Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Volume 26, Issue 11
Displaying 1-50 of 55 articles from this issue
  • TSUTOMU KAMEYAMA, MAKOTO UKAI, TOSHITAKA NABESHIMA
    1978 Volume 26 Issue 11 Pages 3265-3270
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    In order to elucidate the mechanism of difenamizole (DFZ)-induced inhibition of Straub tail reaction (STR), the relationship between biogenic amines and DFZ-induced inhibition of STR (DIS) was particularly investigated in this experiment. 10 mg/kg of apomorphine and 2 mg/kg of methamphetamine decreased the DIS (intraperitoneal and intracerebral injection of DFZ) significantly without producing marked STR. Intracerebral injection of 50 μg/mouse of 5-hydroxytryptamine increased the DIS without affecting STR. On the other hand, the DIS was developed markedly, whether or not mice were pretreated with L-dopa, propranolol, disulfiram, L-5-HTP, tetrabenazine, nialamide, isocarboxazid and tranylcypromine. These results suggest that the DIS might at least be modulated by the variation in the activity of either catecholamine or tryptamine in the central nervous system of mice. In addition, the action mechanism of DFZ on STR was different from that on nociceptive reaction reported previously.
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  • HIROAKI TSUKATANI, SADAJI YAMADA, MASANOBU FUJII, TOSHIKAZU AWAJI, MAS ...
    1978 Volume 26 Issue 11 Pages 3271-3280
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    A modified procedure for preparation of D-I was offered, and became possible preparation of highly purified material showing a single spot on thin-layer chromatography in a more effective manner. Further examinations on chemical characteristics of D-I involving assessments of functional groups by chemical inactivations treating with various agents were carried out. In Girard's separation, about 30% of depressor-activity was recovered in nonketonic fraction. By treatment with sodium borohydride, the hypotensive activity disappeared completely. It was abolished completely with treatment by hydrogen peroxide (0.1%) or permanganate, while the activity was recovered almost completely by treatment with ferric chloride. It was also damaged with bromine. D-I became substantially less active by treatment with succinic anhydride, and inactive by phenylisocyanate. By treatment with triphenylphosphine or diazomethane at cold D-I was unaffected. The attitudes of D-I against several spray reagents on TLC were further examined, and it was found that 2, 4-dinitrophenylhydrazine-ferricyanide, 2', 7'-dichlorofluorescein and others were useful for detection of D-I. Generally, absorptional pattern of D-I in infrared spectrum resembled that of lysophosphatidyl choline. D-I might be a choline-containing phospholipid having double bond, free hydroxyl, ester, whereas it has no free amino, free carboxyl, amide, peroxide nor vicinal hydroxyl group, and it might have no carbonyl group other than ester. However, it might be convertible readily to a ketonic compound by some causes.
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  • HIROAKI TSUKATANI, SADAJI YAMADA, KENKICHI TAKAUCHI, AKIRA TOKUMURA, H ...
    1978 Volume 26 Issue 11 Pages 3281-3288
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    Stability of D-I preparation on standing at low temperature was examined. Standing in saline solution at 4°, the hypotensive activity was stable for the first 45 days, and lost completely within a following week. Standing as CHCl3-MeOH (2 : 1, v/v) solution at 4°, the decomposition began at 75 days later, and it reached a plateau maintaining about 20% of the initial activity. At-20°as a syrup form, the activity could be stored unaltered for 120 days. In the partition experiments, n-hexane and ethylether could extract little active component at all pH values tested (pH 4, 7 and 10). While n-butanol or Folch's solvent could extract unilaterally without any pH effects. The nuclear magnetic resonance spectrum of D-I strongly resembles that of lysophosphatidyl choline (LPCh). Specific optical rotation was also similar to that of LPCh. In the assessment of molecular weight on Sephadex LH-20 column eluting with 80% EtOH, the active substance was eluted in the neighbourhood of L-dipalmitoylphosphatidyl choline or L-1-palmitoyl-LPCh and its molecular weight was estimated to be about 500 to 800. In the analysis, the ratio of phosphorus, glycerol, choline and fatty acid was approximately 1 : 1 : 1 : 1, and oleic acid shared about half of the fatty acid composition. D-I might be a LPCh or closely related compound to it.
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  • SUSUMU ISHIMITSU, SADAKI FUJIMOTO, AKIRA OHARA
    1978 Volume 26 Issue 11 Pages 3289-3295
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    The mechanism of inactivation of papain by ascorbic acid in the presence of cupric ions was investigated. Dehydroascorbic acid and hydrogen peroxide which were oxidative product of ascorbic acid, were much less effective. In addition, bubbling nitrogen gas and radical scavengers prevented the inactivation by ascorbic acid and cupric ions. The results indicated that the inactivating effect of ascorbic acid was oxygen dependent and caused by free radicals formed during the autoxidation of ascorbic acid. The N-terminal amino acid and polyacrylamide disc gel electrophoretical patterns of the inactivated papain did not so differ from those of the native papain. On the other hand, the amino acids composition and fluorescence spectrum were changed in the inactivated papain as compared with the intact papain. These facts suggest that the cleavage of the S-S bond of papain molecule produced by the treatment with ascorbic acid and cupric ions resulted in inactivation.
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  • MAKOTO SATO, HIROAKI TAGAWA, AKIRA KOSASAYAMA, FUMIHIKO UCHIMARU, HIRO ...
    1978 Volume 26 Issue 11 Pages 3296-3305
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    In order to search for new psychotropic agents, several 1-butanone derivatives (VIII) substituted by pyridine, indole or quinoline were synthesized. And the carbonyl group of VIII was modified to methylene (XII), secondary alcohol (XIII) and vinyl (XIV). The effects of the compounds on spontaneous motor activity and rotarod test in mice were determined. The structure-activity relationships of these derivatives are discussed.
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  • KOUHEI YAZAWA, KAZUHIRO IMAI, ZENZO TAMURA
    1978 Volume 26 Issue 11 Pages 3306-3311
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    Oligo-and poly-saccharides which are utilizcd only by B. infantis and B. breve and not by other intestinal bacteria such as E. coli, L. acidophilus, and S. faecalis were investigated in vitro for the purpose of producing bifidus-flora in human intestines. Raffinose, stachyose, and inulin were found to be specifically utilized by B. infantis and doubling time of the cells with them as energy source was as short as with glucose and lactose. Inulin of molecular weight higher than ca. 4500 was not utilized by B. infantis. Oligosaccharides more than trisaccharide from inulin and tri-to penta-saccharides from dextran obtained by acid hydrolysis followed by Sephadex gel chromatographic separation were utilized specifically by B. infantis, but oligosaccharides from amylose and cellulose were found nonspecific for B. infantis and B. breve. Suitability of sugars for producing bifidusflora in vivo is discussed.
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  • YOICHI SUGAWARA, MICHIO FUJIHARA, YUJI MIURA, KOKICHI HAYASHIDA, TADAO ...
    1978 Volume 26 Issue 11 Pages 3312-3321
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    The species differences in the metabolism of naproxen [(+)-6-methoxy-α-methyl-2-naphthaleneacetic acid] were investigated in 6 species of animals and man. 3H-naproxen was orally administered to mice, rats, rabbits, guinea pigs, dogs and miniature pigs (OHMINI-875) and cold naproxen to human subjects, and their urinary and biliary (rats only) metabolites were separated and characterized by thin-layer chromatography, gas chromatography, high-performance liquid chromatography and gas chromatographymass spectrometry. The excretion rates as % of dose of naproxen and its metabolites in the 24 hr urine were, in a decreasing order, miniature pig 82.5, mouse 80.4, rat 74.7, rabbit 70.3, guinea pig 48.5 and dog 23.0%. Naproxen and its metabolites, i.e., 6-hydroxy-α-methyl-2-naphthaleneacetic acid (6-DMN), naproxen glucuronide, 6-DMN glucuronide and 6-DMN sulfate, were found in the urines of all species. Urinary naproxen in the rat was only 0.2% and those in the other species of animals were 4.8-13.7% of the urinary radioactivity, while in man it was 1.3% of dose. The main urinary metabolite in rat, guinea pig, dog, mouse and rabbit was 6-DMN sulfate (87.3, 46.7, 42.9, 39.9 and 36.2% of the urinary radioactivity, respectively), while those in man and miniature pig were naproxen glucuronide (25.3% of dose) and 6-DMN (78.6% of the urinary radioactivity), respectively. The animals whose urinary metabolic profiles were the nearest to that of man were the guinea pig and mouse, while the animals that differed most from man in this regard were the rat and miniature pig.
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  • HIROMICHI TANAKA, TAKAKO TAKAHASHI, HIROYUKI TOGASHI, TOHRU UEDA
    1978 Volume 26 Issue 11 Pages 3322-3329
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    Starting from 1-β-D-ribofuranosyl-2-oxo-4-imidazoline-4-carboxylic acid (1), obtained from uridine, various 2, 5'-O-cycloimidazole nucleosides have been prepared. The 2-oxo function of 1 was also converted to the 2-chloro and 2-thione functions. Whereas the circular dichroism (CD) spectra of 1 and related 2-oxo derivatives exhibited negative bands, their 5-bromo derivatives showed positive bands. All 2, 5'-O-cycloimidazole nucleosides showed strong negative CD bands which were in contrast to the results in the 8, 5'-O-cyclopurine nucleosides. The relationship between the sign of the CD bands and the orientation of the base moieties in imidazole nucleosides was discussed.
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  • MASAYUKI ONDA, YOSHIHIRO HARIGAYA, JUNYA HORIE
    1978 Volume 26 Issue 11 Pages 3330-3337
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    The 2-methyl ketone (2a, b), which are derived from the ketones (1a, b), afford the cis-imines (7a, b) and trans-imines (8a, b) by the Leuckart and Bischler-Napieralski reactions. Their methiodies (9a, b and 10b) are converted into the cis-lactams (15a, b) and trans-lactam (17b) via oxidation of the pseudo cyanides (14a, b and 16b). Bromination and successive dehydrobromination of 2a give the enone (20) which affords the cis-imine (23) and trans-imine (24) by the same procedure as above. The cis-methiodide (25) of 23 is reduced to give the cis-amine (26). The cis-lactams (15a, b) and cis-amine (26) can be connected with the synthetic methods of corynoline analogues, which were already known.
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  • NAMHO CHEI, TERUFUMI SAKAMOTO, TOKUHIKO HIGASHI
    1978 Volume 26 Issue 11 Pages 3338-3346
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    Messenger ribonucleic acid (mRNA) directing the biosynthesis of catalase [EC 1.11.1.6] was purified from bovine liver. The procedure consists of : (1) isolation of catalase-synthesizing polysomes by immunoprecipitation, (2) extraction of RNA from the polysomes with phenol, and (3) isolation of catalase mRNA by oligo (dT)-cellulose chromatography. Purified catalase mRNA has a molecular weight of 4-5×105 determined by electrophoresis on polyacrylamide-agarose gel. The mRNA stimulated catalase synthesis in a cell-free system derived from wheat germ ; i.e., the incorporation of 14C-amino acids into catalase increased proportionally to the amount of mRNA added in the cell-free system and with incubation time. On SDS-polyacrylamide gel the radioactivity peak of the cell-free products precipitated by anti-catalase antibody coincided with the migration of carrier catalase. In translating system the mRNA preparation directed the incorporation of 14C-amino acids into catalase at least 79% as efficiently as into total proteins.
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  • AKIRA MIWA, MASANORI YOSHIOKA, ZENZO TAMURA
    1978 Volume 26 Issue 11 Pages 3347-3352
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    Preparation of the antibody for radioimmunoassay of epinephrine was examined and an antibody with proper titre was obtained. A procedure for radioimmunoassay of epinephrine was developed by use of a membrane filter to separate bound and free hapten. The dose-response curves of analogs of epinephrine obtained by this method showed that the specificity of the antibody to epinephrine was sufficiently high : The 50% inhibition value of epinephrine was 1 pmol, those of metanephrine and synephrine were 80 pmol and those of norepinephrine and dopamine were 6×102 pmol. The result indicates that the antibody recognizes not only the side chain but also the catechol moiety of the hapten. The sensitivity of this radioimmunoassay was high enough to determine 0.1 pmol of epinephrine.
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  • TOSHIAKI NISHIHATA, NOBORU YATA, AKIRA KAMADA
    1978 Volume 26 Issue 11 Pages 3353-3363
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    Pharmacokinetic behavior of chlorpropamide (CPA) and sulfadimethoxine (SDM) following intravenous administration were studied in rabbits under normal and alloxan diabetic condition. Plasma concentration of both drugs in the β phase in diabetic rabbits sustained a higher level than those under normal condition. The abnormal pattern of the concentration-time curve of SDM recovered to the normal pattern by the 5-day insulin treatment, but CPA was not the case. Renal clearances of CPA, SDM and N4-acetylsulfadimethoxine (N4-AcSDM) were found to be decreased under diabetic condition. The decreased renal clearances of CPA and N4-AcSDM were subjected to the blockade of proximal tubular secretion of both drugs and to the increased renal tubular reabsorption due to urinary acidification under diabetic condition. The decreased renal clearance of SDM was subjected to the increased renal tubular reabsorption alone. Plasma protein binding and distribution into red blood cells of the drugs were also studied under normal and diabetic conditions.
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  • MITSUTAKA NATSUME, MORITAKA WADA, MASASHI OGAWA
    1978 Volume 26 Issue 11 Pages 3364-3372
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    Sensitized photooxidation of 5-cyano-1, 2-dihydropyridine derivative (3) afforded a crystalline and reactive endo-peroxide (4), and sulfur derivatives (5 and 6) as well as oxygen derivatives (9 and 10) were produced in good yield from this singlet oxygen adduct (4). 2-Methoxy derivative (9b) was found to be a good intermediate for production of 4-substituted compounds such as 5, 6, 7, 8, and 10, and 1-O-methyl-5-benzamido-5-deoxy-allopiperidinose (15a) and 1-O-methyl-5-benzamido-5-deoxyaltropiperidinose (17a) were synthesized from 13, which was obtained by the cis-dihydroxylation reaction of 9b. Formation of 9 from 4 was proved to be a multi-step reaction through 23 and 26.
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  • MASASHI TOMODA, CHIEKO ODAKA
    1978 Volume 26 Issue 11 Pages 3373-3377
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    A mucous polysaccharide, named Lilium-Ma-glucomannan, has been isolated from the bulbs of Lilium maculatum THUNB. It was homogeneous on glass-fiber paper electrophoresis and by ultracentrifugal analysis. The component sugars of the glucomannan were D-mannose and D-glucose in the molar ratio of 7 : 4, and its molecular weight was measured at 184000. Methylation, periodate oxidation, and partial acetolysis studies suggested that the polysaccharide is mainly composed of β-1→4 linked aldohexopyranose residues and it contains about seven aldohexose units per one end group on the average. D-Mannose units occupy non-reducing terminal positions and branching points linked through positions 2 or 3. The O-acetyl groups in the glucomannan were identified and determined as the content of 4.7%. They were located in positions 2, 3, 6, 3, 6, and 2, 3, 6 of a part of D-mannose units, and 6 and 2, 3, 6 of a part of D-glucose units.
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  • TOSHIAKI NISHIHATA, NOBORU YATA, AKIRA KAMADA
    1978 Volume 26 Issue 11 Pages 3378-3383
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    A study was made on the mechanisms of increased renal tubular reabsorption of chlorpropamide, sulfadimethoxine and N4-acethylsulfadimethoxine in diabetic rabbits. Urinary acidification with NH4Cl increased the renal tubular reabsorption of the drugs. Reabsorption coefficients of undissociated and dissociated molecules of the drugs were calculated using data of renal clearance of the drugs in alloxan diabetic rabbits and in NH4Cl-treated rabbits. Excellent accordance of the reabsorption coefficients as well as apparent reabsorption ratios in diabetic rabbits with those in NH4Cl-treated rabbits was observed. It was concluded that renal tubular reabsorption of drugs depended exclusively on the urinary pH in the renal tubules. Parameters of renal tubular reabsorption in vivo could be well expressed by the parameters of distribution between CHCl3-CCl4 (1 : 1 by volume) containing soy bean lecithin and buffer solution.
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  • HIROYUKI INOUYE, SHINICHI UEDA, SHINICHI UESATO, KOJI KOBAYASHI
    1978 Volume 26 Issue 11 Pages 3384-3394
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    Administration of labeled compounds such as [10-3H]-10-hydroxygeraniol (8), [10-3H]-and [11-3H2]-iridodial (7), [10-3H]-and [11-3H2]-iridodial glucoside (9) to Lamium amplexicaule, Deutzia crenata and Galium spurium var. echinospermon established that lamioside (1), deutzioside (2), scabroside (3), ipolamiide (4), lamiide (5) and asperuloside (6) are biosynthesized in these plants via 10-hydroxygeraniol (8) and iridodial (7).
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  • AKIRA KAMEI, NORIKO TAKEUCHI, SHUZO AKASHI, KOSHIRO KAGABE
    1978 Volume 26 Issue 11 Pages 3395-3403
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    An extracellular polysaccharide (referred to as Ps-III), which showed a positive immune activity to anti-Ps-III-sera obtained from a rabbit immunized with Escherichia coli 29M organisms, was isolated from the culture broth of E. coli 29M. By methylation, Smith degradation, partial acid hydrolysis and methanolysis of Ps-III, its repeating structure was postulated as given below : [numerical formula]
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  • HIROSHI YAMANAKA, TAKAO SAKAMOTO, YUMI BANNAI, SHIGERU OGAWA
    1978 Volume 26 Issue 11 Pages 3404-3409
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    Unlike quinoline and isoquinoline N-oxides, 4, 6-dimethylpyrimidine 1-oxide reacted with active methylene compounds such as malononitrile, ethyl cyanoacetate, and ethyl ethoxycarbonylacetimidate to give ring-opened products. In these cases, none of pyrimidine derivatives with a substituent at the 2-position were isolated. On the other hand, the pyrimidine 1-oxide was condensed with 5-amino-3-methyl-isoxazole to give 2-(5-amino-3-methyl-4-isoxazolyl)-4, 6-dimethylpyrimidine. Comparing these two reactions, the driving force of the ring-fission of the reaction intermediates was discussed.
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  • MORIO KIYOZUMI, SHOJI KOJIMA
    1978 Volume 26 Issue 11 Pages 3410-3415
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    The excretion of cadmium through the bile and gastrointestinal mucosa after the intraperitoneal administration of cadmium chloride and the effect of the chelating agents such as citric acid, D-cysteine, and DL-penicillamine on its excretion were studied in rats pretreated with cadmium. Cadmium pretreatment caused an appreciable decrease in the biliary excretion of subsequently administered cadmium and had no effect on the excretion of the metal through the gastrointestinal mucosa. The chelating agents used had no stimulatory effect on the biliary excretion of cadmium and scarcely affected the excretion of the metal through the gastrointestinal mucosa in the pretreated rats. Moreover, a mechanism of the effect of cadmium pretreatment on the excretion of cadmium through the bile in rats was investigated. From findings relating to the contents of cadmium and zinc in the liver and kidney, the biliary and urinary excretion of both metals, and the binding characteristics of both metals to different proteins in the supernatant of liver, it was suggested that a part of subsequently administered cadmium replaced the zinc bound to metallothionein synthesized in the liver by the pretreatment, resulting in a decrease in the biliary excretion of cadmium and no stimulatory effect of the chelating agents on its excretion.
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  • SHUJI TAKAHASHI, EIICHI KITAZAWA, AKIRA OGISO
    1978 Volume 26 Issue 11 Pages 3416-3418
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    (±)-Ligantrol (10), isolated from Liatris elegans, was synthesized from the hypothetical precursor, 18-hydroxygeranylnerol (2) which was a isomer of 18-hydroxygeranylgeraniol (1) isolated from Croton sublyratus as an antigastric ulcer principle.
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  • YOSHINOBU NAKAI, SHINICHIRO NAKAJIMA, KEIJI YAMAMOTO, KATSUHIDE TERADA ...
    1978 Volume 26 Issue 11 Pages 3419-3425
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    Several drugs, such as benzoic acid, aspirin, salicylic acid, and methyl p-hydroxy benzoate, all of which had intermolecular hydrogen bondings, were ground with microcrystalline cellulose respectively. Each drug was ground with β-cyclodextrin too. The inclusion compounds of each drug with β-cyclodextrin were prepared from aqueous solution. When the drugs were ground with β-cyclodextrin, rapid disappearance of X-ray diffraction peaks and that of heat of fusion of drugs, compared with microcrystalline cellulose, were observed. About the inclusion compounds, it was concluded from X-ray diffraction, thermal analysis, and ultraviolet measurements that β-cyclodextrin formed 1 : 1 adduct with each drug and the drug molecules were preffered oriented. The conditions of the drug molecules in the ground mixtures and in the inclusion compounds were investigated using infrared spectroscopy, especially by monitoring the carbonyl stretching bands near 1700 cm-1. When the dispersion of drugs into matrices were completed, the distinct frequency shift of the carbonyl stretching bands was observed in the infrared spectra of these sample. From these results, it would be reasonable to consider that in the ground mixture of microcrystalline cellulose, the drug molecules were present monomolecularly, presumably interacting with cellulose molecules by hydrogen bondings.
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  • TAKU CHIBA, SETSUZO TEJIMA
    1978 Volume 26 Issue 11 Pages 3426-3432
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    The titled new reducing disaccharides were synthesized from a derivative of lactose. When 1, 6-anhydro-4-O-(2, 3-anhydro-4, 6-O-benzylidene-β-D-glucopyranose (2) was treated with boiling methanolic sodium methoxide, or LiAlH4 in boiling tetrahydrofuran, the trans-diaxial cleavage of the epoxide ring proceeded predominantly according to the Furst-Plattner rule. This agreed with the result obtained by treatment of 2 with KOH, reported previously [T. Chiba and S. Tejima, Chem. Pharm. Bull. (Tokyo), 25, 1049 (1977)]. After acetylation, the major and minor cleavage products of epoxide were isolated by column chromatography on silica gel. The structural assignments of individual products were described. The titled disaccharides were respectively prepared from the individual major product via a series of the following reactions : debenzylidenation, acetylation, opening of the 1, 6-anhydro ring, and removal of the acetyl groups.
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  • HITOSHI MATSUMOTO, YOSHITERU OHKURA
    1978 Volume 26 Issue 11 Pages 3433-3439
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    The π-π* absorption spectra of some psoralens with skin photosensitizing action were measured in various solvents, up to vacuum ultraviolet region. We found that these compounds exhibit six π-π* bands within 180-400 nm region and the longest wavelength absorption band of psoralen shows a blue shift with increasing polarity of the solvents. Furthermore, the molecular orbital calculation of the π-electronic systems of psoralens were carried out by means of the Pariser-Parr-Pople method. The obtained absorption π-π* bands were assigned on the basis of the calculated results.
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  • HIDEAKI UMEYAMA, KAZUYOSHI TAKEDA, HARUO OGURA, IKUO MORIGUCHI, AKIRA ...
    1978 Volume 26 Issue 11 Pages 3440-3443
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    In order to elucidate origin of the Cotton effect of ε-caprolactam, the molecular orbital studies were performed by using the MO's obtained from the CNDO/2 method. It was shown that the sign of the n-π carbonyl Cotton effect for ε-caprolactam is due to the electronic structure of the neighboring carbon of the carbonyl group and the delocalization energy between-CONH-group and the two methylene groups of C (3) H2 and C (5) H2.
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  • NORIO AIMI, KEIICHI YAMAGUCHI, SHINICHIRO SAKAI, JOJU HAGINIWA, AKINOR ...
    1978 Volume 26 Issue 11 Pages 3444-3449
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    ^<13>C-NMR spectra of several Gardneria alkaloids and their derivatives were studied. The chemical shifts of C(15) and C(21) were found to be diagnostic for the configuration of the side chain double bonds between C(19) and C(20). As a result of the present study the E configuration of the ethylidene side chain of chitosenine (V) was confirmed.
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  • SHIGEO IKEGAWA, NORIKO OBATAKE, HIROSHI HOSODA, TOSHIO NAMBARA
    1978 Volume 26 Issue 11 Pages 3450-3456
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    In order to clarify the metabolic fate of hydrogen at C-2 during microbial transformation of dehydroepiandrosterone into 1α-hydroxy-4-androstene-3, 17-dione, the stereospecific synthesis of epimeric 2-d1-dehydroepiandrosterones have been undertaken. A key intermediate leading to the required substrates, 5α-androst-2-ene-6β, 17β-diol 17-tert-butyl-dimethylsilyl ether, was prepared from dehydroepiandrosterone in several steps. Deuterioboration of the Δ2-olefin and subsequent oxidation of the organoborane afforded the 2α-deuterio-3α-ol. The trans-diaxial opening of the 2α, 3α-epoxide with lithium aluminum deuteride provided the 2β-deuterio-3α-ol. Being submitted to dehydration with phosphorus oxychloride in pyridine followed by usual elaborations, the C-2 deuterated 6β-hydroxysteroids were converted to the desired 2-d1-dehydroepiandrosterones.
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  • HIDEO NAKAMACHI, ISAMU AOKI, HIROYUKI ASAKAWA
    1978 Volume 26 Issue 11 Pages 3457-3462
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    3-(4-Carbamoyl-1-pyridiniomethyl)-7β-(D-α-sulfophenylacetamido)-ceph-3-em-4-carboxylate monosodium (cefsulodin sodium) was found to exist in crystals in three states of hydration. The hexahydrate was obtained by crystallization from aqueous ethanol and was dehydrated to the dihydrate and anhydrate. The properties of the crystal water in cefsulodin sodium were investigated.
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  • JUN WATANABE, AKIO KOZAKI
    1978 Volume 26 Issue 11 Pages 3463-3470
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
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    According to the previously proposed model for drug distribution in the body, the apparent volumes of distribution (Vd') of basic drugs with high apparent partition coefficients (P') were related to the blood plasma volume, the other non-lipid space, and the lipid space. The logarithm of Vd' values for basic drugs with P' of 3.2×100-6.7×102 had good correlation (r=0.937) with the logarithm of P'values. The relationship between Vd' and P' was estimated in the region of both low and high P'. The comparison of the result with the observed values indicated that the proposed model was considerably satisfactory, but that there were some other factors which fluctuated the values of Vd'.
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  • KIYOSHI ZAITSU, HIDEAKI NAGAI, KENJI OHTSUBO, SEIJI ETO, KAZUYA KOHASH ...
    1978 Volume 26 Issue 11 Pages 3471-3476
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    An assay method of human platelet monoamine oxidase is presented based on the fluorometric determination of benzaldehyde formed from the substrate benzylamine under the optimal enzyme reaction conditions by the 1, 2-diaminonaphthalene method. This method is very sensitive and permits the assay even with 50 μg of platelet protein. The method was successfully applied to the assessment of inhibitory effect of monoamine oxidase inhibitors (tranylcypromine, pargyline, iproniazid, nialamide, isoniazid and cuprizone).
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  • KANETO UEKAMA, FUMITOSHI HIRAYAMA, SHOUZO NASU, NAOKI MATSUO, TETSUMI ...
    1978 Volume 26 Issue 11 Pages 3477-3484
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    Stability constant (Ke) for 1 : 1 inclusion complexes of α-and β-cyclodextrins with barbiturates, phenothiazines, sulfonylamides, and sulfonylureas were determined by high performance liquid chromatography (HPLC). The retention times of the drugs following the binding to cyclodextrins in aqueous mobile phase on ion exchange support were quantitatively treated to obtain the Ke values. The Ke values obtained by HPLC method were in fair agreement with those obtained by other methods such as solubility and spectroscopic methods. The advantages of HPLC method developed here were that Ke values could be rapidly obtained by simple procedure with minimum quantity of the drugs and reproducibility and accuracy were not less than other methods. Furthermore, this method was proved to be particularly suitable for chemically unstable compounds such as phenothiazines.
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  • TAKEO HIGASHINO, KIYOSHI SUZUKI, EISAKU HAYASHI
    1978 Volume 26 Issue 11 Pages 3485-3491
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    Both the reactions of 3, 4-dihydro-4-quinazolinylmethyl alkyl ketones (4) with active methylene compounds or ketones (NuH) without a catalyst and in the presence of alumina as a catalyst were carried out, and resulted in the transformation of 4 into quinolines (3). Thus 2-(3, 4-dihydro-4-quinazolinyl) acetophenone (4a), 2-(3, 4-dihydro-4-quinazolinyl)-cyclohexanone (4b), and 1-(3, 4-dihydro-4-quinazolinyl)-2-propanone (4c) reacted with diethyl malonate (NuH-2), phenylacetonitrile (NuH-3), acetophenone (NuH-4), cyclopentanone (NuH-5), and cyclohexanone (NuH-6) without catalyst to give 2-phenylquinoline (3b), 1, 2, 3, 4-tetrahydroacridine (3c), and 2-methylquinoline (3d), respectively, together with the dissociation product, quinazoline (1a), although the yield of 3 was very poor. Alumina as a catalyst accelerated these reactions to give 3 in moderate yield. Even the reaction with chloroform (NuH-7) and ethyl orthoformate (NuH-8) gave 3 in good yield. The phenyl and methyl groups substituted at the 2-position prevented 4 from transforming into 3 in both the reactions without a catalyst and in the presence of alumina. A similar transformation was also found between 4, 5-dihydro-5-hydroxy-1-methyl-1H-pyrazolo [3, 4-d] pyrimidine-4-malononitrile (5) and NuH in the presence of alumina, and resulted in the formation of 6-amino-1-methyl-1H-pyrazolo [3, 4-b] pyridine-5-carbonitrile (8). The possible mechanism of the reaction was discussed.
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  • TAKUJI DOI, TSUNETAKA NAKAJIMA, MASAYUKI NISHIDA, TADAKAZU SUYAMA
    1978 Volume 26 Issue 11 Pages 3492-3497
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    Three gamma-globulin (IgG) preparations were prepared by enzymatic digestion with plasmin [IgG (plasmin)] or pepsin [IgG (pepsin)] and by polyethylene glycol (PEG) fractionation [IgG (PEG)] and their efficacy was compared in terms of the ability to promote phagocytosis in vitro of three strains of pyogenic bacteria, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae, by human polymorphonuclear leukocytes. IgG (plasmin) had the composition of IgG : Fab : Fc=60 : 26 : 14 ; IgG (pepsin), IgG : F (ab')2 : Fc=8 : 77 : 15 and IgG (PEG), 90% or more IgG. In the phagocytosis test, IgG (PEG) was the most efficient and IgG (plasmin) more than IgG (pepsin) though agglutinin titers of these were much the same. The F (ab')2 fragments were almost inefficient in spite of their agglutinin titer similar to those of the IgG preparations. The Fab and Fc fragments showed neither agglutinin titer nor the ability to promote phagocytosis. Since it has been confirmed by a previous study (ref. 16) on the phagocytosis mechanism that these differences in phagocytic effects result from a phagocytotic mechanism in which antigen bound to antibody at its Fab portion is phagocytized through receptors for Fc and complement present on the polymorphonuclear leukocyte surface, it may be concluded that an IgG preparation desirable for clinical use is that which contains intact IgG molecules as much as possible.
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  • HITOSHI UNO, MIKIO KUROKAWA
    1978 Volume 26 Issue 11 Pages 3498-3503
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    The site of the electrophilic substitution of 1, 2-benzisoxazole-3-acetic acid (1) altered depending on species of electrophiles and reaction conditions. In halogenation, only the α-methylene group of 1 was substituted. In the chlorosulfonation, the α-methylene group was substituted at first and then the 5-position of the nucleus was substituted. On the other hand, in the nitration, the 5-position was substituted at first and the α-methylene group was substituted secondly.
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  • KAZUHISA FUNAKOSHI, HIROTSUNE SONODA, YOSHIKO SONODA, MASATOMO HAMANA
    1978 Volume 26 Issue 11 Pages 3504-3514
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    The reaction of quinoline 1-oxide with ethyl cyanoacetate and acetic anhydride in dimethylformamide (DMF) or dimethylsulfoxide (DMSO) at low temperatures was found to give quinolinium-ethoxycarbonylcyanomethylide as the main product besides the normal 2-substituted and 4-substituted products. This novel formation of N-ylide was examined under various conditions, and the following features were revealed. Acetic anhydride was most effective as acylating agent, and DMF and DMSO seemed most suitable media for the N-ylide formation. In addition to ethyl cyanoacetate, malonodinitrile, methyl cyanoacetate and benzoylacetonitrile also produced the corresponding N-ylides, but other active methylene compounds such as malonates, ethyl acetoacetate and cyanoacetamide gave no ylide, only 2-substituted or/and 4-substituted products being formed. As for aromatic N-oxide, pyridine and isoquinoline N-oxides were inert to the N-ylide formation. On the other hand, quinoline 1-oxides bearing an electrondonating group at the 4-position, i.e., lepidine, 4-methoxy-and 4-amino-quinoline 1-oxides, were highly reactive toward this type of N-ylide formation. A likely reaction mechanism was proposed.
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  • YASUMITSU TAMURA, MOON WOO CHUN, SUNDO KWON, M.BAYOMI SAID, TOMOKO OKA ...
    1978 Volume 26 Issue 11 Pages 3515-3520
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    Reaction of benzo [b] furan with iodine azide gives in high yield a mixture of cis-and trans-2, 3-diazido-2, 3-dihydrobenzo [b] furans, both of which, upon treatment with alkali, are converted to 3-azidobenzo [b] furan. Similar reaction of 1-benzoyl-and 1-tosyl-indoles with iodine azide affords high yields of cis-and trans-1-benzoyl-and 1-tosyl-2, 3-diazidoindolines. Stereochemical assignment of the adducts is made on the basis of nuclear magnetic resonance spectroscopy.
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  • TAKEFUMI MOMOSE, TETSUAKI TANAKA, TAKASHI YOKOTA, NORIO NAGAMOTO, KAZU ...
    1978 Volume 26 Issue 11 Pages 3521-3529
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    The reaction of alkyl 3-hydroxypyrrole-2-carboxylates (1) with some electrophiles was investigated. The alkylation of 1c occurred at the O and C-2 position as in the case of usual β-keto esters. An N-substituted 3-hydroxypyrrole-2-carboxylate (1e) reacted at the 2-position upon the Michael reaction. In addition to the C-2 adduct (9), an unexpected 2, 2-bis-adduct (10) was concurrently obtained possibly via the ketonic cleavage of the mono-adduct (9) followed by the second addition of acrylate. The N-unsubstituted one (1b) gave a mono-adduct at C-2 (12) and a bis-adduct at C-2 and N (13). Upon bromination, 1c reacted at the 4-and 5-position, not at the 2-position ; namely 1c reacted with bromine as an enamine or a pyrrole, and not as a β-keto ester. The Mannich reaction occurred rapidly and selectively at the 4-position, and the 4-bromo derivative (15) reacted preferentially at the 5-position. In the cyanation of the quarternary salts of the Mannich bases, a dimer (23), a trimer (24) and a dicyano compound (26) were obtained in addition to the expected cyanides (22, 25).
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  • SATORU IKENOYA, TOSHIRO TSUDA, YOSHIAKI YAMANO, YOSHIHARU YAMANISHI, K ...
    1978 Volume 26 Issue 11 Pages 3530-3539
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    A flow cell electrochemical detector (ECD) using a glassy carbon electrode for high-performance liquid chromatography (HPLC) was designed and characterized. The ECD examined by us showed the same property as the tubular type electrode. The linear dynamic range of norepinephrine (NE), dopamine (DA) and serotonin (5HT) peak current were about 104 (50 pg-1 μg) and the minimum detectable quantities for NE and DA were 5 and 10 pg. High-performance reversed-phase chromatography in combination with ECD permitted the simultaneous determination of NE, DA and 5HT in a whole mouse brain and mouse cerebellum. Assay of NE, DA and 5HT gave the mean values of 430, 872 and 749 ng/g wet tissue for whole mouse brain, and 259, 16 and 240 ng/g wet tissue for mouse cerebellum.
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  • TOSHIAKI MIURA, TAKETO OGISO
    1978 Volume 26 Issue 11 Pages 3540-3545
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    The formation of methemoglobin (metHb) from oxyhemoglobin (oxyHb) in the erythrocyte by O2-was studied under the O2--generating system of photoactivated riboflavin with oxygen by using a catalase inhibitor, 3-amino-1, 2, 4-triazole (AT). In the AT-treated erythrocytes in vitro which have little catalase activity, the rate of metHb formation was increased remarkably compared with that of untreated normal erythrocyte. Furthermore, catalase added to 60 unit/ml to the suspending medium contained AT-treated erythrocytes caused a strong inhibition of formation of metHb, suggesting that H2O2 is generating in the external medium of erythrocytes by the reaction of photoactivated riboflavin or spontaneous dismutation of O2-. Addition of superoxide dismutase (5μg/ml) caused an acceleration but not inhibition of the metHb formation. Hemolysis was scarcely observed in the time course of this experiment. These results may be interpreted that H2O2 generated in the outside of cells moves across the membrane and results in oxidative attack to oxyHb in the erythrocyte without the hemolytic effect. Another possible participation of O2- may be suggested to exert its enhanced oxidation of oxyHb, namely that O2- generated in the outside of cells may pass through the membrane directly.
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  • TAKASHI ABIKO, MIHOKO KUMIKAWA, SACHIKO DAZAI, CHIKAKO UNO, MAKOTO ISH ...
    1978 Volume 26 Issue 11 Pages 3546-3551
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    The tetradecapeptide corresponding to position 1 to 14 of glucagon was synthesized by a conventional method. Though the suppression test of this peptide was tested against PHA-induced lymphocyte transformation, any reproducible and significant results were not obtained. In this finding, the effect on immunodeficiency of chronic renal failure was not because of glucagon fragment (1-14).
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  • KAZUAKI KUKINO, TAKASHI DEGUCHI
    1978 Volume 26 Issue 11 Pages 3551-3555
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    The anticonvulsant activity of sodium dipropylacetate (DPA) and its effects on the cerebral 5-hydroxytryptamine (5HT) and γ-aminobutyric acid (GABA) metabolisms in the reserpinized mice have been studied to know the mechanism of action of DPA. The results are as follows ; 1. DPA elevated the turnover of the cerebral 5HT and the content of the cerebral 5-hydroxyindoleacetic acid. Phenobartital sodium (PB) showed no effects. 2. DPA elevated the cerebral GABA content in the reserpinized mice. 3. In maximal electroshock seizure, the seizure-protecting activities of DPA and PB were lower in the reserpinized mice than in the normal. 4. In pentylenetetrazole seizure, the seizure-protecting activity of DPA in the reserpinized mice was the same as in the normal. In combined administration, L-di-hydroxyphenylalanine decreased the activity of DPA in the reserpinized mice. The activity of PB decreased in the reserpinized mice. From these results, it was suggested that DPA showed the anticonvulsant activity partially through its effect on the cerebral metabolism of 5HT as well as GABA.
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  • MITSURU FURUKAWA, TADASHI OHKAWARA, YOSHIHIDE NOGUCHI
    1978 Volume 26 Issue 11 Pages 3556-3558
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    The reactions of 2, 3-epoxypropylaryl ether with ethyl-N-phenylformimidate (I) and with N, N'-diphenylformamidine (II) were examined. It was found that the reactions gave the same product, N-(2-hydroxy-3-aryloxypropyl)-N-phenylformamide (III).
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  • KEISUKE KAWASHIMA, HIROSHI ITOH, ICHIRO CHIBATA
    1978 Volume 26 Issue 11 Pages 3558-3562
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    A rapid method for evaluating antioxidant activity was developed. By this method as many as twenty samples can be evaluated simultaneously. Moreover, the procedure is facile and gives quick result. The test system consisted of linoleate emulsion dispersed in phosphate buffer (pH 7.0) containing hemin. The rapid oxygen uptake due to hemin-catalyzed oxidation of linoleic acid was manometrically measured with a Gilson differential respirometer. The rate of decrease in the oxygen uptake was used for evaluating antioxidant activity of samples. The activity of browning products formed by the reaction between amino acid and sugar was determined by this method, and the results were compared with those obtained by the active oxygen method.
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  • TAI GI CHUNG, SETSUZO TEJIMA
    1978 Volume 26 Issue 11 Pages 3562-3564
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    The title branched trisaccharides were synthesized from 1, 2, 2', 3, 3', 4', 6'-hepta-O-acetyl-β-maltose (1). A modified Koenigs-Knorr condensation of 1 with 2, 3, 4, 6-tetra-O-benzyl-α-D-galactopyranosyl chloride or 2, 3, 4, 6-tetra-O-acetyl-α-D-galactopyranosyl bromide afforded a protected trisaccharide having α-D-or β-D-galactosidic linkage at the C-6 hydroxyl group in maltose, respectively. The yield was 37 or 52% from 1. The configuration of new galactosidic linkages in the trisaccharides was confirmed by comparison of the molecular rotation of their corresponding undecaacetates with the value of calculation. Deacetylation of the undecaacetates afforded the title trisaccharides.
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  • KUNIYOSHI SAKURAI, SAKAE AOYAGI, HATSUNORI TOYOFUKU, MINORU OHKI, TOYO ...
    1978 Volume 26 Issue 11 Pages 3565-3566
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    Selective N1-tetrahydrofurylation of uracils has been performed in satisfactory yield by direct addition of uracils to 2, 3-dihydrofuran in the presence of PCl5 in hexamethyl-phosphoramide (HMPA).
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  • AKIKO NAKAGAWA, RYOKO OHUCHI, ITSUO YOSHIZAWA
    1978 Volume 26 Issue 11 Pages 3567-3571
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    2, 3, 17 β-Trihydroxyestra-1, 3, 5 (10)-trien-6-one (7) and its methylated derivatives (6, 12, and 16) have been prepared for the biological investigation. The preparation method and the results of the instrumental analyses including nuclear magnetic resonance and ultraviolet spectra of these materials are described.
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  • YUTAKA HIGASHI, TOSHIAKI NISHIHATA, KAZUYOSHI KUBO, NOBORU YATA, AKIRA ...
    1978 Volume 26 Issue 11 Pages 3572-3576
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    Displacement of eight sulfonamides by sodium salicylate from the binding sites of bovine serum albumin (BSA) was studied by the equilibrium dialysis method at pH 7.4 and 37°. Amount of sulfonamides displaced by the addition of salicylate (1 or 3 mM) were linearly correlated with their amount bound to the binding sites of BSA in the absence of salicylate. Double-reciprocal plots of the binding of sulfamethoxazole to BSA with and without salicylate, following Langmuir's isotherms, resulted in linear curves with a common ordinate intercept. This result suggests that the inhibitory effects of salicylate on the binding of sulfamethoxazole to albumin were competitively performed at the same binding site on the protein.
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  • AKIRA TANAKA, TOSHINAO USUI
    1978 Volume 26 Issue 11 Pages 3576-3579
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    Seven kinds of 4-substituted 5-(5-nitro-2-furyl) thiazol-2-ones were obtained by the reaction of α-substituted β-(5-nitro-2-furyl) vinylamines (Ia-g) with chlorocarbonylsulfenyl chloride. Reaction of Ia and c with trichloromethylsulfenyl chloride gave 3-sub-stituted 4-(5-nitro-2-furyl)-5-chloroisothiazoles.
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  • NOBUTOSHI TANAKA, TAKAO MURAKAMI, YASUHISA SAIKI, CHIUMING CHEN, LUIS ...
    1978 Volume 26 Issue 11 Pages 3580-3582
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    Aus den oberirdischen Teilen von Pteris grandifolia L. wurden neben Quercitrin (3, 5, 7, 3', 4'-Pentahydroxy-flavon-3-mono-α-L-rhamnopyranosid) zwei neue Flavonol-acetyl-glykoside, d.h., 3"-O-Acetyl-quercitrin und 4"-O-Acetyl-quercitrin isoliert und identifiziert.
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  • CHIKARA KANEKO, REIKO HAYASHI, HARUE FUJII, ATSUSHI YAMAMOTO
    1978 Volume 26 Issue 11 Pages 3582-3584
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    The successful use of 3-sulfolene as an alternative reagent for sulfur dioxide was demonstrated for the first time by two types of the reactions : i) deoxygenation of aromatic amine N-oxides and ii) isomerization of ergosterol and its derivatives.
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  • KOTARO TAKAHASHI, MASAKO TAKANI
    1978 Volume 26 Issue 11 Pages 3585-3587
    Published: November 25, 1978
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    Irradiation of d-usnic acid at -20° under oxygen atmosphere afforded 2, 4-diacetyl-6-methyl-phloroglucinol (IV), together with racemic usnic acid, and decarbousnic acid afforded also the same compound under the same conditions. The mechanism of the photo-oxidation of usnic-and decarbousnic-acids was studied.
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