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Juziro NISHIJO, Masako YASUDA, Mayumi NAGAI, Makiko SUGIURA
1994 Volume 42 Issue 4 Pages
761-767
Published: April 15, 1994
Released on J-STAGE: March 31, 2008
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The interaction of 8-anilino-1-naphtalenesulfonate (ANS) with heptakis(2, 3, 6-tri-O-methyl)-β-cyclodextrin (TOM-β-CD) was investigated in a 0.1 M phosphate buffer at pH 7.4 by fluorescence spectrophotometry. Utilizing the fact that the fluorescence intensity of ANS increases in the presence of TOM-β-CD, the thermodynamic parameters for inclusion complex formation were determined as follows : ΔG°=-8.95kJ·mol
-1 at 25°C, ΔH°=-10.9kJ·mol
-1, ΔS°=-6.3J·mol
-1·K
-1. The main driving force for the inclusion complex was considered to be the van der Waals-London dispersion forces, while the contributions of the hydrophobic interaction was small. Also, from the measurements of proton nuclear magnetic resonance spectra and studies with Corey Pauling Koltun models, the probable structure of the complex was determined. Further, the effects of permethylation on inclusion complex formation were discussed.
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Shin-ichi KONDO, Katsuyuki MURASE, Masayuki KUZUYA
1994 Volume 42 Issue 4 Pages
768-773
Published: April 15, 1994
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To provide the structural criteria for mechanically polymerizable vinyl monomers in metallic vessels, we carried out the MO calculations (AM1 method) of several acrylamide, acrylate and styrene derivatives as model compounds for such reactions. It was found that the nature of LUMO of vinyl monomers is closely related to the capability for initiation of mechanochemical polymerization. The following requisite concerning the nature of LUMO was shown to be a necessary condition for the activity of such reactions : Even if the LUMO energy is lower than 0.166eV in the AM1 scheme, the LUMO coefficient must be highly localized in the vinyl group. When the monomer does not meet this criterion, the introduction of a saturated group such as an alkyl group to insulate electronically the π-electron system of vinyl group from the rest of the molecules will lead to the mechanically polymerizable monomers.
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Yoko KANAZAWA, Seiko KUROGI, Shunji SHINOHARA, Yoko NODA, Kouji MASUDA
1994 Volume 42 Issue 4 Pages
774-778
Published: April 15, 1994
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The suppression of α-fluoro-β-alanine (FBAL) formation from 5-fluorouracil (FU) is an important subject in relation to tumor chemotherapy. This is the first comparative study of FU, 1-(2-tetrahydrofuryl)-5-fluorouracil(FT, a prodrug of FU) and of FT+uracil as a coadministration system (UFT) under an oral dose using the in vivo
19F NMR method. The slow release of FU from FT and the suppression of the catabolism of FU to FBAL in mouse livers and tumors by the coadministration of uracil with FT were demonstrated using consecutive NMR measurements. The applicability of the in vivo
19F NMR method to the drug evaluation in tumors and livers of small animals was successfully tested.
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Noriaki FUNASAKI, Sakae HADA, Saburo NEYA
1994 Volume 42 Issue 4 Pages
779-785
Published: April 15, 1994
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The self-association of penicillin G (PCG) and penicillin V (PCV) in 0.15 M potassium chloride solution has been investigated by frontal gel filtration chromatography (GFC) on Sephadex G-10 columns at 25°C. Analysis of the centroid volume, V
c, of a GFC profile yields the monomer concentration of a penicillin and the weight-average aggregation number, n
w. No critical micelle concentration is observed in the V
c vs. concentration profile for PCV. The n
w value for PCV is 2 at low concentrations and gradually increases with increasing concentration. PCG forms dimers only below 0.06 M, and provides useful GFC data for the investigation of dimerization. The dimerization constants of PCG and PCV are also evaluated from the concentration dependence of the derivative peak position at the trailing boundary. Stepwise aggregation constants, obtained from non-linear least-squares fitting of the centroid volume data, satisfactorily reproduce observed derivative chromatograms, and are used for calculations of the aggregate size distribution of PCV. The structure-association relationship and the effect of self-association on the bactericidal activity and chemical stability of the penicillins are discussed.
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Kunio HIROI, Kazushige HIRASAWA
1994 Volume 42 Issue 4 Pages
786-791
Published: April 15, 1994
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Palladium-catalyzed intramolecular metallo-ene reactions were studied using allylic sulfones as enophiles. Palladium-catalyzed reactions of allylic acetates and methyl carbonates bearing allylic sulfones at appropriate sites were carried out in acetic acid at 80°C to give cyclized products, cyclohexane derivatives, with extremely high diastereoselectivity. The stereochemistry of these reactions was examined under various reaction conditions using several model compounds.
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Koichi KAWASAKI, Tomohiro MURAKAMI, Kazuyoshi KOSHINO, Machiko NAMIKAW ...
1994 Volume 42 Issue 4 Pages
792-795
Published: April 15, 1994
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β-Cyclododecyl aspartate was prepared and its application to peptide synthesis was examined. Derivatives of β-cyclododecyl aspartate are more likely to crystallize and should be useful for peptide synthesis. The cyclododecyl ester was much stable to bases than the benzyl ester and rather more stable than the cyclohexyl ester. It was removable by HF treatment and trifluoromethanesulfonic acid treatment. β-Cyclododecyl aspartate was used for synthesis of laminin- and fibronectin-related peptides by solid phase and liquid phase methods.
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Yasuo TAKEUCHI, Yoshio KAMADA, Koji NISHIMURA, Hiromi NISHIOKA, Masayo ...
1994 Volume 42 Issue 4 Pages
796-801
Published: April 15, 1994
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As part of a series of studies on synthesis of chiral 1-alkyltetrahydroisoquinolines, asymmetric synthesis of 1-alkoxycarbonylmethyl-1, 2, 3, 4-tetrahydroisoquinolie (IV) was investigated. Two synthetic approaches using intermolecular and intramolecular Reformatsky-type reactions from (3R, 10bS)-3-phenyl-2, 3, 5, 6-tetrahydro-10bH-oxazolo[2, 3-a]isoquinoline (1) were attempted, but high stereoselectivity could not be obtained. For the purpose of determining the absolute structures of the compounds (2, 3) obtained by the Reformatsky-type reactions, transformation of 3a to a chiral 1, 3, 4, 6, 7, 11b-hexahydro-2H-benzo[a]quinolizine (14) was investigated.
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Masumi TAKEMOTO, Kazuo ACHIWA
1994 Volume 42 Issue 4 Pages
802-805
Published: April 15, 1994
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We have synthesized optically active α-phenylpyridylmethanols by using free baker's yeast (FBY) in water, immobilized baker's yeast (IMBY) in water, and IMBY in hexane.
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Magoichi SAKO, Reiko TOTANI, Kosaku HIROTA, Yoshifumi MAKI
1994 Volume 42 Issue 4 Pages
806-810
Published: April 15, 1994
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5, 6, 7, 8-Tetrahydro-5-deaza-5-thiapterins, (1a, 1d, and 1e), were conveniently synthesized by the thermal condensation of 5-bromo-6-chloroisocytosine (5) with cysteamines (6a-c) via the aliphatic S-N type Smiles rearrangement in ethanolic pH 7.0 buffer solution.
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Tadashi KATAOKA, Yasuhiro OHE, Akira UMEDA, Tatsunori IWAMURA, Mitsuhi ...
1994 Volume 42 Issue 4 Pages
811-816
Published: April 15, 1994
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3, 6-Dihydro-2H-selenopyrans 2 with an electron-withdrawing group at the 2-position were prepared by the Diels-Alder reaction of butadienes with selenoaldehydes generated in situ from selenocyanates 1 and triethylamine. Oxidation of the dihydroselenopyrans 2 with 1.5 eq of m-chloroperbenzoic acid provided 2H-selenopyrans 9 and 3, 6-dihydro-2H-selenopyran-2-yl m-chlorobenzoates 10. The benzoates 10 were smoothly converted into the selenopyrans 9 using polyphosphoric acid trimethylsilyl ester. The selenopyrans 9 were methylated with methyl trifluoromethanesulfonate to give Se-methyl selenopyranium trifluoromethanesulfonates 12. Deprotonation of the selenonium salts 12 with sodium hydride or triethylamine generated the selenabenzene derivatives 13, but they were too unstable to be isolated. Therefore, we confirmed the generation of 13 by
1H- and
13C-NMR spectroscopy at -30°C.
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Masahiro KAJIWARA, Ken-ichiro HARA, Kazuhiko TAKATORI
1994 Volume 42 Issue 4 Pages
817-820
Published: April 15, 1994
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The biosynthetic origin of carbonyl oxygen of uroporphyrinogen III was investigated. A model experiment using methyl benzoate labeled with
13C and
18O revealed isotope shifts of 0.015 and 0.036 ppm, corresponding to alkoxy-
18O- and carbonyl-
18O-labeled carbonyl carbons, in the
13C-NMR spectrum. Doubly
18O-labeled methyl benzoate showed an isotope shift of 0.050 ppm, equal to the sum of the two singly
18O-labeled carbonyl carbons. Next, [1-
13C, 1, 1, 4-
18O
3]5-aminolevulinic acid (ALA) was fed to Arthrobacter hyalinus, and the resulting porphyrin was esterified with trimethyloxonium tetrafluoroborate to afford
13C- and
18O-labeled uroporphyrin III octamethyl ester. The
13C-NMR signals exhibited carbonyl carbon
18O-isotope shifts of 0.013, 0.036 and 0.051 ppm, close to those obtained in the model experiment. Thus, the carbonyl oxygens of uroporphyrinogen III ang its oxidized product uroporpyrin III originated from ALA. This result shows that the loss of
18O at the acetate carbonyls of the A-ring in vitamin B
12 does not occur before the formation of uroporphyrinogen III.
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Shunsaku OHTA, Tetsuya YAMAMOTO, Ikuo KAWASAKI, Masayuki YAMASHITA, Yu ...
1994 Volume 42 Issue 4 Pages
821-825
Published: April 15, 1994
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The 4-position of the 1-methyl-1H-imidazole ring was lithiated by treatment of the corresponding 4-bromo derivatives with tert-butyllithium. This procedure was applied to synthesis of the left-hand part of pyronaamidine (1), which is a biologically interesting marine alkaloid.
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Yasumaru HATANAKA, Makoto HASHIMOTO, Hitoshi NAKAYAMA, Yuichi KANAOKA
1994 Volume 42 Issue 4 Pages
826-831
Published: April 15, 1994
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3-Phenyl-3-trifluoromethyl-diazirine derivatives with nitro and alkoxy substituents on their aromatic ring have been synthesized as carbene precursors for chromogenic detection of photolabeled products. Photolysis of the diazirines in methanol or cyclohexane gave intermolecular O-H or C-H insertion products, respectively. Spectroscopic properties of the photoproducts are such that detection of photolabeled products may be performed in a spectral region where the absorption due to most biological macromolecules is negligible. A carbon-14 analog of the diazirine was also prepared for microscale detection of labeled products. These nitro-substituted aryl diazirines should be applicable to a wide range of photoaffinity labeling studies, from tracer experiments to preparative isolation of labeled products by HPLC with spectrophotometric detection.
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Yuusaku YOKOYAMA, Makio TAKAHASHI, Mitsuru TAKASHIMA, Yukari KOHNO, Hi ...
1994 Volume 42 Issue 4 Pages
832-838
Published: April 15, 1994
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Dehydrotryptophans (9) having various substituents on the indole ring were synthesized by vinylation of the corresponding indole derivatives (6) with N-acetyldehydroalanine methyl ester (7a) by the use of a stoichiometric amount of palladium salt in acetic acid (stoichiometric condition). Although vinylation of 4-, 5-, and 7-bromoindoles (6b, g, l, m) with 7a occurred chemoselectively at the C
3-position to give the corresponding bromodehydrotryptophans (9b, g, l, m) under the stoichiometric condition, the palladium-catalyzed vinylation of 4-bromoindoles (6b, i) occurred at the bromine-bearing carbon at the C
4-position [0.1 eq PdCl
2(PPh
3)
2 in Et
3N-dimethylformamide]. Vinylation of 3-bromoindoles (17a, b) with 7a, or ethoxycarbonyl-(7b) or tert-butoxycarbonyldehydroalanine methyl ester (7c) also gave the dehydrotryptophan (18a-d) in good yields under catalytic conditions. One of two possible regioisomers of the vinylated products was isolated in all cases, and the geometry was determined as Z based on the coupling constant of the ester carbonyl carbon and the olefinic proton in the
13C-NMR spectrum.
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Masayuki SATO, Satoshi SUNAMI, Yoshiaki SUGITA, Chikara KANEKO
1994 Volume 42 Issue 4 Pages
839-845
Published: April 15, 1994
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A novel enantioselective synthesis of 1, 3-dioxin-4-ones having a 2-hydroxylated alkyl group at the 6-position has been accomplished by chiral tartaric acid-derived acylborane-mediated aldol condensation of the silyl enol ether derived from 6-methyl-derivatives of 1, 3-dioxin-4-one with achiral aldehydes.
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Hideaki MURATAKE, Atsushi MIKAWA, Takako SEINO, Mitsutaka NATSUME
1994 Volume 42 Issue 4 Pages
846-853
Published: April 15, 1994
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Synthetic pathways leading to model compounds 25, 27, 33, 20d, 32b, 37, and 42 for the marine alkaloids, herbindoles and trikentrins (1b-i), are presented. p-Toluenesulfonic acid-mediated indole cyclization reactions, 19→20 and 38→39, assisted with thiols such as benzylthiol or thiophenol, are key steps for preparation of the compounds having the 1, 6, 7, 8-tetrahydrocyclopent[g]indole structure. Novel reactions of the phenylsulfone group in 20c and 20e with allyltrimethylsilane in the presence of dichloroethylaluminum as well as with trimethylaluminum, are explained in terms of participation of an intermediary reactive species 29.
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Preparation of Alkyl-Substituted Indoles in the Benzene Portion. Part 11. Total Synthesis of (6R, 8S)-Herbindole A, (6R, 8S)-Herbindole B, (6R, 8S)-Herbindole C, (6R, 8S)-cis-Trikentrin A, (6R, 8S)-cis-Trikentrin B, (6R, 8R)-trans-Trikentrin B, and (6R, 8R)-iso-trans-Trikentrin B. Determination of the Absolute Structures of Natural Herbindoles and Trikentrins
Hideaki MURATAKE, Atsushi MIKAWA, Takako SEINO, Mitsutaka NATSUME
1994 Volume 42 Issue 4 Pages
854-864
Published: April 15, 1994
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The key intermediate, (3R, 5S)-3, 5-dimethyl-1-cyclopentenylmethanol (13) for chiral syntheses of herbindoles and trikentrins, was prepared from the known Dields-Alder adduct 12. Employing pertinent methodologies developed in the previous model study (preceding paper), the title herbindoles 31, 34, and 38 as well as trikentrins 4, 6, 41, and 47 having (6R, 8S)- or (6R, 8R)-absolute configuration of the dimethyl groups on the 1, 6, 7, 8-tetrahydrocyclopent[g]indole moiety were synthesized starting from 13 by way of precursor compounds 24b, 27a, and 27b for the crucial indole cyclization reaction. The following results were also obtained. (i) The proposed chemical structures of three herbindoles were confirmed. (ii) The absolute structures of herbindole A and trans-trikentrin B were established to be 1 and 7 by directly comparing optical properties between synthetic materials and the natural products. (iii) The absolute structures of herbindole B (2) and herbindole C (3) were assumed by analogy with 1. (iv) The absolute structures of cis-trikentrin B (6) and iso-trans-trikentrin B (8) were estimated by a circular dichroism (CD) analysis study. (v) Our previous proposal for the absolute configuration of cis-trikentrin A (4) was further confirmed.
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Masayuki YOKOTA, Takashi YANAGISAWA, Kazuhiro KOSAKAI, Shuichi WAKABAY ...
1994 Volume 42 Issue 4 Pages
865-871
Published: April 15, 1994
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Several 3-substituted-2H-cyclohepta[b]furan-2-one derivatives were prepared and tested in vitro for positive inotropic character. Introduction of an isopropyl group at the 5-position of compound 8a caused an increase of PIC
50 (negative logarithm of the dosage which increases the contractile force by 50%) from 4.48 to 5.10. Among the 5-isopropyl-8-alkoxy compounds, the isopropoxy compound 12f had the most potent activity with a PIC
50 value of 5.99. Conversion of the ester group at the 3-position to a methylene group and of the alkoxy group at the 8-position to a substituted amino group caused a decrease in activity. The most active compound, 12f, was also found to have a weaker heart rate (HR)-increasing effect compared to milrinone and amrinone.
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Masaru KIDO, Koji HASHIMOTO
1994 Volume 42 Issue 4 Pages
872-876
Published: April 15, 1994
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The crystal structures of nadifloxacin [9-fluoro-6, 7-dihydro-8-(4-hydroxy-1-piperidyl)-5-methyl-1-oxo-1H, 5H-benzo[i, j]quinolizine-2-carboxylic acid, OPC-7251]anhydride and its hemihydrate were determined by X-ray analysis. In both crystals, two crystallographically independent molecules (A and B) are contained in an asymmetric unit. Two of molecule A and two of molecule B are tightly bound by hydrogen bonds around a center of symmetry. The structural features of nadifloxacin molecules in the two crystals are very similar to each other.
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Toshiya MORIE, Shiro KATO, Hiroshi HARADA, Naoyuki YOSHIDA, Jun-ichi M ...
1994 Volume 42 Issue 4 Pages
877-882
Published: April 15, 1994
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The enantiomers, (S)-(-)-1 and (R)-(+)-1, of (±)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide (mosapride) [(±)-1], a new and selective gastroprokinetic agent, were prepared from optically active [4-(4-fluorobenzyl)-2-morpholinyl]methylamines (S)-(-)-4 and (R)-(+)-4, respectively. The requisite (S)-(-)-4 and (R)-(+)-4 were prepared by optical resolution of [4-(4-fluorobenzyl)-2-morpholinyl]methyl p-toluenesulfonate [(±)-5] using (-)- and (+)-N-(p-toluenesulfonyl)glutamic acids, followed by amination of the tosyloxy groups of (R)-(-)-5 and (S)-(+)-5, respectively. The absolute configurations of (R)-(-)-5 and (S)-(+)-5 were determined on the basis of an asymmetric synthesis of (R)-(-)-5 from (S)-(+)-benzyl glycidyl ether [(S)-(+)-11]. Mosapride and its enantiomers, (S)-(-)-1 and (R)-(+)-1, were essentially equipotent in serotonin 5-HT
4 receptor agonistic activity on the electrically evoked contractions in isolated guinea pig ileum.
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Tetsuo NAGANO, Takako TANAKA, Hitomo MIZUKI, Masaaki HIROBE
1994 Volume 42 Issue 4 Pages
883-887
Published: April 15, 1994
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Three water-soluble derivatives of naphthalene endoperoxide were prepared to examine the toxicity of singlet oxygen towards Escherichia coli. On incubation without irradiation, these endoperoxides produce singlet oxygen thermolytically in a dose-dependent manner. The amount of singlet oxygen produced per unit time can be controlled by varying both the incubation temperature and the number of methyl substituents of the naphthalene endoperoxide derivatives. 3-(1, 4-Dihydro-1, 4-epidioxy-4-methyl-1-naphthyl)propionic acid(EP-1), one of the derivatives, inhibited E. coli growth dose- and incubation temperature-dependently and caused E. coli lethality. Furthermore, EP-1 did not induce superoxide dismutase or catalase in E. coli even when the cells were incubated in nutritionally rich medium containing trypticase/soy/yeast extract. Singlet oxygen, one of the reactive oxygen species, did not act as a signal for induction of superoxide dismutase and catalase, in contrast to the actions of superoxide and hydrogen peroxide.
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Akihiro AMBO, Yusuke SASAKI, Kenji SUZUKI
1994 Volume 42 Issue 4 Pages
888-891
Published: April 15, 1994
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Eight dermophin (DM) analogs extended at the C-terminus, based on the sequence of prepro-DM deduced from the cDNA, were synthesized by a simultaneous solid-phase method in which a pair of peptides was synthesized in a single vessel. Six peptides (three pairs) were obtained in satisfactory yields (17-37%). In the opioid receptor-binding assay using a rat brain homogenate, the μ-affinities correlated well to the net positive charges of peptides, and DM-Gly-Glu-Ala-Lys-Lys-Ile-Lys-Arg-NH
2 showed the highest μ-affinity, 115-fold that of DM. But, in the guinea pig ileum assay, extension analogs with net positive charge of 2 to 4 exhibited potencies comparable to or slightly lower than that of DM, even though they possessed 2- to 115-fold higher μ-affinities than DM in the receptor-binding assay.
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Yves L. JANIN, Daniele CARREZ, Jean-Francois RIOU, Emile BISAGNI
1994 Volume 42 Issue 4 Pages
892-895
Published: April 15, 1994
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In order to determine the importance of the pyrrolic nitrogen atom in a series of suitably substituted γ-carbolines derivatives for their cytotoxic and antitumor properties, a series of structurally related benz[h]isoquinolines were synthesized. When compared to the "parent" γ-carbolines, these new compounds showed greatly decreased effects on topoisomerases I and II. Whereas the 8-hydroxylated derivatives retained a significant cytotoxicity, all the new compounds were devoid of antitumor effect in the P388 murine ip-ip system.
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Kiyoshi TANIGUCHI, Kazunori TSUBAKI, Kazuhiko TAKE, Kazuo OKUMURA, Tak ...
1994 Volume 42 Issue 4 Pages
896-902
Published: April 15, 1994
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As part of our search for new agents for the treatment of overactive detrusor, 2, 3- and 3, 4-diphenyl-cyclopentylamines (3), 2, 3-diphenyl-2-cyclopentenylamines (4), and related compounds (5 and 18) were synthesized and evaluated for inhibitory activity (i.v.) against urinary bladder rhythmic contraction in rats. Among them, some compounds involving N-tert-butyl-2, 3-diphenyl-2-cyclopentenylamine (4b) exhibited inhibitory activity against bladder contraction superior to that of terodiline (2). Mydriatic activity (i.v.) of compound 4b in rats, an index of its side effects due to antimuscarinic activity, was found to be relatively weak in comparison with its inhibitory activity against bladder contraction. The pharmacological profile of 4b was examined in comparison with that of terodiline.Most of the objective amines (3, 4, 5) were synthesized by preparation of Schiff bases from the corresponding cyclic ketones (6, 7, 8) and amines in the presence of TiCl
4 in CH
2Cl
2 and subsequent reduction with NaBH
4 in the presence of MeOH in one pot (method A).
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Isamu TERASHIMA, Yuriko YAMAGATA, Naoto YAMAGAMI, Kohfuku KOHDA
1994 Volume 42 Issue 4 Pages
903-906
Published: April 15, 1994
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In order to investigate the chemical characteristics of O
6-methylguanines, the substrate of O
6-methylguanine-DNA methyltransferase, cis-[PtCl(NH
3)
2(O
6, 9-dimethylguanine-7)]NO
3, a 1 : 1 complex of cis-platin with O
6, 9-dimethylguanine, was synthesized and its demethylation rate, pK
a, X-ray structure and cytotoxicity were determined.
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Chisako YAMAGAMI, Miho YOKOTA, Narao TAKAO
1994 Volume 42 Issue 4 Pages
907-912
Published: April 15, 1994
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The capacity factors, k', of 2- and 5-substituted pyrimidines were determined by reversed-phase high performance liquid chromatography (RPLC). The log k' values were correlated with log P by using correction terms for the hydrogen-bond effects of the aza functions of the diazine ring and the substituent. By analogy with the case of the pyrazine series previously studied, a correlation equation with indicator variables categorizing the type and strength of the substituent hydrogen-bonding, and the electronic constant of substituent as additional parameters was obtained to describe the correlation between log k' and log P. Suitable mobile-phase conditions to predict reliable log P values are proposed.
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Yoshiro OHMOMO, Katsuhiko MURAKAMI, Masahiko HIRATA, Yasuhiro MAGATA, ...
1994 Volume 42 Issue 4 Pages
913-916
Published: April 15, 1994
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In developing monoamine oxidase (MAO)-B specific radioligands, N-(2-aminoethyl)-2-chloro-4-[
125I]iodobenzamide ([
125I]FIBA) was conveniently synthesized from its tributylstannyl precursor by an iododestannylation reaction using sodium [
125I]iodide and hydrogen peroxide with high radiochemical yield. The method should be applicable for labeling with
123I, a suitable radioisotope for in vivo imaging with single photon emission computed tomography (SPECT). In vitro binding studies using mouse brain mitochondrial preparations showed that the specific binding of [
125I]FIBA was saturable and of high affinity. Calculated values for K
D and B
max were 201 nM and 9.5 pmol/mg protein, respectively. The [
125I]FIBA binding was effectively prevented by MAO-B specific inhibitors (l-deprenyl, Ro 16-6491, FIBA) or substrate (β-phenethylamine). However, MAO-A specific inhibitor (clorgyline) and substrate (serotonin) had no significant effect. After an intravenous injection into mice, [
125I]FIBA showed high brain uptake (1.64% dose/g at 15-30 min post injection) and long retention (1.11% dose/g at 120 min post injection) in the brain. Good brain-to-blood radioactivity ratios of 2.19 and 2.41 at 60 and 120 min after injection, respectively, were obtained. The in vitro binding data and in vivo characteristics suggested that [
125I]FIBA is potentially useful as a probe for biological studies including specific labeling of MAO-B in vivo as well as in vitro. Moreover, the
123I-labeled counterpart, [
123I]FIBA, might be valuable for non-invasive imaging and mapping of MAO-B in the living brain with SPECT.
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Koichi KAWASAKI, Tomohiko MURAKAMI, Machiko NAMIKAWA, Toyohiko MIZUTA, ...
1994 Volume 42 Issue 4 Pages
917-921
Published: April 15, 1994
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Laminin-related peptides, Try-Ile-Gly-Ser-Arg analogs, were prepared and their inhibitory effects on experimental metastasis were examined. Of the amino acids in the Tyr-Ile-Gly-Ser-Arg sequence, L-Arg was very important and Ile was not essential for the inhibitory effect. To obtain a potent inhibitor of metastasis, hybrids of Tyr-Ile-Gly-Ser-Arg-Gly and 2 types of poly(ethylene glycol) were prepared. The inhibitory effects of the hybrids were more potent than that of Tyr-Ile-Gly-Ser-Arg-Gly.
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Kenji OSAWA, Hideyuki YASUDA, Takashi MARUYAMA, Hiroshi MORITA, Koichi ...
1994 Volume 42 Issue 4 Pages
922-925
Published: April 15, 1994
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The ethanolic extract of Rabdosia trichocarpa leaves showed antibacterial activity against cariogenic mutans streptococci and periodontopathic Porphyromonas gingivalis. Chromatographic separation and purification of the extract afforded ten diterpenes, including one novel ent-kauren type compound named trichoranin. Some of these compounds possess potent antibacterial activity against these oral micro-organisms, indicating that these diterpenes may be useful natural substances for the maintenance of oral health.
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Toshihiro KANMOTO, Yoshihiro MIMAKI, Yutaka SASHIDA, Tamotsu NIKAIDO, ...
1994 Volume 42 Issue 4 Pages
926-931
Published: April 15, 1994
Released on J-STAGE: March 31, 2008
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Phytochemical analysis of the underground parts of Reineckea carnea resulted in the finding of twelve steroidal constituents, five of which appeared to be new compounds and one to be the first isolation from a natural source. The identification and structural determination of the steroidal compounds were established by spectroscopic analysis and hydrolysis. The isolated saponins were evaluated for inhibitory activity on cAMP phosphodiesterase as a primary screening test to find new medicinal materials.
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Tatsuro SHIRAISHI, Shuji KONDO, Hiroshi YUASA, Yoshio KANAYA
1994 Volume 42 Issue 4 Pages
932-936
Published: April 15, 1994
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Several kinds of theophylline granules were prepared by monitoring the power consumption of a high speed mixer while compressing them into tablets. The physical properties of the granules and their tablets were evaluated in order to investigate the optimal physical properties and granulation conditions for tableting. As a result, the granule consisting of a mixture of small agglomerates and bulk powder of similar sizes demonstrated the most favorable physical properties for tableting. Its granulation end point was at the end above first small peak of the power consumption curve.
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Hideki KOHITA, Yasuo MATSUSHITA, Ikuo MORIGUCHI
1994 Volume 42 Issue 4 Pages
937-940
Published: April 15, 1994
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The binding of carprofen (CP) to human serum albumin (HSA) and bovine serum albumin (BSA) was compared using equilibrium dialysis method. The affinity of CP for the primary binding site was BSA>HSA. However, the number of primary binding sites(n
1) was 1.94 on HSA, considerably greater than that on BSA (0.79). The displacement of the binding of CP to HSA and BSA was studied in the presence of phenylbutazone (PB, site I marker), ibuprofen (IB, site II marker) or 2, 3, 5-triiodobenzoic acid (TIB, both site I and II marker). The binding of CP to HSA was altered by PB, IB and TIB, while the binding of CP to BSA was not changed by PB, although it was reduced by IB and TIB. These results suggested that, for the binding of CP, HSA has two major sites (site I and site II), whereas BSA has a single primary site (site II). The binding characteristics of 2-anthracenecarboxylic acid with HSA and BSA were found quite similar to those of CP. Thus, it seemed that long, planar compounds with a carboxyl group at one end can bind to site I and site II on HSA, but only to site II on BSA. The difference between HSA and BSA in the affinity of site I may be due to the difference in the basic and hydrophobic amino acid residues.
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Henry HEYMANN, Yasuhiro TEZUKA, Tohru KIKUCHI, Sutardjo SUPRIYATNA
1994 Volume 42 Issue 4 Pages
941-946
Published: April 15, 1994
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Further investigation of the neutral fraction of the methanolic extract of Sindora sumatrana MIQ. (Leguminosae) has yielded five new sesquiterpenoids : a new trans-isodaucane diol (1), two caryophyllane-type epoxydiols (2, 3), the diacetate of a caryophyllane-type trialcohol (4) and a caryolane-type hydroxy-ketone (5) which possesses an α-C-12 methano bridge. The structure elucidation of the compounds was based mainly on two-dimensional NMR techniques. The biosynthetic significance of the acid-catalyzed rearrangement of 5 to give a clovane-type hydroxyketone (10) is also discussed.
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Ichiro TAKAHASHI, Mikio TSUZUKI, Takashi KEUMI, Hidehiko KITAJIMA, Kim ...
1994 Volume 42 Issue 4 Pages
947-949
Published: April 15, 1994
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1-(1, 2, 3-1H-benzotriazol-1-yl)-2-(4-methylphenyl)-2H-isoindole (1a) is a stable isoindole derivative in the crystalline state. On the basis of the results of X-ray crystallographic analysis, this exceptional stability was explained as follows : the presence of a typical anti-parallel face-to-face stacking between isoindole rings deprives the two reactive centers of an intermolecular approach.
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Yoshinari SATOH, Kazuo OKUMURA, Youichi SHIOKAWA
1994 Volume 42 Issue 4 Pages
950-952
Published: April 15, 1994
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Nilvadipine, I, has already entered clinical use for the treatment of hypertension. In the process of the developing nilvadipine, we prepared the deuteriated analogue of I as an internal standard for the determination of I in human plasma by capillary column gas chromatography-negative-ion chemical-ionization mass spectrometer.Nilvadipine has an asymmetric center at the C-4 position of the dihydropyridine ring, and characterization of the optical isomers with regard to their activity and bioavailability is of interest. Thus, we synthesized both the enantiomers of I by optical resolution via the 5-carboxy derivative (3), which was previously prepared as one of the metabolites of I.
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Satoshi TAKAMATSU, Mun-Chual RHO, Rokuro MASUMA, Masahiko HAYASHI, Kan ...
1994 Volume 42 Issue 4 Pages
953-956
Published: April 15, 1994
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A new testosterone 5α-reductase inhibitor, 8'9'-dehydroascochlorin, was isolated from the cultured mycelium of Verticillium sp. FO-2787. This compound (M.W. : 402, C
23H
27ClO
4) consists of 5-chloroorcylic aldehyde and 2, 3, 4-trimethylcyclohexenone moieties, which are connected via a chain of (2E, 4E)-3-methyl-2, 4-pentadiene. The IC
50 value of the new microbial metabolite for testosterone 5α-reductase activity prepared from rat prostate was 4×10
-4M.
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Kaoru FUJI, Kiyoshi TANAKA, Mija AHN, Maki MIZUCHI
1994 Volume 42 Issue 4 Pages
957-959
Published: April 15, 1994
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The Grignard reactions of mono-benzoylformate ester of 1, 1'-binaphthalene-2, 2'-diol were examined to investigate the complex-induced proximity effect of the phenolic hydroxyl a+ C-2' under different reaction conditions. This hydroxyl group exerted a significant neighboring group participation in the reaction. The nucleophilic addition reaction proceeded with higher diastereoselectivity than that of a series of sterically similarly sized binaphtyl esters recently reported. The halogen ligand in methyl Grignard reagents plays a crucial role in controlling the degree and sense of diastereoselectivity. A plausible mechanism is also proposed.
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Satoru SHIRATORI, Seiji NAGUMO, Takao INOUE, Masahiro NAGAI, Hyung Joo ...
1994 Volume 42 Issue 4 Pages
960-962
Published: April 15, 1994
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Two new diarylheptanoid glycosides, named aceroside XII (7), C
30H
42O
12, [α]
D 70.3°, and aceroside XIII (8), C
25H
34O
8, [α]
D -40.2°, were isolated along with triterpenoids and caffeoyl esters from the branches of Acer triflorum KOM. (Aceraceae). On acid hydrolysis, 7 yielded (-)-centrolobol (9), glucose and apiose. On partial hydrolysis, 7 gave 8 and apiose. Acerosides XII (7) and XIII (8) were determined to be the 4''-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside and the 4''-O-β-D-glucopyranoside of (-)-centrolobol, respectively, on the basis of chemical and spectral evidence.
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Ichiro YAMAWAKI, Masahiro SUZUKI, Kazuo OGAWA
1994 Volume 42 Issue 4 Pages
963-971
Published: April 15, 1994
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Piperazinealkanol ester derivatives of indomethacin were prepared and tested for inhibitory activities against 5-lipoxygenase (5-LO) and cyclooxygenase (CO). They inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) formation by the cytosol of guinea pig polymorphonuclear leukocytes and thromboxane B
2 (TXB
2) formation by washed rabit platelet suspension. Of the test compounds, 2-[4-(2-hydroxyethyl)-1-piperazinyl]-1-phenylethyl 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetate dimaleate (II-8) was found to be the most active dual inhibitor of 5-LO and CO, and its inhibitory potency was higher than that of 2-[4-(3-hydroxypropyl)-1-piperazinyl]-ethyl [1-(4-chlorobenzoyl)-5-methoxy-2-methyl]-3-indolylacetate (CR-1015) (I), the lead compound.
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Daikichi HORIGUCHI, Kazumi SASAMOTO, Hideyuki TERASAWA, Hiroshi MOCHIZ ...
1994 Volume 42 Issue 4 Pages
972-975
Published: April 15, 1994
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A novel macrocyclic ligand for Eu
3+ (24, 30-diphenyl-1, 21 : 4, 6 : 10, 12 : 15, 17-tetraetheno-8, 9, 19, 20-tetrahydro-7H, 18H-dibenzo[b, k]-[1, 4, 7, 10, 13, 16]hexaazacyclooctadecine-8, 19-diacetic acid) was used to label an anti-human chorionic gonadotropin (hCG) monoclonal antibody. The time-resolved fluoroimmunoassay of hCG using this labeled antibody showed a linear response over the range 0.1 to 10 I.U. hCG/ml.
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Ikuo MORIGUCHI, Shuichi HIRONO, Izumi NAKAGOME, Hiroyuki HIRANO
1994 Volume 42 Issue 4 Pages
976-978
Published: April 15, 1994
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The values of log P (partition coefficient in octanol/water) for 22 drugs selected by Rekker et al. [Quant. Struct.-Act. Relat., 12, 152 (1993)] were calculated by the simple method of Moriguchi et al. [Chem. Pharm. Bull., 40, 127 (1992); M] using only 7 parameters, and compared with those obtained from the procedures of Rekker (R), Hansch and Leo (H), and Suzuki and Kudo (S). The descending order of the reliability was M, H, R, and S in the standard error of estimate, R, H, M, and S in the averaged absolute residual-sums, and M, R, H, and S in the regression coefficients between observed and estimated log P values. Serious errors of estimate beyond 2.0 in the absolute residual were seen in R, H, and S, but not in M. These results showed that the method of Moriguchi et al. is not only simple and convenient but also reliable in the application to drugs with complex structures.
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Hisao TOMIDA, Chie NAKAMURA, Setsuo KIRYU
1994 Volume 42 Issue 4 Pages
979-981
Published: April 15, 1994
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A novel method for the preparation of κ-carrageenan/chitosan polyelectrolyte complex (PEC) membrane capsules containing theophylline as a model drug was developed. The theophylline release from the capsules followed zero-order kinetics, and the release rates were independent of pH of the dissolution medium, suggesting that κ-carrageenan/chitosan PEC capsules could be a useful vehicle for controlled-release drug delivery.
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Mugio NISHIZAWA, Shinichi KODAMA, Yoshie YAMANE, Kiyoko KAYANO, Susumi ...
1994 Volume 42 Issue 4 Pages
982-984
Published: April 15, 1994
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Kunio HIROI, Yoshihisa ARINAGA
1994 Volume 42 Issue 4 Pages
985-987
Published: April 15, 1994
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Michael addition of bromomalonate carbanions to chiral α-acylvinylic sulfoxides and the subsequent intramoleculer alkylation yielded optically active acylcyclopropane derivatives with high enantiomeric excess. Stereochemistry of the product was determined by chemical correlation to a compound of known absolute configuration. The mechanism for the asymmetric induction is deduced on the basis of the stereochemical results obtained.
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Tadayuki UNO, Nobuyasu SOWA, Saburo SHIMABAYASHI
1994 Volume 42 Issue 4 Pages
988-990
Published: April 15, 1994
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Hemin was covalently connected to two 9-aminoacridines (9AA) through its two propionates, and the binding properties of this bis-dentate compound (hemin(9AA)
2) to DNA were examined by visible absorption spectroscopy. The binding affinity of the hemin(9AA)
2 was found to be higher than that of the hemin, and this should be attributed to the two linked acridine moieties. The binding constant (K) and the number of binding sites per nucleotide (n) were estimated by Scatchard plot analyses. Though the order of the K value of hemin(9AA)
2 was similar to that of 9AA, the hemin(9AA)
2 was analyzed to have a smaller n value, the order of which was of about 10
-4. The small n value may reflect the sequence specificity of the bis-dentate hemin(9AA)
2 on binding to the DNA.
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Sanan SUBHADHIRASAKUL, Norio AIMI, Hiromitsu TAKAYAMA, Dhavadee PONGLU ...
1994 Volume 42 Issue 4 Pages
991-993
Published: April 15, 1994
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A novel glycosidic alkaloid, hunterioside, together with strictosidinic acid was isolated from Hunteria zeylanica, and the structure was found to be 6'-α-D-glucoside of strictosidinic acid. This isolation is the first finding of a bioside congener of monoterpenoid indole alkaloid glucosides.
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Masayuki YOSHIKAWA, Yoshihiro YOKOKAWA, Yasuhiro OKUNO, Nobutoshi MURA ...
1994 Volume 42 Issue 4 Pages
994-996
Published: April 15, 1994
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Myriocin (thermozymocidin, ISP-I), which was known to exhibit several interesting biological properties such as potent immunosuppressive and antifungal activities, and a new analog Z-myriocin were synthesized from 2-deoxy-D-glucose. This synthetic pathway comprises a stereoselective formation of the chiral α, α-disubstituted amino acid structure in myriocin and Z-myriocin from the isopropylidene six-menbered ketone by using a modified Darzen reaction as its key step.
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Yuko TAKEMURA, Motoharu JU-ICHI, Kenichiro HATANO, Chihiro ITO, Hirosh ...
1994 Volume 42 Issue 4 Pages
997-998
Published: April 15, 1994
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The structure of furobinordentatin, isolated from the root of Citrus yuko (Rutaceae), has been elucidated by spectroscopic studies and a single crystal X-ray analysis as 1. Furobinordentatin is a novel type of bicoumarin composed of two nordentatin (2) units linked with the forming of a dihydrofuran ring.
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Kaoru FUJI, Takeo KAWABATA, Yoshimitsu NANIWA, Toshiumi OHMORI, Manabu ...
1994 Volume 42 Issue 4 Pages
999-1001
Published: April 15, 1994
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Zinc enolates derived from an ester and a lactone, 1 and 4, were found to have enhanced reactivity over the corresponding lithium enolates in asymmetric nitroolefination.
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Tzer Chuan WANG, Hisao KAKEGAWA, Shigeru NAKAISHI, Hitoshi MATSUMOTO, ...
1994 Volume 42 Issue 4 Pages
1002-1004
Published: April 15, 1994
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The inhibitory effects of newely synthesized 4-alkoxy-2, 3, 6-trimethylphenyl D-glycopyranosides on histamine release induced by antigen-antibody reaction were examined. Among the compounds tested, 4-hexoxy-2, 3, 6-trimethylphenyl α-D-mannopyranoside exhibited the strongest inhibitory effect. Furthermore, 4-hexoxy-2, 3, 6-trimethylphenyl α-D-glucopyranoside and α-D-galactopyranoside markedly inhibited antigen-induced histamine release, and their activities were more potent than those of the corresponding β-anomers. These results suggest that these compounds may possess excellent anti-allergic activities.
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