxy)-7-[(2R, 5R, 6S)-5-ethyl-5-(4-methoxybenzyloxy)-6-methyltetra-hydropyran-2-yl]-3-(4-methoxybenzyloxy)oct-1-yne, followed by the aldol condensation with the C1-C9 segment, (R)-2-[(2R, 5S, 6R)-6-[(R)-1-formylethyl]-5-methyltetrahydropyran-2-yl]butanoic acid. In this total synthesis, protection of hydroxy groups with the 4-methoxybenzyl group played an important role.
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Kiyoshi HORITA, Satoshi NAGATO, Yuji OIKAWA, Osamu YONEMITSU
1989 Volume 37 Issue 7 Pages
1726-1730
Published: July 25, 1989
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In order to confirm the structures of some key intermediates employed in the total synthesis of salinomycin (1), natural 1 was cleaved into C1-C9, C10-C30, C10-C17, C21-C30, and C19-C30 segments.
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Ken-ichi TANJI, Katsuhisa YAMAMOTO, Takeo HIGASHINO
1989 Volume 37 Issue 7 Pages
1731-1734
Published: July 25, 1989
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The nuclephilic substitution of 5-(methylsulfonyl)-3-phenyl-3H-1, 2, 3-triazolo[4, 5-d]pyrimidine (2) with potassium cyanide proceeded smoothly to give 3-phenyl-3H-1, 2, 3-triazolo[4, 5-d]pyrimidine-5-carbonitrile (6), but the same reaction did not take place in the case of 5-chloro-3-phenyl-3H-1, 2, 3-triazolo[4, 5-d]pyrimidine (1).Compounds 1 and 2 reacted with ethyl cyanoacetate in the presence of sodium hydride in tetrahydrofuran, giving ethyl α-cyano-3-phenyl-3H-1, 2, 3-triazolo[4, 5-d]pyrimidine-5-acetate (7). When acetote was used as a ketone, it added across the C
7, N
6-double bond, giving 7-acetonyl-5-chloro-6, 7-dihydro- (8a) and 7-acetonyl-6, 7-dihydro-5-(methylsulfonyl)-3-phenyl-3H-1, 2, 3-triazolo[4, 5-d]pyrimidines (8b), respectively, although the yields were low.The reaction of 1 with Grignard reagents resulted in the formation of addition products such as 7-alkylated 5-chloro-6, 7-dihydro-3-phenyl-3H-1, 2, 3-triazolo[4, 5-d]pyrimidines (9a-e). The substitution of the methylsulfonyl group of 2 with Grignard reagents proceeded to give the corresponding 5-alkylated 3-phenyl-3H-1, 2, 3-triazolo[4, 5-d]pyrimidines (11a-e).
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Makoto ISHIMATSU, Takashi TANAKA, Gen-ichiro NONAKA, Itsuo NISHIOKA, M ...
1989 Volume 37 Issue 7 Pages
1735-1743
Published: July 25, 1989
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Four novel dimeric and trimeric hydrolyzable tannins, nupharins C (1), D (13), E (15) and F (16), which possess a less favorable α-D-glucopyranose core with an atropisomeric (R)- or (S)-hexahydroxydiphenoyl group at the 3, 6-position, have been isolated from the rhizomes of Nuphar japonicum DC. (Nymphaeaceae). The structures of these compounds were established on the basis of spectroscopic and chemical evidence.
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Masaru KIHARA, Suwanna VANGVERAVONG, Kuniyoshi OHNISHI, Yasuhiro IMAKU ...
1989 Volume 37 Issue 7 Pages
1744-1747
Published: July 25, 1989
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10, 11-Diphenolic 8-hydroxy-5, 6, 7, 8-tetrahydrodibenz[c, e]azocine 3, having a partial structure of adrenaline, was prepared by demethylation of the dimethoxyazocine 12 with boron tribromide. The related monophenolic 8-hydroxyazocines 4 and 5 were prepared by cyclization of the dihalogeno-β-phenylethanolamines 6c and 7c with zerovalent nickel, followed by hydrolysis and debenzylation of the O-protected dibenz[c, e]azocines 13 and 14, respectively.
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Ryuichi ISOBE, Takashi TANAKA, Gen-ichiro NONAKA, Itsuo NISHIOKA
1989 Volume 37 Issue 7 Pages
1748-1750
Published: July 25, 1989
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Negative ion fast atom bombardment mass spectrometry employing a hexamethylphosphoric triamide-glycerol (1 : 1, v/v) mixture as a matrix has been found to facilitate the molecular weight determination of hydrolyzable tannins in their free forms, as well as the detection of diagnostic fragment ions.
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Takabumi NAGAI, Keizo OGAWA, Makoto MORITA, Mayumi KOYAMA, Akira ANDO, ...
1989 Volume 37 Issue 7 Pages
1751-1754
Published: July 25, 1989
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The ene reaction product of trifluoroacetone with cyclohexene, 3-(2, 2, 2-trifluoro-1-hydroxy-1-methylethyl)-cyclohexene (1), was converted to trifluorinated analogues of p- and m-menthane derivatives. For introduction of a functional group at suitable positions of the cyclohexene ring, oxidation of 1 was carried out to give 1-(2, 2, 2-trifluoro-1-hydroxy-1-methylethyl)-2-cyclohexen-1-ol (2), 4-(2, 2, 2-trifluoro-1-hydroxy-1-methylethyl)-2-cyclohexen-1-one (3) and 3-(2, 2, 2-trifluoro-1-hydroxy-1-methylethyl)-2-cyclohexen-1-one (4). Selenium dioxide gave only a small amount of 2. The best oxidizing reagent among those examined was tert-butyl hydroperoxide with chromium trioxide or chromium hexacarbonyl as a catalyst. In the presence of basic compounds such as pyridine or dimethylpyrazole, chromium trioxide gave a larger amount of 4 than 3, while in the presence of acetic acid, 3 was formed preferentially though the total yield was very low. Oxidation of 1 with tert-butyl hydroperoxide catalyzed by chromium hexacarbonyl gave 3 in excess over 4 in satisfactory yields. Treatment of the carbonyl compounds (3 or 4) with methylmagnesium iodide gave a p- or m-menthane skeleton with fluorine substituents, and these products were converted to some fluorine analogues of monoterpenes.
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Yoji IKUINA, Yoko KANZAWA, Yoshinori FUJIMOTO, Katsumi KAKINUMA
1989 Volume 37 Issue 7 Pages
1755-1757
Published: July 25, 1989
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(26-
13C)Desmosterol (1) and its 3-benzoate (8) and 3-tert-butyldimethylsilyl ether (9) were synthesized starting with (1-
13C)propionic acid and a steroidal C-24 aldehyde (2).
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Tozo FUJII, Taisuke ITAYA, Satoshi MATSUBARA
1989 Volume 37 Issue 7 Pages
1758-1763
Published: July 25, 1989
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The structures and absolute configurations of the cytokinins 1'-methylzeatin and its 9-riboside, both secreted by Pseudomonas syringae pv savastanoi, have been established as [R-(E)]-2-methyl-4-(9H-purin-6-ylamino)-2-penten-1-ol[(1'R)-2] and [R-(E)]-N-(4-hydroxy-1, 3-dimethyl-2-butenyl)adenosine [(1''R)-4], respectively, as a result of the chiral syntheses of (1'R)- and (1'S)-1'-methylzeatins [(1'R)-2 and (1'S)-2] and of their 9-β-D-ribofuranosides [(1''R)-4 and (1''S)-4] from D- and L-alanines. These zeatin derivatives were tested for cytokinin activity in the tobacco callus and the lettuce seed germination bioassays. The "natural" enantiomer (1'R)-2 was found to be as active as zeatin (1) itself and more active than its 9-riboside [(1''R)-4]. The "unnatural" enantiomer (1'S)-2 and its 9-riboside [(1''S)-4] were less active than the corresponding natural cytokinins, (1'R)-2 and (1''R)-4, respectively.
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Mamoru SUZUKI, Hiroshi MAEDA, Kazuhiko KONDO, Hiroshi SUGANO, Kazuo MA ...
1989 Volume 37 Issue 7 Pages
1764-1769
Published: July 25, 1989
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Various optically pure 3-substituted dihydroorotic acids (9, 12) were synthesized by the N-alkylation and Mitsunobu reaction of optically active benzyl or tert-butyl dihydroorotate (6, 10), followed by deprotection of the ester group.Moreover, optically pure 1-methyl (16, 17) and 1-ethyl (19) dihydroorotic acids were obtained by an optical resolution method.
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Toshihiro FUJIOKA, Masayo IWAMOTO, Yukiko IWASE, Shizuko HACHIYAMA, Hi ...
1989 Volume 37 Issue 7 Pages
1770-1775
Published: July 25, 1989
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Eight bayogenin glycosides, lobatosides A-H, were isolated from the herb of Actinostemma lobatum MAXIM.(Cucurbitaceae). The isolation of lobatosides A-H and the structures of lobatosides A, C, D and H are described.Lobatoside A is 3-O-[α-L-arabinopyranosyl-(1→2)-β-D-glucopyranosyl]bayogenin (2β, 3β, 23-trihydroxyolean-12-en-28-oic acid). Lobatosides C, D and H are dicrotalic acid (3-hydroxy-3-methylglutaric acid) esters of the 28-[α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl] ester, 28-[β-D-glucopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl] ester and 28-[β-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl] ester of lobatoside A, respectively. Dicrotalic acid is linked at one end to the C
4-hydroxyl group of the α-L-arabinopyranosyl group in the C
3-linked sugar moiety, and at the other end to the C
4-hydroxyl group of the α-L-rhamnopyranosyl group in the ester-linked sugar moiety to form a macrocyclic structure ("cyclic bisdesmoside"). Lobatoside H was proved to be identical with tubeimoside I isolated from the tuber of Bolbostemma paniculatum (MAXIM.) FRANQUET (Cucurbitaceae).
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Kazuhisa FUNAKOSHI, Nagako TOGO, Yukari TAURA, Kiyoshi SAKAI
1989 Volume 37 Issue 7 Pages
1776-1779
Published: July 25, 1989
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In Rh(I) (Wilkinson)-catalyzed cyclization of 6-octen-1-als, the formation of cis-cyclohexanols is in contrast to Lewis acid-catalyzed cyclization, which affords predominantly the trans-cyclohexanols. However, 6-octen-1-als with a cyclic acetal (1, 3-dioxane or 1, 3-dioxolane) at the C
3-position were stereoselectively cyclized to only the trans-products.The aldehyde with a chiral protecting group ((4R, 6R)-dimethyl-1, 3-dioxane with the C
2-axis) at the C
3-position was diastereoselectively cyclized to the trans-cyclohexanol, and on a basis of the absolute stereochemistry of the cyclized product, the cyclization mechanism is tentatively proposed. The effect of 4R-methyl-1, 3-dioxane at the C
3-position was also examined.
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Kohji OZEKI, Teru ICHIKAWA, Hiroyuki TAKEHARA, Kenjiro TANIMURA, Makot ...
1989 Volume 37 Issue 7 Pages
1780-1787
Published: July 25, 1989
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A series of 2-anilino-1, 6-dihydro-6-oxo-5-pyrimidinecarboxylic acids with various substituents was synthesized and evaluated in the rat passive cutaneous anaphylaxis test for antiallergic activity. High activity by intraperitoneal and oral administrations was observed for the 3-trifluoromethyl and 2-alkoxyanilino derivatives (64, 79, 81, 82 and 85).Structure-activity relationships are discussed.
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Hiroshi MASUMOTO, Kaoru TAKEUCHI, Shigeru OHTA, Masaaki HIROBE
1989 Volume 37 Issue 7 Pages
1788-1794
Published: July 25, 1989
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Cytochrome P450 model and liver microsomal oxidations of drugs were compared using phencyclidine. In general, the chemical reaction systems produced many oxidation products. Besides the formation of the cyclohexane-4-hydroxyl compound (2), hydroxylation of the aromatic ring was favored in the Fenton reaction system (Fe
2++H
2O
2). Formation of an m-hydroxylated product (m-5) was the main aromatic oxidation pathway in the Udenfriend reaction (Fe
2+-ascorbic acid-O
2), and 2, the piperidine-3-hydroxyl compound (3), and the piperidine-4-hydroxyl compound (4) were also formed. In the system using meso-tetraphenylporphinatoiron chloride (Fe(III)TPPC1) with an oxidant, the main product was the piperidine-3-oxo compound (8). In the liver microsomes system, 2, 4, 8, and m-5, which were all generated by the chemical oxidation reactions, were detected as metabolites of phencyclidine. They were formed by cytochrome P450-dependent reactions. Chemical oxidation systems can be used to study drug metabolism; they can reveal some tendencies of the real metabolis reactions, are easy to operate, and yield sufficient amounts of product.
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Morihiro MITSUKUCHI, Tomoyuki IKEMOTO, Minoru TAGUCHI, Shohei HIGUCHI, ...
1989 Volume 37 Issue 7 Pages
1795-1801
Published: July 25, 1989
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As part of the search for new topical antiinflammatory agents, various 21-substituted corticosteroids having sulfur-containing moieties were prepared and tested for vasoconstrictive activity in humans. A structure-activity relationship study revealed that substitution of the 21-hydroxy group with a lower alkyl-thio group enhanced the activity. The activities of the 21-methylthio (3Ad) and the 21-ethylthio (3Ae) compounds were more potent than that of 9α-fluoro-11β, 21-dihydroxy-16β-methyl-17α-valeroyloxy-1, 4-pregnadiene-3, 20-dione (betamethasone 17-valerate, BV).
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Shoji YAHARA, Michiko OHTSUKA(nee IKESA), Kimiko NAKANO, Toshihiro NOH ...
1989 Volume 37 Issue 7 Pages
1802-1804
Published: July 25, 1989
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A new glucuronide, (22R)-3β, 16β, 22, 26-tetrahydroxycholest-5-ene 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-gluc-uronopyranoside (1), was isolated from the aerial parts of Chinese Solanum lyratum THUNB. The structure of this new steroidal glucuronide was deduced by spectroscopic means and the identity of its aglycone was substantiated by comparison with an authentic sample derived from diosgenin acetate.
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Taichi OHMOTO, Kazuo KOIKE, Hiroshi FUKUDA, Katsuyoshi MITSUNAGA, Keng ...
1989 Volume 37 Issue 7 Pages
1805-1807
Published: July 25, 1989
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A new nor-diterpene lactone, picrodendrin A, was isolated from the bark of Indonesian Picrodendron baccatum(Simaroubaceae), and its structure was established on the basis of spectroscopic data and an X-ray crystal structure analysis.
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Feng-E Wu, Kazuo KOIKE, Tamotsu NIKAIDO, Yohko SAKAMOTO, Taichi OHMOTO ...
1989 Volume 37 Issue 7 Pages
1808-1809
Published: July 25, 1989
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Six β-carboline alkaloids were isolated from a Chinese medicinal plant, Arenaria kansuensis. The structures of four new alkaloids named arenarines A, B, C, and D were identified based on spectral and chemical evidence.
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Katsuhiko ONO, Hideo NAKANE, Zeng-Mu MENG, Youki OSE, Yoshimichi SAKAI ...
1989 Volume 37 Issue 7 Pages
1810-1812
Published: July 25, 1989
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Forty preparations of the extracts from 28 kinds of Asian herbs were tested for ability to inhibit the activities of murine retroviral reverse transcriptase and human deoxyribonucleic acid (DNA) polymerases. Among the 40 extracts, 35 inhibited reverse transcriptase activity and 29 inhibited DNA polymerase α activity. The inhibitory potencies of these extracts were expressed as the 50% inhibition concentrations (IC
50), at which the enzyme activities were inhibited by 50%. Very strong inhibitions were observed with the extracts from Millettia pachycarpa (Leguminosae) and Mallotus apelta (Euphorbiaceae) as shown by their low IC
50 values for reverse transcriptase (0.4-0.5 μg/ml) and DNA polymerase α(0.9-1.4 μg/ml). Enzyme kinetic analysis revealed that the mode of inhibition of reverse transcriptase by these two extracts was competitive with respect to the template·primer [poly(rA)·oligo(dT)] and noncompetitive with respect to deoxythymidine triphosphate (dTTP) substrate. Besides reverse transcriptase and DNA polymerase α, DNA polymerase I and ribonucleic acid (RNA) polymerase from E. coli were inhibited by these two extracts. These results indicate that the herb extracts contain as yet unidentified substance(s) which inhibit the activities of reverse transcriptase and cellular DNA polymerases.
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Munekazu IINUMA, Toshiyuki TANAKA, Mizuo MIZUNO, Tomoyuki KATSUZAKI, H ...
1989 Volume 37 Issue 7 Pages
1813-1815
Published: July 25, 1989
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To clarify the structure-activity correlation of flavonoids for inhibition of aldose reductase, about fifty flavonoid compounds were screened. The presence of hydrophobic substituents on the A ring and hydrophilic substituents on the B ring of the flavonoid skeleton was suggested to improve the potency of inhibitory activity. The activities of extracts of Scutellaria baicalensis, Andrographis paniculata and Gutierrezia microcephala are also described.
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Kayoko MIURA, Takashi INAGAKI, Nobuji NAKATANI
1989 Volume 37 Issue 7 Pages
1816-1819
Published: July 25, 1989
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Two new biphenyls, 3, 4, 3', 4'-tetrahydroxy-5, 5'-diisopropyl-2, 2'-dimethylbiphenyl (4a) and 3, 4, 4'-trihydroxy-5, 5'-diisopropyl-2, 2'-dimethylbiphenyl (5), were isolated from the leaves of thyme (Thymus vulgaris L.). Their structures were elucidated by spectroscopic methods and chemical transformations. Both biphenyls 4a and 5 showed more effective deodorant activity against methyl mercaptan than did rosmanol, carnosol or sodium copper chlorophylline.
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Johji YAMAHARA, Toshimasa YAMADA, Tetsuya KITANI, Yoshikazu NAITOH, Ha ...
1989 Volume 37 Issue 7 Pages
1820-1822
Published: July 25, 1989
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In order to develop new drugs from natural products, constituents of natural medicines were examined for their effectiveness in the KCN-induced anoxia model in mice. Methanol extract from a Chinese medicine, evodia (fruits of Evodia rutaecarpa BENTH. or E. officinalis DODE), had a significant effect in the KCN-induced anoxia model in mice and therefore the active constituents were further examined. The results indicated that the antianoxic action of evodia was found in the fraction containing evodiamine. Further analysis of the active constituent indicated that evodiamine and rutaecarpine, indole-alkaloids found in large amounts in the Chinese medicine evodia, were mainly responsible for the antianoxic action.
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Tomohiko YOSHIDA, Hirokazu TANIGUCHI, Shuji OTUKA, Sabro NAKANO
1989 Volume 37 Issue 7 Pages
1823-1826
Published: July 25, 1989
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A fluorometric method for the determination of 1-naphthol (NP) with 3-amino-2(1H)-quinolinethione (AQT) was developed. The method is based on the oxidation of NP by Fremy's salt and the reaction with AQT in an acid medium, followed by extraction of a red fluorescent product (excitation maxima, 535 and 575 nm; emission maximum, 600 nm) with carbon tetrachloride after making the reaction mixture strongly basic. The calibration curve was linear in the range from 0.01 to 1.2 μg/ml of NP. This method was applied for the fluorometric determination of Carbaryl (NAC, 1-naphthyl N-methylcarbamate)(0.01-1.8 μg/ml), which was hydrolyzed with potassium hydroxide and determined by the same method as NP. The coefficient of variation was 13% (n=10) or 1.5% (n=10) for 0.3 μg/ml of NP or NAC, respectively.
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Itsuo MORI, Yoshikazu FUJITA, Kinuko IKUTA, Shoko KITANO, Hiroshi KAWA ...
1989 Volume 37 Issue 7 Pages
1827-1830
Published: July 25, 1989
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The fluorescence quenching reaction between fluorescein mercury or halogeno-fluorescein mercury compounds (fl.Hg, 2, 7- or 2, 4-dichloro-fl.Hg, 3', 4', 5', 6'-tetrachloro-fl.Hg, mercurochrome) and β-lactam antibiotics (ampicillin (AB-PC) and cephalexin (CEX)) was investigated, and mercurochrome was selected for the detection of β-lactam antibiotics;the detection limit was about 0.8 μg/ml.A fluorimetric assay of β-lactam antibiotics was established by measuring the fluorescence of mercurochrome and mercurochrome-β-lactam antibiotics solutions in weakly basic media to determine the degree of fluorescence quenching.The maximum emission wavelength of mercurochrome solution was at 544 nm with excitation at 470 nm. The calibration graphs were linear over the ranges of about 0-6 μg/ml β-lactam antibiotics penicillins (AB-PC, penicillin G, sulbenicillin, amoxicillin, cyclacillin, oxacillin, hetacillin and piperacillin) and cepham antibiotics (CEX, cefazolin, cephaloglycin, cephaloridine and cefpyramide), and the relative standard deviation was 2.7% for 1.4 μg/ml of AB-PC(n=5).This fluorescence quenching reaction between mercurochrome and β-lactam antibiotics was applied in a survey of decomposition and remaining potency of β-lactam antibiotics.
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Hidetoshi ARAKAWA, Masako MAEDA, Akio TSUJI, Toyozoh TAKAHASHI
1989 Volume 37 Issue 7 Pages
1831-1833
Published: July 25, 1989
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A simple chemical method for introducing biotin into nucleic acids has been developed for the synthesis of non-isotopic hybridization probes. The method is based on the reaction of biotin hydrazide with amino residues of nucleic acids by using glutaraldehyde as a bifunctional coupling reagent.Biotin-labelled deoxyribonucleic acid (DNA) was detected by the use of alkaline phosphatase-labelled avidin, and alkaline phosphatase activity was measured by colorimetric and chemiluminescence methods. The chemiluminescence method using the nicotinamide adenine dinucleotide phosphate (NADP)/alcohol/alcohol dehydrogenase/microperoxidase/isoluminol system gave the highest sensitivity. A few picograms of λ-phage DNA coated on a microtiter plate well could be detected by this method.
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Hiroshi HOSODA, Reiko TSUKAMOTO, Toshio NAMBARA
1989 Volume 37 Issue 7 Pages
1834-1837
Published: July 25, 1989
Released on J-STAGE: March 31, 2008
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The sensitivities of monoclonal antibody-based enzyme immunoassays for 11-deoxycortisol using alkaline phosphatase (AP), horseradish peroxidase (HRP), β-galactosidase (β-GAL) and glucose oxidase (GOD) as labels were compared. The anti-11-deoxycortisol antibody used was that produced in ascites by inoculating antibody-secreting hybridoma cells into mice. Enzyme labeling of 11-deoxycortisol was carried out by the N-succinimidyl ester method. The activated ester of 4-(2-carboxyethylthio)-11-deoxycortisol was treated with each enzyme to give a homologous enzyme-labeled antigen. In the competitive immunoassay, the bound and free enzyme-labeled antigens were separated by a double antibody method and the enzymic activity of the immune precipitate was determined by colorimetric and fluorimetric methods. The AP activity was measured in three ways using p-nitrophenyl phosphate, nicotinamide adenine dinucleotide phosphate (NADP), and 4-methylumbelliferyl phosphate as substrates. o-Nitrophenyl β-D-galactopyranoside and 4-methylumbelliferyl β-D-galactopyranoside were used for β-GAL, and 3, 3', 5, 5'-tetramethylbenzidine (TMB) and 3-(p-hydroxyphenyl)propionic acid (HPPA) for HRP. In the case of GOD, TMB and HPPA were used in combination with HRP. A dose-response curve with a high sensitivity was obtained in each 11-deoxycortisol assay system by the use of a minimum amount of the enzyme-labeled antigen at an appropriate dilution of monoclonal anti-11-deoxycortisol antibody (K
a=2×10
10M
-1). The amounts of 11-deoxycortisol needed to displace 50% of the bound label ranged from 5 to 15 pg in the colorimetric methods, and 4-9 pg in the fluorimetric methods. It was found that the assay using the HRP label was the most sensitive, and the AP, GOD and β-GAL labels gave nearly equal sensitivities. An interesting finding was obtained on the so-called bridging phenomenon, which is a factor influencing the sensitivity of hapten enzyme immunoassays.
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Yoshiyuki ADACHI, Naohito OHNO, Masumi OHSAWA, Kichiro(deceased) SATO, ...
1989 Volume 37 Issue 7 Pages
1838-1843
Published: July 25, 1989
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Antitumor glucan, grifolan LE (GRN LE), from Grifola frondosa was chemically modified to examine the structure-function relationship of the products. Modification by periodate, borohydride and acid hydrolysis of side chains of GRN LE did not alter properties such as helical conformation and antitumor activity of GRN LE. Introduction of carboxylic acid groups into the side chains by oxidation with periodate and with sodium chlorite (GRN LE-PC), and substitution with carboxymethyl (CM) or hydroxyethyl (HE) groups abolished the gel-forming ability of GRN LE.Significant antitumor activity was observed in all of the derivtives having gel-forming ability as well as some derivatives having no such ability. These results suggested that essential factors required for antitumor activity were (1→3)-β-D-glucosy linkages and high molecular weight, and that accessory groups could be linked to the main chain without loss of antitumor activity in a higher ratio than that of gel-forming ability.
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Hiromi HAYASHI, Koji UENO, Takamitsu HORI, Yukio NAITO, Teruhiko SHIMO ...
1989 Volume 37 Issue 7 Pages
1844-1848
Published: July 25, 1989
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A high cholesterol/cholate diet induced hypercholesterolemia and fatty liver in both spontaneously hypertensive rats(SHR) and normotensive control rats (WKY). However, in contrast to previous concepts, the levels of cholesterol ester, triacylglycerol and phosphatidylcholine in plasma as well as triacylglycerol in liver were higher in WKY than in SHR fed a normal diet. The high cholesterol/cholate diet elevated the levels of plasma cholesterol, plasma cholesterol ester and hepatic triacylglycerol, and the extent of elevation was significantly higher in WKY than in SHR. Increases both in monoene/saturated ratios, an indication of elevated Δ
9-desaturase activity, and in linoleate/arachidonate ratios, a possible indication of impaired desaturation-elongation activity, were observed in hepatic and plasma lipids of both strains fed the high cholesterol/cholate diet. The increases in monoene/saturated ratios were similar in both strains, but the increases in the linoleate/arachidonate ratios were higher for the plasma cholesterol esters of WKY than of SHR.The n-6/n-3 ratios of plasma and hepatic lipids were higher in WKY than in SHR throughout the experiments. These diet-induced changes observed in hepatic and plasma lipids were not reflected in the aortic lipids.Thus, hypertension per se does not promote the development of hyperlipemia and fatty liver induced by a high cholestrol/cholate diet. Our results also suggest that the metabolism of polyenoic fatty acids is different between SHR and WKY.
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Toshiharu MATSUO, Keijiro UCHINO, Toshikatsu TOUKAIRIN, Masaya IWAMOTO ...
1989 Volume 37 Issue 7 Pages
1849-1851
Published: July 25, 1989
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New 5'-nucleotidase-inhibitory polyphenols named NPF-86IA, NPF-86IB, NPF-86IIA and NPF-86IIB were isolated from the seeds of Areca catechu L. The ability of the inhibitors to precipitate gelatin was investigated by microturbidimetry. These inhibitors produced weak turbidity. As 5'-nucleotidase is a kind of phosphatase, we examined the effects of these inhibitors on alkaline and acidic phosphatases. While they showed moderate inhibitory effects on the activity of acidic phosphatases, they did not have any significant effect on the activity of alkaline phosphatase. Therefore, they showed a higher inhibitory effect on the 5'-nucleotidase than the other phosphatases. Murine macrophages were directly stimulated by the 5'-nucleotidase inhibitors.
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Michiko YOSHII, Mizuho UNE, Kenji KIHIRA, Taiju KURAMOTO, Takahiko HOS ...
1989 Volume 37 Issue 7 Pages
1852-1854
Published: July 25, 1989
Released on J-STAGE: March 31, 2008
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In order to confirm the structure of α-trichechol, the major bile alcohol of the West Indian manatee, chemical synthesis of 5β-cholestane-3α, 6β, 7α, 25, 26-pentol was carried out. The chain of 3α-hydroxy-5β-chol-6-en-24-oic acid was elongated by an Arndt-Eistert reaction to form 3α-hydroxy-26, 27-dinor-5β-cholest-6-en-25-oic acid. The unsaturated C
25 bile acid was converted into 3α, 6β, 7α-trihydroxy-25-homo-5β-cholan-25-oic acid by 1, 2-glycol formation of the Δ
6-double bond. The acetylated derivative of the trihydroxy C
25 bile acid was then converted into 3α, 6β, 7α, 26-tetraacetoxy-27-nor-5β-cholestan-25-one by successive treatment with thionyl chloride, diazomethane, and acetic acid. A Grignard reaction of the 25-oxo compound with methylmagnesium iodide afforded the desired bile alcohol, 5β-cholestane-3α, 6β, 7α, 25, 26-pentol. By direct comparison with the synthetic pentahydroxy bile alcohol, the structure of the naturally occurring α-trichechol was determined to be 5β-cholestane-3α, 6β, 7α, 25, 26-pentol.
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Shizuo NAKAJIN, Kazuaki TAKAHASHI, Masato SHINODA
1989 Volume 37 Issue 7 Pages
1855-1858
Published: July 25, 1989
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The inhibitory effect of an anabolic steroid, stanozolol, on testicular microsomal cytochrome P-450 (17α-hydroxylase/C
17, 20-lyase)(P-450
17α/lyase) and the nature of the interaction were compared with those of other anabolic steroids, furazabol and mestanolone. Stanozolol markedly inhibited Δ
16-C
19-steroid synthesizing activity, 17α-hydroxylase and C
17, 20-lyase activities, which were mediated by oxygenase activities of testicular microsomal cytochrome P-450
17α/lyase. In addition, stanozolol was a competitive inhibitor of 17α-hydroxylase (K
i=6.31 μM) and C
17, 20-lyase (K
i=1.30 μM) activities in the reconstituted enzyme system.The interaction of cytochrome P-450
17α/lyase with stanozolol induced a type I difference spectrum (peak at 387 nm and trough at 418 nm) with a dissociation constant (K
s) of 1.47 μM.
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Makoto NAKAGAWA, Kimie FUKUYAMA, William L. EPSTEIN, Akira HARA, Hideo ...
1989 Volume 37 Issue 7 Pages
1859-1863
Published: July 25, 1989
Released on J-STAGE: March 31, 2008
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Plasminogen activator (PA) and PA inhibitor were partially purified from 2-d-old rat epidermis and characterized in order to elucidate the enzyme-inhibitor interaction in epidermis. PA extracted with buffer containing KSCN was first purified by Blue-Sepharose affinity chromatography. Separation of two PAs, with relative molecular mass (M
r) of 66000 and 44000, was accomplished by Con A-Sepharose column chromatography. The M
r 66000 enzyme had the properties of tissue-type PA (t-PA), while the M
r 44000 enzyme showed those of urokinase-type PA (u-PA) as determined by immunological and fibrin-binding studies. PA inhibitor was extracted in 1, 4-piperazinediethanesulphonic acid buffer and purified by (NH
4)
2SO
4 precipitation, gel filtration followed by a Mono Q column in an FPLC system. This inhibitor showed M
r 60000 and inhibited human u-PA activity in a dose- and time-dependent manner, but did not inhibit the activity of t-PA from human and murine melanoma cells or plasmin. It inhibited epidermal PA, M
r 44000, more effectively than it did the M
r 66000 epidermal PA. It was stable at 60°C for 60 min or between pH 5 and 11. This study indicates that both u-PA and t-PA function in normal rat epidermis. On the other hand, an inhibitor which preferentially acts against u-PA exists, but inhibitor to t-PA does not appear to operate under normal epidermal functions.
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Akira KOSHIRO, Toshio FUJITA, Yukiko HARIMA, Kunihiko FUKAI, Fumio YON ...
1989 Volume 37 Issue 7 Pages
1864-1869
Published: July 25, 1989
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The kinetics of the degradation and tautomerization of cefotetan in aqueous solution was studied at 25°C and ionic strength 0.6 over the pH range of 2.0-12.0. The degradation rates of cefotetan and its tautomer were found to be identical and the rate law reflected the spontaneous hydrolysis of each molecular species and the hydroxide ion-catalyzed hydrolysis of the dianionic species. The tautomerization was remarkable especially in the alkaline region and the equilibrium of the tautomerization shifted toward the tautomer as the hydroxide ion concentration was increased.Divalent metal ions were found to catalyze the tautomerization by chelation. Electron transfer triggered by the attack of hydroxide ion at the amide of the 1, 3-dithiethane moiety and electron withdrawal by hydronium ion from the nitrogen atom on the isothiazole ring of the anion intermediate formed from the tautomer by hydroxide ion were proposed as the mechanisms of the forward and reverse tautomerizations, respectively. The latter reaction is considered to be accompanied with epimerization. The apparent activation energies of the degradation at pH 3.0, 7.0 and 9.0 and those of the forward and reverse tautomerizations at pH 9.0 were 23.3, 22.9, 31.4, 35.5 and 24.4 kcal mol
-1, respectively.
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Hirohiko INADA, Makiko ENDOH, Kazunori KATAYAMA, Masawo KAKEMI, Tamots ...
1989 Volume 37 Issue 7 Pages
1870-1873
Published: July 25, 1989
Released on J-STAGE: March 31, 2008
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Permeation of sulfisoxazole (SIX) across the excised rat skin were studied using two chamber cell with four electrodes, under three successive experimental conditions : without current for 3 h (treatment I), with current for 4 h (treatment II) and without current for 3 h (treatment III). Transport of SIX was significantly increased by iontophoresis. The enhancement ratio of SIX flux were reasonably predicted by Coldman's equation. There was no significant difference (p<0.05) between the flux in treatent I and treatment III. On the basis of the flux reversibility, it was concluded that skin alteration did not occur when the applied electric potential was below 5.025 V. Although a prominent current-induced volume flow (from the anodal side to the cathodal side) was observed during current exposure, SIX flux was not influenced by the volume flow. The flux enhancement of SIX was mainly dependent on transdermal potential difference.
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Yoshiharu KARUBE, Koji IWAMOTO, Junko MIURA, Jiro TAKATA, Yoshikazu MA ...
1989 Volume 37 Issue 7 Pages
1874-1876
Published: July 25, 1989
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The
99mTc and
57Co complexes of ethylenediamine-N, N-diacetic acid (EDDA) are accumulated in tumor tissue. The complexes and related radioactive compounds were administered to experimental animals bearing Ehrlich tumor, and the blood, tumor, abscess, and other tissues were separated, fractionated and analyzed. In blood, the EDDA complexes of
99mTc and
57Co were in dialyzable forms, whereas other tumor-nonlocalizing compounds were in undialyzable or protein-bound forms. The tumor/blood and tumor/muscle ratios of the radioactivity showed that the complexes had the high affinity for tumor tissues. Density gradient centrifugation analysis of the ascites tumor tissues showed that a significant amount of the radioactivity of the complexes was present in tumor cells. Subcellular fractionation of solid tumor tissue showed that the radioactivity was present in nuclear fraction.
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Nobuhito SHIBATA, Tokuzo MINOUCHI, Yukio HAYASHI, Hidehiko SHIBATA, Ta ...
1989 Volume 37 Issue 7 Pages
1877-1880
Published: July 25, 1989
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The effects of temperature, hematocrit (Hct), lipid level in plasma and cyclosporin A (CyA) level in whole blood on the concentration of CyA in plasma measured by high-performance liquid chromatography were studied in vitro. With rise in blood storage temperature before cells were removed, the concentration of CyA in plasma was increased in the temperature range between 10°C and 37°C, but was decreased between 4°C and 10°C. With rise in Hct, the concentration of CyA in plasma was decreased, and it was more markedly decreased at the blood storage temperature of 4°C than at 37°C. A lipid supplementation study showed that the concentration of CyA in plasma was increased with rise in plasma triglyceride level and in plasma cholesterol level at the storage temperature of 4°C but not at 37°C. Studies of the effect of CyA concentration in blood on the CyA distribution in blood demonstrated that the cellular/plasma concentration (C/P) ratio at low levels (<200 μg/ml) of plasma CyA ranged from 4 to 10 and was about 2 times higher than that at higher concentrations at 4°C, but the ratio was relatively constant at 37°C. The saturation capacity of the cellular fraction for CyA showed considerable individual variation, but there was no difference between the capacities at 4°C and 37°C. The separation of plasma after equilibration at 37°C made it possible to avoid the variations in the distribution of CyA in whole blood associated with changes in Hct, lipid level in plasma and CyA level in whole blood, and to obtain a measurement reflecting the physiologically significant concentration of CyA in plasma.
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Toshio OGUCHI, Katsuhide TERADA, Keiji YAMAMOTO, Yoshinobu NAKAI
1989 Volume 37 Issue 7 Pages
1881-1885
Published: July 25, 1989
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Aqueous methyl p-hydroxybenzoate (MPHB) solutions containing various amounts of α-cyclodextrin (α-CD) were freeze-dried. The crystalline states of MPHB and the freeze-dried products have been investigated. From a comparison of the powder X-ray diffraction patterns, it was found that rapid freezing provided amorphous products, while slow freezing provided crystalline inclusion complexes. To estimate the amorphous MPHB fraction, crystalline MPHB was removed by means of sublimation treatment, and residual MPHB was determined by ultraviolet spectrophotometry. It was found that the amount of amorphous MPHB in a rapidly frozen sample was greater than that in a slowly frozen sample.Amorphous MPHB molecules were considered to exist in two different states, namely the included state in the α-CD cavity and the dispersed state in the intermolecular hydrogen-bonding network of α-CDs. From studies with linear oligosaccharides, it was suggested that the freezing condition influenced the amount of MPHB molecules dispersed in the intermolecular hydrogen-bonding network.
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Toshio OGUCHI, Katsuhide TERADA, Keiji YAMAMOTO, Yoshinobu NAKAI
1989 Volume 37 Issue 7 Pages
1886-1888
Published: July 25, 1989
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The molecular interaction in a ground mixture of α-cyclodextrin (α-CD) and methyl p-hydroxybenzoate (MPHB) has been studied as a function of the mixing molar ratio. The states of MPHB molecules were investigated by means by powder X-ray diffraction, differential scanning calorimetry measurement and the determination of remaining MPHB after sublimation. The results indicated that in the ground mixture the MPHB molecules could exist in a mono-molecular dispersed state in the hydrogen bonding network of α-CD as well as in the α-CD cavity. It was suggested that two types of crystalline MPHB, fine crystals embedded in the α-CD matrix and intact crystals, were also present in the ground mixture of molar ratio 5 (MPHB/α-CD) or above.
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Hisakazu SUNADA, Itaru SHINOHARA, Akinobu OTSUKA, Yorinobu YONEZAWA
1989 Volume 37 Issue 7 Pages
1889-1894
Published: July 25, 1989
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The dissolution of n-propyl p-hydroxybenzoate was conducted under the sink condition, and was simulated from the changes of surface area during the dissolution process and by means of the cube root law. The surface area of the samples was estimated by using a LUZEX image analyzer. The two simulation methods gave almost the same dissolution rate constants.Dissolution of systems prepared by mixing sieved samples at various weight ratios was also carried out, and these dissolution processes were simulated by means of the cube root law. The apparent mean diameter of the mixed systems was well estimated in terms of particle size and weight ratio of the components. Hence, the mixed systems were converted into several imaginary equivalent systems, and the applicability of the cube root law and the validity of the estimation of apparent mean diameter of the mixed system were examined.
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Hiroaki JIZOMOTO, Eri KANAOKA, Koichiro HIRANO
1989 Volume 37 Issue 7 Pages
1895-1898
Published: July 25, 1989
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This study was concerned with whether drug-entrapping liposomes can be prepared by using lyophilized, empty dipalmitoylphosphatidylcholine (DPPC)-liposomes. It was found that drug-entrapping liposomes could be prepared by warming a mixture of lyophilized empty DPPC-liposomes and aqueous drug solution over the solid-liquid crystal phase-transition temperature (T
c), indicating that warming (>T
c) resealed the defect in the bilayer membranes after incorporation of the drug into the empty liposomes. The pharmaceutical potential of this new method was examined, and the results proved that drug-containing liposomes could be prepared readily or immediately before use, and with reproducibly high efficiency (40-70%) of entrapment.
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Susumu KAWASHIMA, Michiyo SUGIMURA, Tatsumi NOGUCHI, Hiroshi FUJIWARA
1989 Volume 37 Issue 7 Pages
1899-1903
Published: July 25, 1989
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Rectal absorption of bacampicillin hydrochloride (BAPC) was found to show the best bioavailability with Witepsol H-15 as suppository base among various Witepsol bases. However, an effective plasma concentration of drug (above 0.5 μg/ml) was only maintained for 2 h, so sustained-release suppositories of BAPC were studied. Bacampicillin reacts with acidic polymer electrolytes such as pectic acid (Pc), chondroitin sulfate (Cd) and precipitates as its adduct with the polymer in an aqueous solution. The dissolution rate of BAPC from the adducts in a solution was slower than that of BAPC itself. The absorptions of BAPC from the suppositories containing the adducts were prolonged, but the bioavailabilities were decreased compared to that from the suppository containing BAPC alone.Similar prolonged absorption could be obtained simply by mixing Pc or Cd with BAPC in a base. Further, the absorption rate was found to be controlled by the amount of the polymer addition, and both a high plasma level and excellent bioavailability were obtained. This desirable outcome may be due to the simultaneous occurrence of rapid absorption of BAPC itself and formation of the adducts.
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Masa-aki MORI, Tadashi KAWAJIRI, Michio SAYAMA, Tatsuro MIYAHARA, Hiro ...
1989 Volume 37 Issue 7 Pages
1904-1908
Published: July 25, 1989
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The metabolism of 2, 4-dinitrotoluene (2, 4-DNT), 2, 4-dinitrobenzyl alcohol (2, 4-DNB), 2, 4-dinitrobenzaldehyde(2, 4-DNBAl), 2, 6-DNT, 2, 6-DNB and 2, 6-DNBAl in the microsomal and cytosol fractions prepared from unfortified male Wistar and male Sprague-Dawley (S.D.) rat livers was investigated. Data obtained by high-performance liquid chromatography (HPLC) indicated that the products of dinitrotoluenes (2, 4-DNT and 2, 6-DNT), dinitrobenzyl alcohols (2, 4-DNB and 2, 6-DNB), and dinitrobenzaldehydes (2, 4-DNBAl and 2, 6-DNBAl) in the microsomal and cytosol preparations containing nicotinamide adenine dinucleotide phosphate (NAD(P)) and reduced NAD(P)(NAD(P)H) were dinitrobenzyl alcohols (2, 4-DNB and 2, 6-DNB), dinitrobenzaldehydes (2, 4-DNBAl and 2, 6-DNBAl), and dinitrobenzoic acids (2, 4-DNBA and 2, 6-DNBA), and dinitrobenzyl alcohols (2, 4-DNB and 2, 6-DNB), respectively. From these results, it was concluded that the dinitrobenzaldehydes (2, 4-DNBAl and 2, 6-DNBAl) were intermediates in the oxidations of dinitrobenzyl alcohols (2, 4-DNB and 2, 6-DNB) to dinitrobenzoic acids (2, 4-DNBA and 2, 6-DNBA), and that the oxidations of dinitrobenzyl alcohols (2, 4-DNB and 2, 6-DNB) to dinitrobenzaldehydes (2, 4-DNBAl and 2, 6-DNBAl) and the reductions of dinitrobenzaldehydes to dinitrobenzyl alcohols (2, 4-DNB and 2, 6-DNB) were reversible The result of the consecutive oxidations of 2, 6-DNT in male Wistar rat livers, in the presence of various inhibitors suggests that oxidation of 2, 6-DNT to 2, 6-DNB is done mainly by microsomal cytochrome P-450, oxidation of 2, 6-DNB to 2, 6-DNBAl is mediated by microsomal cytochrome P-450 and nicotinamide adenine dinucleotide (NAD)-dependent alcohol dehydrogenase, oxidation of 2, 6-DNBAl to 2, 6-DNBA may be mediated by NAD-dependent aldehyde oxidase, and reduction of 2, 6-DNBAl to 2, 6-DNB may be mediated by reduced NAD(NADH)-dependent aldehyde reductase. From the comparative investigation of these reaction activities, it was found that : (a) the activity in the 2, 6-DNT oxidation to 2, 6-DNB was higher than that in the 2, 4-DNT oxidation to 2, 4-DNB in both strains, and the activity in Wistar rat was higher than that in S.D. rat; (b) the activities for the reductions of the dinitrobenzaldehydes (2, 4-DNBAl and 2, 6-DNBAl) to dinitrobenzyl alcohols (2, 4-DNB and 2, 6-DNB) were the highest, among the reactions examined, in both strains, and the reduction activity of 2, 4-DNBAl to 2, 4-DNB in Wistar rat was particularly high; (c) the activity for 2, 6-DNB oxidation to 2, 6-DNBAl was higher than that for 2, 4-DNB oxidation to 2, 4-DNBAl in both strains, and the activity in Wistar rat was higher than that in S.D. rat; (d) the activity for 2, 6-DNBAl oxidation to 2, 6-DNBA was much less than that for 2, 4-DNBAl oxidation to 2, 4-DNBA in both strains, and in particular, the activity for oxidation of 2, 6-DNBAl to 2, 6-DNBA in Wistar rat was low. The present results indicate that the metabolism of DNT isomers differs in different strains of rat.
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Takefumi MOMOSE, Osamu MURAOKA, Norihiko SHIMADA, Chikako TSUJIMOTO, T ...
1989 Volume 37 Issue 7 Pages
1909-1912
Published: July 25, 1989
Released on J-STAGE: March 31, 2008
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The stereochemistry in determining the migratory aptitude in the ring-expansion of bicyclo[3.3.1]nonane-2, 6-dione 6-ethylene acetal (7) is discussed. The Tiffeneau-Demjanov ring-expansion of 6β-aminomethyl-6α-hydroxy-bicyclo[3.3.1]nonan-2-one 2-ethylene acetal (5, endo-alcohol) gave the homologous ketones (13 and 14) in the ratio of ca. 8 : 1, together with the endo-oxide (8). The reaction of the epimeric isomer, 6α-aminomethyl-6β-alcohol (6, exo-alcohol) gave the ketones 13 and 14 in the ratio of 2 : 1. The difference in the selectivity between two epimers was well interpreted in terms of least motion theory and the conformational stability of the intermediates. Hydrolysis of 13 and 14 led to two novel tricyclic systems, an isotwistane (15) and a protoadamantane (17), respectively.
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Katashi MATSUMOTO, Hisashi MIYAZAKI, Toshihiko FUJII, Masahisa HASHIMO ...
1989 Volume 37 Issue 7 Pages
1913-1915
Published: July 25, 1989
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Binding of zonisamide, a new antiepileptic sulfonamide derivative, was examined to human erythrocytes, their lysate and their carbonic anhydrase by centrifugation for cells or by ultrafiltration for the others. Scatchard plots revealed that the binding to intact and lysed cells was composed of high- and low-affinity components and that to carbonic anhydrase, of the high-affinity component alone. Parameters for high-affinity binding were similar in all three preparations and those for low-affinity binding were similar in the former two preparations. Dissociation constants for these bindings to erythrocytes were smaller than the dissociation constant for serum albumin. These results may explain the concentration of sulfonamides in red cells, and suggest the participation of cellular protein component(s) in addition to previously known carbonic anhydrase in the binding.Acetazolamide, sulthiame, zonisamide, hydrochlorothiazide and sulfanilamide inhibited carbonic anhydrase in a non-competitive manner to different extents. The K
i values of these sulfonamides were of the order of 0.1-0.2 of their respective K
d values determined by ultrafiltration, suggesting that under the present conditions, physicochemical interactions between sulfonamides and carbonic anhydrase primarily occur at common sites that affect the activity of the enzyme.
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Hitoshi TANAKA, Masaya ISHIHARA, Kazuhiko ICHINO, Norihiro OHIWA, Kazu ...
1989 Volume 37 Issue 7 Pages
1916-1918
Published: July 25, 1989
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The reaction of 3-benzyloxy-4-hydroxy-2-methoxyxanthone with ethyl-2-bromo-3-(4-benzyloxy-3-methoxyphenyl)-3-oxopropionate in the presence of potassium tert-butoxide afforded the condensation product (8) which was converted to the debenzylation product (9) by hydrogenolysis. Reduction of 9 with lithium borohydride followed by treatment of resulting alcohols (10a, b) with concentrated hydrochloric acid in acetic acid provided kielcorin.
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