Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Volume 44, Issue 5
Displaying 1-48 of 48 articles from this issue
  • Shuji KITAGAWA, Yasuhiro SUGIYAMA, Takeshi SAKUMA
    1996 Volume 44 Issue 5 Pages 881-884
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    The effects of pyrocatechol and its monosubstituents on the hemolysis of bovine erythrocytes induced by the hydrophilic free radical initiator, 2, 2'-azobis(2-amidinopropane)dihydrochloride (AAPH), were investigated. Relatively hydrophilic derivatives such as the 4-COO- substituent (protocatechuic acid), which are almost completely ionized at physiological pH, have a more inhibitory effect than the more hydrophobic derivatives such as the 4-C(CH3)3 substituent. In the presence of relatively low concentrations of the latter derivatives, the onset of hemolysis was retarded, but the hemolysis then proceeded more rapidly and the time, at which almost complete hemolysis occurred, was almost the same as that in their absence. Regression analysis on the relationships between the inhibitory effects of the derivatives and their redox potentials and hydrophobic parameters revealed that the inhibitory activity of the catechol derivatives on AAPH-induced hemolysis was controlled by low hydrophobicity as well as electron donor activity. In the presence of relatively hydrophobic catechol derivatives, oxidation of hemoglobin was observed. These findings suggest that interaction of these derivatives with hemoglobin after their penetration into erythrocytes reduced the scavenging activity against free radicals. Their interaction with membrane or cytoplasmic components may cause the increased hemolysis rate after the onset of hemolysis at relatively low concentrations.
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  • Yasuhiro TANAKA, Tomikazu KAWANO, Saiful Md. ISLAM, Hiroyasu NISHIOKA, ...
    1996 Volume 44 Issue 5 Pages 885-891
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Biologically interesting ethyl 6-aryl-3-ethoxy-6-oxo-2, 4-hexadienoates (1) have been prepared by the Witting reaction of [3-(ethoxycarbonyl)-2-ethoxy-2-propenylidene]triphenylphosphoranes (3a and 3b) and -arsorane (3c) with glyoxal monohydrates (5) and by oxidation of 6-aryl-3-ethoxy-6-hydroxy-2, 4-hexadienoate (9) with activated manganese (IV) oxide supported by silica. Reaction of 1a with 3c gave 3-(4-chlorobenzoyl)-1, 2-trans (and cis)-bis(1-ethoxy-2-ethoxycarbonylethenyl)cyclopropanes (6 and 7). When 1a was treated with a 1 : 5 mixture of concentrated HCl and tetrahydrofuran at room temperature, 3-hydroxy-6-oxo-2, 4-hexadienoate (10a) was obtained in 46% yield. Treatment of 1b with trifluoroacetic acid gave 5, 6-dihydro-2H-pyran-2-one (12) in 53% yield together with 10b in 28% yield. When 1a was treated with 1N ethanolic potassium hydroxide, 12 and 2H-pyran derivative (13) were obtained in 33% and 28% yields, respectively. Reaction of 1a with ammonium hydroxide and primary amines in the presence of a proton acid gave 2-oxo-1, 2, 5, 6-tetrahydropyridines (14) in good yields. The mechanism of the formation of 6, 12, 13, and 14 is discussed.
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  • Norio SHIBATA, Chino FUJIMORI, Shigekazu FUJITA, Yasuyuki KITA
    1996 Volume 44 Issue 5 Pages 892-894
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Treatment of chiral, non-racemic vinyl sulfoxides with O-silylated ketene acetal in the presence of a catalytic amount of zinc chloride in tetrahydrofuran resulted in an enantioselective Pummerer-type reaction, affording a considerable yield of the corresponding enantiomerically enriched methyl 4-siloxy-4-sulfenylbutyrate in 78-82% ee.
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  • Naoki NODA, Ryuichiro TANAKA, Kazumoto MIYAHARA, Takayuki SUKAMOTO
    1996 Volume 44 Issue 5 Pages 895-899
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Six neutral glycosphingolipids were isolated in the pure state from the leech, Hirudo nipponica (Annelida). In contrast to the zwitterionic monogalactosylceramides carrying a choline phosphate group so far obtained, all compounds are non-zwitterionic glycosphingolipids, trigalactosylceramides. Five compounds possess a Galα1-6Galα1-6Galβ1-Cer core, and one is unique in having a Galα1-6Galβ1-6Galβ1-Cer structure. Their full structures have been determined on the bases of chemical and spectral evidence.
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  • Takushi KURIHARA, Yasuhiko SAKAMOTO, Tetsuya KIMURA, Hirofumi OHISHI, ...
    1996 Volume 44 Issue 5 Pages 900-908
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Eudistomins, isolated from the colonial tunicate Eudistoma olivaceum, have been a synthetic target due to their strong antiviral activity against Herpes simplesx virus (HSV-1) and activities against certain types of tumors in vivo. In order to examine the structure-activity relationship of eudistomins, 12-carbaeudistomin analogs were synthesized and their activities against influenza A and B virus, HSV-1, HSV-2 and human cytomegalovirus were investigated. Among them, racemic 6-methoxy-12-carbaeudistomin showed similar activity to (-)-debromoeudistomin K, synthesized as a control compound.
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  • Tetsuya TAKEYA, Shinobu YAMAKI, Toshimasa ITOH, Hiroko HOSOGAI, Seisho ...
    1996 Volume 44 Issue 5 Pages 909-918
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    We have established a new general synthesis for (±)-dibenzocyclooctadiene lignans, including (±)-schizandrin (1a), (±)-gomisin A (1b), (±)-isoschizandrin (3a), and (±)-isogomisin A (3b), via the spiro-dienone ethers E- and T-11 as the key intermediates, prepared from the corresponding bisarylbutanol derivatives E- and T-10 by the oxidation with Weitz' aminium salt, tris(4-bromophenyl)aminium hexachloroantimonate (BAHA). These syntheses consist of 13 steps from the phenylpropanone 5.
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  • Naoko IWANAMI, Yuichi HASHIMOTO, Koichi SHUDO
    1996 Volume 44 Issue 5 Pages 919-926
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Two homopurine sequences of meso-DNAs (DNAs having an alternating sequence of 2-deoxy-L-ribose and 2-deoxy-D-ribose in their suger moieties), d(LADG)5 and d(LGDA)5, were prepared. Both d(LADG)5 and d(LGDA)5 interacted with the corresponding complementary natural DNAs, d(DCDT)5 and d(DTDC)5, respectively. In the interactions, pH-dependent duplex/triplex selectivity was observed, i.e., meso-d(Pu)10 formed a duplex at pH 7.5 and a triplex at pH 5.0 with the complementary D-d(Py)10. The meso-d(Pu)10/D-d(Py)<10> complex showed a CD spectrum similar in shape to that of the natural complex, suggesting that meso/natural complexes form right-handed helices. At pH 7.5, ethidium bromide intercalated into both d(LADG)5/d(DCDT)5 and d(LGDA)5/d(DTDC)5 duplexes. A clear difference between d(LADG)5/d(DCDT)5 and d(LGDA)5/d(DTDC)5 was observed at pH 5.0. Addition of ethidium bromide did not affect the formed d(LADG)5/d(DCDT)5 triplex, and ethidium bromide did not interacalate into the triplex. On the other hand, d(LGDA)5 did not form a triplex with d(DTDC)5 in the presence of ethidium bromide even at pH 5.0, but it formed a duplex. Ethidium bromide intercalated into the duplex at pH 5.0.
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  • Katsuo SHINOZAKI, Kazuhiro MIZUNO, Yukio MASAKI
    1996 Volume 44 Issue 5 Pages 927-932
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    D-erythro-Sphingosine (1) was synthesized from D-glucosamine (2) as a chiral pool through stereoinversion of the C(3)-hydroxyl group via an oxidation-reduction sequence, transformation to the erythro-amino-alcohol chiron (9) protected as the oxazolidinone, and elongation of the side chain at the C(6)-position of the derived chloride (12).
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  • Satoru NAGAMURA, Yutaka KANDA, Akira ASAI, Eiji KOBAYASHI, Katsushige ...
    1996 Volume 44 Issue 5 Pages 933-939
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    We found that treatment of the 8-O-protected-3-hydroxy derivatives of duocarmycin B2 (DUMB2, 1c) with camphorsulfonic acid (CSA) in toluene interestingly gave A-ring pyrrole analogs of DUMB2 (1c) in good yields. Their structures were unambiguously elucidated on the basis of NMR and mass spectrometry, and the mechanism was considered to be a Wagner-Meerwein type rearrangement. On the other hand, treatment of the 9-O-protected-3-hydroxy derivatives of duocarmycin B1 (1b) with CSA afforded different rearrangement products. In the case of bulky groups at the 9-O position, such as a tert-butyldimethylsilyl group, normal A-ring pyrrole analogs were obtained. Under the same condition, however, the 9-O-N, N-dimethylcarbamoyl-3-hydroxy compound of 1b gave a spiro compound, which was derived from a 1, 2-shift of the methoxycarbonyl group and a bonding between the C-8 position and the C-2' position. Compounds having a protective group of medium size gave a mixture of the normal rearrangement and the spiro derivative.
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  • Yoshiji TAKEMOTO, Jun TAKEUCHI, Ken-ichiro MORIO, Takahisa NAKAMOTO, C ...
    1996 Volume 44 Issue 5 Pages 940-947
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    A nucleophilic addition of alkyllithiums to the (Z)-dienone iron-tricarbonyl [Fe(CO)3] complex (3) gave the (Z)-dienol complex (4) exclusively, while the reaction of 3 with alkylmagnesium bromide or trialkylaluminum provided the (E)-dienol complex (2) via the isomerization of 3 to the (E)-dienone complex (1). Application of this methodology was demonstrated in a formal synthesis of both (+)- and (-)-frontalin from the same chiral starting material, {(2S, 5S)-(2E, 4Z)-tricarbonyl[2-5-η-11-chloro-2, 4-undecadien-6-one]iron} (8).
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  • Yoshiji TAKEMOTO, Jun TAKEUCHI, Eiki MATSUI, Chuzo IWATA
    1996 Volume 44 Issue 5 Pages 948-955
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    A 1-iminobutadiene-iron tricarbonyl [Fe(CO)3] complex (1) reacts with various organometallic nucleophiles in a stereoselective manner, and especially, by use of organocerium reagents, only single secondary amine complexes (2) were obtained in good yields. Application of this methodology was demonstrated in the asymmetric synthesis of hydroxyethylidene dipeptide isostere from the chiral starting material N-{(2R)-(2E)-tricarbonyl[2-5-η-2, 4-pentadienylidene]iron} benzylamine (1b).
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  • Toshiaki SAITOH, Taichi OYAMA, Kiyomi SAKURAI, Yosihiro NIIMURA, Mitsu ...
    1996 Volume 44 Issue 5 Pages 956-966
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    The thermal addition reaction of various aroylketenes (C) generated by the thermolysis of 5-aryldioxofurans (A) to 1-aryl-1-trimethylsilyloxyethylenes gave 1, 5-diarylpentane-1, 3, 5-triones (D) and 2, 6-diaryl-4H-pyran-4-ones (E). The introduction of electron withdrawing substituents in the aroylketene and of electron donating substituents facilitated the addition reaction. The observed substituent effects and the reaction mechanism are interpreted in terms of molecular orbital analyses.
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  • Taisuke ITAYA, Kazuo OGAWA, Yasutaka TAKADA, Tozo FUJII
    1996 Volume 44 Issue 5 Pages 967-971
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Oxidations of N6-methyladenine (8a) and N6-benzyladenine (8b) with m-chloroperoxybenzoic acid (MCPBA) in methanol have been found to afford the N(1)-oxides 7a, b in 36% and 35% yields, respectively. The structure of 7b has been established by leading it to N6-methoxyadenine (10) through O-methylation, Dimroth rearrangement, and nonreductive debenzylation. On the other hand, N6, N6-dimethyladenine (16) afforded the N(3)-oxide 17 in 40% yield on treatment with MCPBA in methanol. On the basis of these findings, together with data accumulated for N-oxidations of adenine, Nx-monosubstituted adenines, and 6-substituted purines, the formation of hydrogen bonding between the 6-amino NH and the carbonyl oxygen of a peroxycarboxylic acid may account for regioselective N(1)- and N(7)-oxidations of adenine and Nx-monosubstituted adenines.
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  • Tadashige CHIBA, Toshifumi AKIZAWA, Motomi MATSUKAWA, Masatoshi NISHI, ...
    1996 Volume 44 Issue 5 Pages 972-979
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    In order to confirm the structures of spidamine and joramine, identified from the venom of a spider (Nephila clavata), we convergently synthesized both compounds, which have a common side chain of N-(L-asparaginyl)-N'-(3-aminopropyl-β-alanyl)-1, 5-pentanediamine. A synthon of the common side chain was synthesized by starting with n-propanolamine which was converted to 7-azido-N-benzyloxycarbonyl-4-azaheptanoic acid N-hydroxysuccinimidyl ester. The ester was coupled with tert-butyloxycarbonyl-L-asparaginyl-1, 5-pentanediamine to give the synthon of the common side chain. In the final synthesis of spidamine, the synthon of the common side chain was reacted with 2, 4-dibenzyloxyphenylacetic acid N-hydroxysuccinimidyl ester, obtained by Willgerodt-Kindler reaction of 2, 4-dihydroxyacetophenone. The protected spidamine was catalytically hydrogenated to remove protective groups, affording spidamine itself in 13% yield from n-propanolamine. In the final synthesis of joramine, the synthon of the common side chain was reacted with 4-benzyloxyphenyl acetic acid N-hydroxysuccinimidyl ester. The protected joramine was also catalytically hydrogenated to produce joramine itself in 11% yield.The conformations of both synthesized compounds were analyzed by 1H-NMR and 13C-NMR. Their blocking activities on glutamate receptors were examined using labster neuromuscular synapses.
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  • Florence ROHET, Catherine RUBAT, Pascal COUDERT, Eliane ALBUISSON, Jac ...
    1996 Volume 44 Issue 5 Pages 980-986
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    A series of 4, 6-diaryl pyridazinones, chemically related to trazodone, was synthesized and evaluated for analgesic activity. With ED50 values ranging from 8.4 to 46.7 mg kg-1 i.p. in the phenylbenzoquinone-induced writhing test (PBQ test), most compounds were several times more potent than acetaminophen (ED50=231.3 mg kg-1 i.p.) and noramidopyrine (ED50=68.5 mg kg-1 i.p.). A multiple linear regression analysis demonstrated a correlation between antinociceptive activity and lipophilicity, as well as electronic and steric factors. The most active pyridazinones 2c and 2j exhibited minimal sedative and neurotoxic effects at the dose of 25 mg kg-1 i.p. They were devoid of activity in the hot plate test and their analgesic activity was not significantly reversed by naloxone in the PBQ test. The antinociceptive response induced by morphine (0.15 mg kg-1 s.c.) in the PBQ test was greatly potentiated by 2c and 2j administered at the low doses of 1 and 2.5 mg kg-1 i.p., respectively. On the other hand, their analgesic effects were enhanced synergistically by 5-hydroxytryptophan combined with carbidopa. All these data imply that a significant part of the antinociceptive effect induced by 2c and 2j may involve both opioid and serotenergic pathways. In addition, these two pyridazinones did not exhibit any antidepressant properties in the forced swimming test, nor did they potentiate yohimbine-induced toxicity.
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  • Masahiro FUJITA, Hiroshi EGAWA, Teruyuki MIYAMOTO, Junji NAKANO, Jun-i ...
    1996 Volume 44 Issue 5 Pages 987-990
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    4-Substituted 6-cyclopropyl-6, 9-dihydro-5-methoxy-9-oxo-1H-imidazo[4, 5-f]quinoline-8-carboxylic acids (6) and 8-substituted 1, 5, 6, 11-tetrahydro-5-methyl-1-oxo-imidazo[4, 5-g]pyrido[1, 2, 3-de][1, 4]benzoxazine-2-carboxylic acids (7) were prepared as potential antibacterial quinolone derivatives. The appendages at C-4 of -6 and at C-8 of -7 were selected from 1-piperazinyl, 4-methylpiperazinyl, 3-aminopyrrolidinyl, and 3-aminomethylpyrrolidinyl groups. The 5-methoxyimidazoquinolones 6 were superior to the corresponding ofloxacin type analogues 7 in in vitro antibacterial activity. The activity of 6 was equipotent against S. aureus, but 2 to 16 times less potent against E. coli and P. aeruginosa compared to that of the 5-fluoro analogue 3.
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  • Mitsuaki OHTA, Takeshi SUZUKI, Tokuo KOIDE, Akira MATSUHISA, Toshio FU ...
    1996 Volume 44 Issue 5 Pages 991-999
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    We prepared a novel series of conformationally restricted fused imidazole derivatives 4b, 4c and 4d (possessing 4, 5, 6, 7-tetrahydroimidazo[4, 5-c]pyridine and substituted 4, 5, 6, 7-tetrahydro-1H-benzimidazole for 4b, 5, 6, 7, 8-tetrahydroimidazo[1, 2-a]pyridine for 4c and 5, 6, 7, 8-tetrahydroimidazo[1, 5-a]pyridine for 4d as a basic amine part and (2-methoxyphenyl)aminocarbonyl group as an aromatic-carbonyl part). Their activities were then evaluated as an 5-hydroxytryptamine (5-HT3) receptor antagonist which may be useful for the treatment of irritable bowel syndrome (IBS) as well as for nausea and vomiting associated with cancer chemotherapy. The most potent compound was N-(2-methoxyphenyl)-4, 5, 6, 7-tetrahydro-1H-benzimidazole-5-carboxamide 14 in this series with an ID50 value of 0.32 μg/kg on the von Benzold-Jarisch reflex in rats and an IC50 value of 0.43 μM on the isolated colonic contraction in guinea pig, approximately ten and two times more potent than ondansetron 1, respectively. The structure-activity relationships (SAR) study suggested that the high potency of 14 may be attributed to the suitable position and direction of the N-C-N centroid in the conformationally restricted imidazole ring against the planar (2-methoxy-phenyl)aminocarbonyl part in the binding of 14 to the receptor.
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  • Mitsuaki OHTA, Takeshi SUZUKI, Junya OHMORI, Tokuo KOIDE, Akira MATSUH ...
    1996 Volume 44 Issue 5 Pages 1000-1008
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    A novel series of 4, 5, 6, 7-tetrahydro-1H-benzimidazole derivatives 4, 5, 6 and 7 was prepared and evaluated for activities as 5-hydroxytryptamine (5-HT3) receptor antagonists which may be useful for the treatment of irritable bowel syndrome (IBS) as well as nausea and vomiting associated with cancer chemotherapy. These compounds were designed by modifying the aromatic-carbonyl part of N-(2-methoxyphenyl)-4, 5, 6, 7-tetrahydro-1H-5-benzimidazolylcarboxamide 3, leaving the imidazole moiety unchanged as the amine part. The indole derivatives 7d, g, h and indolizine derivatives 7k, l were found to be highly potent on the von Bezold-Jarisch (B.J.) reflex test with ID50 values of below 0.1 μg/kg, and the indoline derivative 6c, indole derivatives 7a, d, g, benzofurane derivative 7j and indolizine derivative 7k were observed to be very potent on the colonic contraction with IC50 values of below 0.1 μM. In particular, 7l was the most potent on the B.J. reflex (ID50=0.018 μg/kg), approximately 200 and 50 times more potent than ondansetron 1 and granisetron 2, and 7k was the most potent on the colonic contraction (IC50=0.011 μM), approximately 70 and 6 times more potent than 1 and 2, respectively.
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  • Takashi SAWADA, Katsuya FUKUMARU, Hiromu SAKURAI
    1996 Volume 44 Issue 5 Pages 1009-1016
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    ESR is useful for determining the unpaired electronic state around paramagnetic metal ions such as, copper(II), iron(III) and manganese(II). The coordination structure of Cu(II) complexes was examined by ESR. ESR spectra were measured for a series of polyamine Cu(II) complexes, whose coordination modes are square-planar, axially-coordinate square-planar, tetrahedral and distored square-planar (copper ion displaced from N4 plane). ESR parameters, g-values and hyperfine coupling constants, A-values, were found to be correlated with the coordination mode of the complex, in which g vs. A plots gave important information on coordination structure of the complex. Moreover, linear relationships between ESR parameters and stability constants or halfwave potentials of the Cu(II) complexes were observed. Based on these results, the coordination structure around the Cu(II) in copper complexes as well as copper proteins was predicted by ESR spectra and associated parameters.
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  • Guoning QIU, Hidenao TOYODA, Toshihiko TOIDA, Ichiro KOSHIISHI, Toshio ...
    1996 Volume 44 Issue 5 Pages 1017-1020
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    An ion-exchange high-performance liquid chromatography procedure was developed for analysis of mixtures of N-acetyldermosine, N-acetylchondrosine and N-acetylhyalobiuronic acid produced quantitatively by heating dermatan sulfate, chondroitin sulfate and hyaluronan in dimethyl sulfoxide (DMSO) containing 0.1% (v/v) H2O at 80°C for 48 h. These disaccharides were eluted from a TSK gel SAX column using 0.1 M acetic acid containing KCl, and detected fluorometrically by post column derivatization. The eluate was mixed with 2-cyanoacetamide solution and alkaline solution, and heated at 110°C for 4 min. The resultant compounds were detected fluorometrically (Ex. 335 nm and Em. 390 nm). The usefulness and practicality of the present method were verified by applications to the determination of glycosaminoglycans in tissues.
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  • Yuji YAMAUCHI, Hatsuo MAEDA, Hidenobu OHMORI
    1996 Volume 44 Issue 5 Pages 1021-1025
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Application of the well-known electrocatalytic oxidation of alcohols by 2, 2, 6, 6-tetramethylpiperidinyl-1-oxy (TEMPO) as a novel tool for the amperometric detection of alcohols under basic conditions has been examined. Cyclic voltammograms of TEMPO in the absence and the presence of 1-pentanol, diethyleneglycol, and glucose demonstrated that these alcohols can electrochemically detected in terms of the anodic response of an aqueous 150 mM NaOH solution of TEMPO at a glassy carbon electrode. In flow injection analysis (FIA) utilizing an aqueous 150 mM NaOH solution of 100 μM TEMPO as a carrier solution with an applied potential of 0.4 V vs. saturated calomel electrode (SCE) and a flow rate of 0.5 ml/min, a good dependency of FIA responses upon the concentration was observed for 1-pentanol (20 μM-1 mM), diethyleneglycol (5 μM-1 mM), and glucose (5 μM-1 mM). Reproducible and stable responses have been obtained for these alcohols on repetitive injections of the sample solutions. The results on the FIAs of various alcohols have demonstrated that the amperometric detection of primary alchols and especially polyhydroxylated compounds such as 1, ω-diols and carbohydrates can be achieved with a high sensitivity by the present methodology.
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  • Hiroshi MORITA, Shinji NAGASHIMA, Yuki UCHIUMI, Osamu KUROKI, Koichi T ...
    1996 Volume 44 Issue 5 Pages 1026-1032
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Antitumor activities on Sarcoma 180A of a series of cyclic pentapeptides, astins, isolated from the roots of Aster tataricus, were examined. The activities on various congeners of the dichlorinated proline residues prepared by chemical conversion and a hepatic microsomal biotransformation in rats suggested that 1, 2-cis dichlorinated proline residues of astins A, B and C play an important role in the antitumor activity of astins.
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  • Hiroyuki FUCHINO, Soh KONISHI, Tetsuya SATOH, Akiko YAGI, Kohei SAITSU ...
    1996 Volume 44 Issue 5 Pages 1033-1038
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    The constituents of Betula platyphylla var. japonica were identified as follows : Fresh leaves : 12-O-acetyl-3-O-malonylbetulafolienetriol, 12-O-acetyl-3-O-malonylbetulafolienetriol oxide I (=papyriferic acid), 12-O-acetyl-betulafolienediolone, hydroxyhopanone, caryophyllene oxide, kaempferol 3-O-(4-O-acetyl)-α-L-rhamnopyran-oside, quercetin 3-O-(4-O-acetyl)-α-L-rhamnopyranoside. Outer bark : betulin, lupeol, betulinic acid, betulone, betulin 3-O-caffeate, oleanolic acid, oleanolic acid 3-O-acetate. Inner bark : (-)-catechin, (-)-catechin 7-O-β-D-xylopyranoside, rhododendrin (=betuloside), aceroside VII, aceroside VIII, 1, 7-bis[4-hydroxyphenyl]-3-hepten-5-one, 2-hydroxy-1, 7-bis[4-hydroxyphenyl]-3-hepten-5-one, acerogenin E, (3R)-3, 5'-dihydroxy-4'-methoxy-3', 4"-oxo-1, 7-diphenyl-1-heptene, 7α-hydroxy-β-sitosterol, 7β-hydroxy-β-sitosterol. Root bark : dammarenediol II 3-O-p-coumarate, dammarenediol II 3-O-caffeate, ocotillol II 3-O-caffeate, stigmast-4-ene-3-one. Spikes : caryo-phyllene oxide, (-)-rhododendrol (=betuligenol), 12-O-acetylbetulafolienetriol. The compounds with an asterisk are new.
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  • Suwannee P. PANOMSUK, Tomomi HATANAKA, Tetsuya AIBA, Kazunori KATAYAMA ...
    1996 Volume 44 Issue 5 Pages 1039-1042
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    The swelling properties of hydrophilic cellulose matrices were studied using three drugs having different water solubility : indomethacin, theophylline, and mannitol. Two swelling parameters : maximum swelling index (V) and the apparent diffusion coefficient of water in the matrix (Dw), were calculated from the swelling data and were used to describe structures and properties of the swollen matrices. The V value indicates the swelling extent as well as the capacity of maintaining the matrix shape, whereas Dw represents the swelling rate that also reflects the structural resistance of the polymer network against the movement of water molecules. The results show that both polymers and incorporated drugs influence the swelling properties of the matrices. Polymers that contain more hydroxypropoxyl group produce matrices with high integrity, even in the presence of drugs. V values indicated that the capacity of the matrices to maintain their shape depends on polymer (i.e., the swelling part). The effect of drug solubility can be seen from Dw values. For a highly water-soluble drug, the structural resistance of the swollen matrices is mainly governed by the drug. In contrast, this primarily influenced by the polymer in the case of drugs that are slightly or poorly water soluble.
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  • Yorinobu YONEZAWA, Shuichi KAWASE, Yuji JINDE, Hisakazu SUNADA
    1996 Volume 44 Issue 5 Pages 1043-1048
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Effect of tablet shape on dissolution was examined as an example of the application of the z-law and Ln-z equations. The tablet shape can be altered systematically by changing the diameter and weight of tablet, since these equations were applicable for dissolutions with various optional initial amounts within the amount required to saturate the solution.It was confirmed that the z-law and Ln-z equations efficiently treated the dissolution of tablet irrespective of the weight and size, i.e., the diameter and thickness as well as crystalline particles. Both dissolution equations gave almost the same dissolution rate constants for a tablet of a fixed weight and size.The dissolution rate constant changed with the tablet weight and size, and it was suggested that the latter factor probably had greater effect. The tablet size was then converted to the degree of isometricity or shape factor. Then, the effect of shape on the dissolution rate constants of tablets (kz) was estimated using the z-law equation. The kz-value of a long cylindrical tablet was large, and it decreased to reach a minimum value with decrease in tablet thickness and increase in diameter. The kz-value increased to reach almost a fixed value of shallow cylindrical tablets as if it had been obtained by a rotating disk method.The difference in the dissolution rate constants was examined using a specially devised tablet of which the flat-faced surface or curved surface was coated with wax. Dissolutions with these tablets suggested that the dissolution rate constant of the long cylindrical tablet was the larger of the two. Also, the way in which the flat-faced and curved surfaces contribute to the kz-value was examined as a function of the ratio of flat-faced surface area (2Sd) to the whole surface area (So), i.e., 2Sd/So. The kz-value decreased almost straightly within the 2Sd/So-value reached to around 0.63, showing a close similar value where the 2Sd/So-value was larger than around 0.73. Thus, it was suggested that the tablet form should be taken into consideration when necessary.
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  • Isamu MIYATA, Hiroshi MIYAMOTO, Masakatsu YONESE
    1996 Volume 44 Issue 5 Pages 1049-1055
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    To elucidate the effects of chain lengths of alcohols (1-butanol, 1-hexanol, and 1-octanol) as cosurfactants on the formation of a single-phase microemulsion (L-region) in n-heptane/n-alcohol/sodium dodecyl sulfate (SDS)/water systems, the phase diagrams of pseudoternary systems were determined under a fixed SDS/alcohol weight ratio (=0.5). Conductivity, viscosity and light scattering intensity of the L-region were measured at 30°C, and the results discussed from the microstructure of these systems. Using the SDS-free model system, the distribution of alcohol and the interfacial tension between oil (heptane) and water phases were measured in the presence of alcohol. The difference in distribution of alcohols resulting from differences in the chain lengths was found to be one of the key factors determining the extensions of the region of microemulsion and the microstructures. The L-regions in the hexanol and octanol systems were much smaller than in the butanol system. The continuous phases of these systems were the oil-rich medium (water-in-oil-type) throughout the L-region with increasing the water content. The L-region in the butanol system, on the other hand, was larger and the condtinuous phases of this system changed gradually from the oil-rich to the water-rich medium (oil-in-water-type) through the bicontinuous medium (bicontinuous-type) with increasing the water content.
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  • Toshio YAJIMA, Shigeru ITAI, Hidefumi HAYASHI, Kozo TAKAYAMA, Tsuneji ...
    1996 Volume 44 Issue 5 Pages 1056-1060
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Particles size distribution of granules for tablet compression manufactured by a high-shear-mixer were examined, and the relationship between this size distribution and physical properties (e.g., angle of repose, angle of spatula, loose bulk density, tapped bulk density, compressibility, hardness of tablets and weight variation of tablets) was determined. Optimization of particle size distribution was also carried out, taking the effects of hardness and weight variation into consideration.The particle size distribution of granules for tablet compression could be expressed as a function of median particle size and standard deviation with a logarithmic normal distribution. The physical properties of granules for tablet compression and tablets were significantly affected by this factor. A contour diagram of the hardness of the tablets compressed with an autograph was consistent with that of compressibility. The contour diagram of the hardness of tablets compressed with a rotary tableting machine was different, however, and was found to be affected by both the fluidity of granules for tablet compression and compression speed. Furthermore, tablet hardness increased as the median particle size decreased, when the standard deviation was less than 1.0.The physically properties of tablets could be predicted from the contour diagram of optimum particle size distribution of granules for tablet compression. As a result, the time spent making the tablet formulation could be reduced. It was found that the optimum ranges of median particle size and standard deviation were less than 150 μm and less than 1.0, respectively.
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  • Susana ROMERO, Aurora REILLO, Begona ESCALERA, Pilar BUSTAMANTE
    1996 Volume 44 Issue 5 Pages 1061-1064
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    The solubility of paracetamol was studied at 25°C in mixtures of amphiprotic and aprotic solvents of varying polarity (ethyl acetate-ethanol, ethanol-water, dioxane-water). A plot of the solubility mole fraction of the drug versus the solubility parameter of the solvent mixtures reached a peak in dioxane-water, and two solubility maxima within the polarity range provided by the ethanol-water and ethanol-ethyl acetate mixtures. This "chameleonic effect" can be quantitatively described in terms of cavity formation, nonspecific and specific interactions, represented by the Hildebrand solubility parameter and the acidic and basic solubility parameters of the solvent mixtures. The model predicts two solubility maxima, as found experimentally. The behavior of paracetamol in dioxane-water mixtures is similar to that of other drugs, showing a single maximum, although a small peak and a valley are also observed near the solubility parameter region where the maximum in ethanol-water appears. An increase in the temperature of fusion of the solid phase by about eight degrees was observed after equilibration of the powder with ethanol, ethyl acetate and dioxane. No changes in the solid phase were observed in water and aqueous mixtures below 50% water. The same change in the solid phase was also found in ethanol-ethyl acetate mixtures; it was independent of the nature and cosolvent ratio and had little effect on the relative variation of solubility with solvent composition. The solid phase contributes as a constant to the total solubility.
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  • Yukio ASO, Sumie YOSHIOKA, Shigeo KOJIMA
    1996 Volume 44 Issue 5 Pages 1065-1067
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    The crystallization rates of fused nifedipine in 6 mixtures with different polymeric pharmaceutical excipients were each measured as a function of the water content using an isothermal microcalorimeter. In all the excipients studied, the crystallization rate increased as the water content increased, but the extent of the increase in crystallization rate varied with the excipient. The spin-lattice relaxation rates (1/T1) of deuterium oxide absorbed by the mixtures suggested that water mobility differed according to the excipient even if water content of the mixtures was the same. The crystallization rate of mixtures with crystalline cellulose, methyl cellulose, cornstarch and polyvinyl alcohol correlated with the 1/T1 values. It is suggested that the difference in crystallization rate among the excipients can be explained by the water mobility which is governed by the interaction between water and excipient molecules. Increase in the mobility of water in the mixtures may decrease the nifedipine matrix viscoelasticity through the plasticizing effect of water, resulting in an increase in the crystallization rate. The plasticizing effect of water was confirmed by measuring nifedipine mobility in a sample without excipients. The nifedipine mobility, determined by measuring the spin-spin relaxation time of protons in fused nifedipine increased as the water content increased.
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  • Masahiro FUKAHORI, Yasuo TAKATSUJI, Hiroaki TAKAHASHI, Hiroshi SATO, T ...
    1996 Volume 44 Issue 5 Pages 1068-1073
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    The partition of p-hydroxybenzoic acid esters (parabens) between polyoxyethylene alkyl ether (PAE) micelles and an aqueous phase was studied by a solubility method and ultrafiltration. Paraben solubility in aqueous PAE solution and the extent of interaction between parabens at a low concentration and the micelles varied with the structure of PAEs. The binding capability for methyl, ethyl, propyl and butyl paraben per unit hydrocarbon of PAE molecules increased with oxyethylene chain length but decreased with an increase in hydrocarbon chain length. The interactions between parabens and PAEs thus appear to be influenced by the rigid or bulky character of the micelles, which is dependent on the structures of the surfactant micelles.The extent of the interaction is related to the hydrophile-lipophile balance of the surfactants reported by Davies, and to the carbon number in the alkyl group of parabens. We proposed an empirical formula to estimate the magnitude of the interaction, which was successfully applied not only to PAEs but also to ester-type non-ionic surfactants generally used in eye drops and syrups. In the case of aqueous based pharmaceuticals with various non-ionic surfactants, it is highly probable that the paraben concentration required for antibacterial effectiveness could be determined by the empirical formula.
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  • Toshihiko YOSHIDA, Yoichi YAMAMOTO, Hitomi ORITA, Masato KAKIUCHI, Yos ...
    1996 Volume 44 Issue 5 Pages 1074-1085
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    A series of 7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl-1, 4-dihydro-4-oxoquinoline-3-carboxylic acids bearing various substituents (H, F, Cl, Me, OH, OMe, OEt, OCH2F, OCHF2, OCF3, SMe) at the C-8 position was prepared and evaluated for in vitro antibacterial activity against both standard laboratory strains and bacteria resistant to quinolones such as ciprofloxacin (CPFX, 1) and ofloxacin (OFLX, 2) from clinical isolates. The 8-methyl (8a), 8-fluoro (9a), 8-chloro (10a) and 8-methoxy (12a) compounds were 4 times more potent than CPEX (1) against both gram-positive and gram-negative bacteria. But these four compounds caused injury to the chromosomes of mammalian cells at a concentration of 100 μg/ml. Next, a series of quinolones having various substituents (H, Cl, Me, NH2, NHMe, NMe2) at the C-5 position was prepared and evaluated for antibacterial activity and injurious effect on the chromosome. We found that the 5-amino-8-methyl compound (8d) showed strong antibacterial activity (in vitro antibacterial activity of 8d is 4 times more potent than that of CPFX (1) against both gram-positive and gram-negative bacteria), reduced injury to the chromosome, and reduced quinolone-type toxicity (free from both photoxicity at a dosage of 30 mg/kg in guinea pigs (i.v.) and convulsion-inducing activity when coadministered with fenbufen at a dosage of 100 mg/kg in mice (i.p.)).
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  • Seiji NAGUMO, Sumiko ISHIZAWA, Masahiro NAGAI, Takao INOUE
    1996 Volume 44 Issue 5 Pages 1086-1089
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    From a mixture of the bark and twigs of Acer nikoense MAXIM. (Aceraceae), nine compounds (1-9) were newly isolated. Compound 1 was identical with acerogenin E, and compounds 8 and 9 were β-orcinol derivatives. Acerogenin K (2), a new diarylheptanoid of the cyclic diphenyl type, yielded acerogenin E on oxidation. Acerogenins F (3) through L (7) are new diarylheptanoids of the cyclic biphenyl ether type, whose skeletons and substituents of the diphenyl ether moieties are the same as those of acerogenin A. Their structures were elucidated on the basis of chemical and spectroscopic evidence.
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  • Haruhiro FUJIMOTO, Miyuki INAGAKI, Yoko SATOH, Eiji YOSHIDA, Mikio YAM ...
    1996 Volume 44 Issue 5 Pages 1090-1092
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Two cyclopentabenzopyran-4-ones tentatively named CT-2 and -3 have been isolated as new monoamine oxidase (MAO)-inhibitory components from an Ascomycete, Coniochaeta tetraspora, together with a new chlorinated pigment tentatively named CT-1. The structures of CT-2 and -3 have been elucidated, and these products were shown to be identical with coniochaetones A and B, respectively, which have recently been isolated as antifungal components from Coniochaeta saccardoi. CT-1 appears to be a seco-anthraquinone.
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  • JaeHoon LEE, Soo-Muk CHO, Kyung-Sik SONG, Nam-Doo HONG, Ick-Dong YOO
    1996 Volume 44 Issue 5 Pages 1093-1095
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    The carbohydrate-peptide linkage in acidic heteroglycopeptide from Phellinus linteus was characterized. Amino acid analysis showed large amounts of serine and threonine. β-Elimination results in the reduction of serine and threonine and a subsequent increase in alanine after reduction. These results indicated the presence of O-type linkage in the polymer.
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  • Masami ISHIHARA, Atsunori SANO
    1996 Volume 44 Issue 5 Pages 1096-1098
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    The synthesis of optically active phosphatidylcholines (D- and L-4) containing two of the same fatty acid moieties in a molecule is described. Optically pure D-enantiomers (D-4) were obtained from 2, 3-di-O-acyl-sn-glycerol (D-1) in high yield by phosphorylation with phosphorus oxychloride and subsequent treatment with choline tosylate (11a). L-Enantiomers (L-4) were also prepared in a similar manner from 1, 2-di-O-acyl-sn-glycerol (L-1). The whole procedure is easy and useful for the synthesis of enantiomeric phosphatidylcholines.
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  • Hajime KATAYAMA, Osamu KATO, Kimiyoshi KANEKO
    1996 Volume 44 Issue 5 Pages 1099-1101
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    The reported structure of an indolo[1, 2-b]indazole derivative is revised to a indazolo[2, 3-a]quinazoline derivative based on detailed NMR analyses and chemical transformation.
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  • William GAFFIELD
    1996 Volume 44 Issue 5 Pages 1102-1103
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    The absolute configurations of the cis-dihydroquercetin-3-O-β-L-rhamnosides isoastilbin and neoisoastilbin are reaffirmed as 2R, 3S and 2S, 3R, respectively, despite recent reports to the contrary.
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  • Eiko TOYOTA, Chisako CHINEN, Haruo SEKIZAKI, Kunihiko ITOH, Kazutaka T ...
    1996 Volume 44 Issue 5 Pages 1104-1106
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Salicylaldehyde derivatives carrying an amidinium group react spontaneously with α-amino acids in copper-containing aqueous media to afford very stable Schiff base copper chelates. A variety of Schiff base chelates were prepared from various α-amino acids. Each α-amino acid provides enantiomeric isomers due to the asymmetric α-carbon, except for glycine. Inhibitory activity of these amidinium chelates toward trypsin was generally very strong. Thus these compounds represent a novel series of potent trypsin inhibitors. The structure-activity relationship of the inhibitors is discussed based on their inhibition constants, though the variations are not large.
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  • Masa KAKIUCHI, Yasuhiro IZUNO, Mitsuko MAEDA, Kaori UEDA, Kazuko FUJIW ...
    1996 Volume 44 Issue 5 Pages 1107-1110
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Fibrinogen-related peptides, monomeric cyclic peptides through a disulfide bond [cyclo(H-Cys-Arg-Gly-Asp-Phe-Cys-NH2), cyclo(H-Cys-Arg-Gly-Asp-Phe-Cys-Gly-NH2), cyclo(H-Cys-Arg-Gly-Asp-Cys-NH2) and cyclo(H-Cys-Arg-Gly-Asp-Cys-Gly-NH2)], were prepared by the solid phase method with disulfide bond formation on the solid support. The acetamidomethyl group was used for protection of the thiol group of Cys and synthetic peptide-resins were treated with iodine to give the disulfide bond. Monomeric cyclic peptides were obtained as main products. Purified S-acetamidomethylated peptides were also oxidized with iodine, but the desired materials could not be isolated by HPLC. The disulfide formation from S-acetamidomethylcystein-containing peptide resin by iodine treatment on the solid support was more effective than that from S-acetamidomethylcysteine-containing peptide. The inhibitory effects of the cyclic peptides on platelet aggregation were much more potent than that of H-Arg-Gly-Asp-NH2.
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  • Yasumaru HATANAKA, Makoto HASHIMOTO, Kazuya I.-P. Jwa HIDARI, Yutaka S ...
    1996 Volume 44 Issue 5 Pages 1111-1114
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    A new biotinylated lactose derivative bearing a nitro-substituted chromogenic diazirine was synthesized. The biotinyl group within the structure enabled the performance of a convenient assay of GM3 synthase based on avidin-biotin technology, and the Km values of this biotinylated photoprobe were determined as 40 and 47 μM using bovine brain and rat liver Golgi as enzyme sourced, respectively. Furthermore, the sialylation of lactosylceramide, a natural acceptor substrate for GM3 synthase, was completitively inhibited by this synthetic analog. The reagent could be a useful chromogenic photoprobe for GM3 synthase.
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  • Yutaka ASAHI, Masami TANAKA, Naohiro YAMAMOTO
    1996 Volume 44 Issue 5 Pages 1115-1118
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Triamterene, 6-phenyl-2, 4, 7-triaminopteridine (1), a diuretic, gave two steps of two-electron reduction waves on Tast polarography (TP). The first step was ascribed to the reversible reduction of 1 into unreducible 5, 8-dihydrotriamterene (2) by cyclic voltammetry (CV). Tautomerization of 2 to reducible 7, 8-dihydrotriamterene (3) was rapid first-order reaction catalyzed by acid and base. The second step was attributed to the irreversible reduction of 3 into 5, 6, 7, 8-tetrahydrotriamterene (4), which was oxidized to 2, 4-diamino-6-phenylpteridine at a more positive potential than those of 2 and 3 into 1 on CV. The oxidation of 3 to 1 was observed at a more positive potential than that of 2 to 1 on CV. The anodic wave of 1 on TP in alkaline solution was ascribed to formation of the mercury complex of 1.
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  • Rui-Hua TIAN, Emi OHMURA, Hitoshi YOSHIMITSU, Toshihiro NOHARA, Masaha ...
    1996 Volume 44 Issue 5 Pages 1119-1121
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    From the roots of Solanum abutiloides, glycosides of 26-hydroxy- and 26-aminocholestane were obtained and their structures were characterized. Both of them were regarded as key intermediates in the biogenesis of steroidal alkaloids.
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  • Noriko MATSUDA, Hiromi SATO, Yasunori YAOITA, Masao KIKUCHI
    1996 Volume 44 Issue 5 Pages 1122-1123
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    Two neolignan glycosides, dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranosides with the enantiometric aglycones (1 and 2), have been isolated from the leaves of Viburnum awabuki K. KOCH. These structures were identified by spectroscopic evidence and the absolute configurations of these compounds were elucidated on the basis of circular dichroism data.
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  • Noriyasu FUKUOKA, Toyohisa TSUKAMOTO, Misao NAKANO, Akira SHIBATA, Tak ...
    1996 Volume 44 Issue 5 Pages 1124-1127
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    We analyzed the permeability of low-molecular weight drugs through the lipid bilayer membrane using a new model. This model (model 3) was compared with two conventional models (models 1 and 2) in the permeation behavior of cytosine arabinoside (ara-C) through mixed cholesterol-phosphatidylcholine liposomes using a dialysis bag.In models 1 and 2 the ara-C permeation rate is calculated based on the following premise : 1) The rate is proportional to the first degree of the difference between the equilibrium concentration in the external medium of the dialysis bag at time t=∞ and the concentration at each time.2) The rate is proportional to the first degree of the concentration difference between the inside and outside of the liposomes.Analysis using model 3 was performed on the premise that the ara-C permeation rate is proportional to the first degree of the concentration difference between the inside and outside of the liposomes and that between the inside and outside of the dialysis bag.The ara-C permeation coefficients through the liposomal membrane obtained using models 1, 2, and 3 were 2.9×10-5, 1.7×10-6, and 1.7×10-9 (cm/min), respectively. The models were evaluated according to Akaike's information criteria (AIC) and the sum of squares (SS). The best results were obtained using model 3 (AIC=-29.7, SS=1.2×10-1). These results suggest that the film resistance inside the dialysis bag should be considered one of the rate determining steps of drug permeation in an experimental system in which the outside but not the inside of the dialysis bag is agitated.
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  • Toshihiko YOSHIDA, Makoto TAKESHITA, Hitomi ORITA, Noriyuki KADO, Shin ...
    1996 Volume 44 Issue 5 Pages 1128-1131
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    (3S, 4S)-3-(tert-Butoxycarbonyl)amino-4-methylpyrrolidine (12a) was synthesized from L-aspartic acid (4) on a large scale. Methylation of dimethyl (2S)-N-benzyl-N-(9-phenylfluoren-9-yl)aspartate (5), easily derived from 4, with methyl iodide gave (3R)-3-methylaspartate (6a) in 91% yield with high diastereoselectivity. Reduction of 6a with lithium aluminum hydride, followed by hydrogenolysis, protection with di-tert-butyl dicarbonate, and mesylation gave 10a in 89% overall yield. Subsequently, reaction of 10a with benzylamine under a nitrogen atmosphere at room temperature, followed by hydrogenolysis, gave the target compound (12a) in 65% overall yield. In a similar manner to that described for the preparation of 12a from 5, compound 5 was converted into 4-ethyl and 4-propyl derivatives (12b, c) in 34% and 38% overall yields.
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  • Tatsuhisa KATO, Mamiko TEJIMA, Hirosato EBIIKE, Kazuo ACHIWA
    1996 Volume 44 Issue 5 Pages 1132-1134
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    The asymmetric synthesis of the (S)-(+)- and (R)-(-)-NZ-105 from the prochiral compound (1) was realized by using the modified Hunsdiecker reaction followed by the modified Michaelis-Arbuzov reaction with zerovalent palladium.
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  • Aya TANATANI, Hiroyuki KAGECHIKA, Isao AZUMAYA, Kentaro YAMAGUCHI, Koi ...
    1996 Volume 44 Issue 5 Pages 1135-1137
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    N, N'-Dimethyl-N, N'-diphenylguanidine (2a) and the corresponding guanidinium salt (2b) have crystal structures in which two phenyl groups are located face-to-face. Similar (cis, cis) conformations were also observed in various solvents. These structures may be useful as key building blocks to construct water-soluble aromatic layered molecules.
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  • Yasuyuki ENDO, Mitsuhiro YAMAGUCHI, Masaaki HIRANO, Koichi SHUDO
    1996 Volume 44 Issue 5 Pages 1138-1140
    Published: May 15, 1996
    Released on J-STAGE: March 31, 2008
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    (-)-Benzolactam-V8-310 reproduces the active conformation and biological activity of teleocidins. Various sizes and shapes of alkyl groups on aromatic nucleus of BL-V8 were synthesized as optically pure forms. Structure-activity results indicate that hydrophobic substituents at C-9 position plays a critical role for the appearance of biological activities.
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