Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Volume 32 , Issue 12
Showing 1-50 articles out of 51 articles from the selected issue
  • TAKUO CHIBA, TETSUZO KATO, ATOMI YOSHIDA, REIMEI MOROI, NAOYUKI SHIMOM ...
    1984 Volume 32 Issue 12 Pages 4707-4720
    Published: December 25, 1984
    Released: March 31, 2008
    JOURNALS FREE ACCESS
    Photoaddition of 2-pyridones and 2-quinolones to diketene or allene gave the head-to-tail adducts, irrespective of the kind of 4-substituent. Therefore, the adducts obtained by the photoaddition of 2-quinolone, 4-methyl-2-quinolone, and their 1-methyl derivatives to diketene (previously assigned as having the head-to-head structure) have now been determined to have the head-to-tail structure. The stereochemistry of the adducts derived from these 2-quinolones and diketene was determined by X-ray crystallographic analysis and nuclear magnetic resonance spectroscopy.
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  • KATSUHIDE MATOBA, FUJIKO KAWAGOSHI, TAKAO YAMAZAKI
    1984 Volume 32 Issue 12 Pages 4721-4725
    Published: December 25, 1984
    Released: March 31, 2008
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    2-Methoxy-4, 4-diphenyl-2, 5-cyclohexadienone (Ib) was synthesized by phenylselenylation of 2-methoxy-4, 4-diphenyl-2-cyclohexenone (Va) followed by oxidative deselenylation of the resultant 6-phenylselenyl derivative (Vc). 4-Dichloromethyl-2-methoxy-4-methyl-2, 5-cyclohexadienone (Ic) was prepared by the Reimer-Tiemann reaction of 2-methoxy-4-methylphenol (IIa).
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  • YASUO ISOMURA, KAZUO KUBO
    1984 Volume 32 Issue 12 Pages 4726-4730
    Published: December 25, 1984
    Released: March 31, 2008
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    Reaction of 6-(3, 5-di-tert-butyl-4-hydroxyphenyl)-2, 3-dihydroimidazo [2, 1-b] thiazole 1-oxide (1) with superoxide anion gave 4-(3, 5-di-tert-butyl-4-hydroxyphenyl)-1-vinylimidazole (2). Compound 2 was also obtained by treatment of 1 with potassium tert-butoxide in dimethyl sulfoxide (DMSO) in the presence of oxygen, while 4-(3, 5-di-tert-butyl-4-hydroxyphenyl)-2-thioxo-1-vinyl-4-imidazoline (3) was obtained together with 2 in the absence of oxygen. When the same reaction was carried out in N, N-dimethyl formamide, 1 gave 2 and 3 in the absence of oxygen, and 4-(3, 5-di-tert-butyl-4-hydroxyphenyl)-1-vinylimidazole-2-sulfonic acid (4) in the presence of oxygen. A possible mechanistic explanation for the formation of these products is presented. Oxygenation of 6-phenyl-2, 3-dihydroimidazo [2, 1-b] thiazole 1-oxide (6) was also examined.
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  • KAZUHISA FUNAKOSHI, HARUAKI INADA, MASATOMO HAMANA
    1984 Volume 32 Issue 12 Pages 4731-4739
    Published: December 25, 1984
    Released: March 31, 2008
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    Isoquinoline 2-oxide (1) reacts with cyanoacetic acid in the presence of Ac2O to afford various types of 1-substituted isoquinolines (2, 4, 6, and 7) and N-ylides (3 and 5a) depending upon the reaction conditions and processing procedures (Table I). The reaction in Ac2O gives initially α-acetoxycarbonyl-1-isoquinolineacetonitrile (2) and 2-isoquinolinio-acetoxycarbonylcyanomethylide (3), and that in Ac2O-dimethylformamide yields only 3. Products 2 and 3 are readily convertible into α-acetyl-1-isoquinolineacetonitrile (4) and 2-isoquinolinio-acetylcyanomethylide (5a), respectively, by processing involving heating. The reaction in ethanol gives ethyl α-cyano-1-isoquinolineacetate (6) and di (1-isoquinolyl) acetonitrile (7). The reaction of 1 with benzoylacetonitrile affords both the corresponding 1-substituted isoquinoline (10) and N-ylide (11). Reactions with ethyl benzoylacetate and, methyl and ethyl acetoacetates produce 1-substituted isoquinolines (12 and 14a, b) and 4-acetoxyisoquinoline (13), no ylide being formed.
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  • MASAICHIRO MASUI, YOSHIYUKI KAMADA, TAEKO IIZUKA, SHIGEKO OZAKI
    1984 Volume 32 Issue 12 Pages 4740-4745
    Published: December 25, 1984
    Released: March 31, 2008
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    Anodic oxidation of α-amino acids with and without a β-hydroxy group was investigated by cyclic voltammetry and controlled potential electrolysis in aqueous carbonate buffer of pH 10. The first wave of the α-amino acids is developed at nearly the same potentials as those observed for the corresponding simple aliphatic amines, showing that a β-hydroxy group does not significantly decrease the first oxidation potential, in contrast to the case of β-alkanolamines. Decarboxylation accompanied by dealkylation is the main reaction process, and a small amount of C-C bond fission also occurs only in the case of the β-hydroxy amino acids.
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  • SHIGEO AMEMIYA, KOICHI KOJIMA, KIYOSHI SAKAI
    1984 Volume 32 Issue 12 Pages 4746-4751
    Published: December 25, 1984
    Released: March 31, 2008
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    A synthesis of 6a-carbaprostaglandin I3 (2) was achieved in which the ω-chain was introduced by Wittig reaction of the optically active aldehyde (3) with the β-oxido ylid (4), followed by removal of the protecting groups to afford a chromatographically separable mixture of the 13 (E)-product (8) and its 13 (Z)-isomer (7). The geometry of the double bond was determined by direct comparison of 8 with a standard sample synthesized by an alternative route (Chart 2). Compound 8 was easily transformed into 2 by a 6-step sequence of reactions (Chart 3). By using a similar technique, (13Z)-6a-carbaprostaglandin I3 (1A) was also synthesized from the 13 (Z)-isomer (6).
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  • YOSHIHISA KURASAWA, KUMI SUZUKI, SHOKO NAKAMURA, KAYANO MORIYAMA, ATSU ...
    1984 Volume 32 Issue 12 Pages 4752-4757
    Published: December 25, 1984
    Released: March 31, 2008
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    Various 3-(1, 2, 4-triazol-5-yl) methylene-2-oxo-1, 2, 3, 4-tetrahydroquinoxalines (4-7, 10, 11) and related compounds (8, 9) were synthesized using 3-hydrazinocarbonylmethylene-2-oxo-1, 2, 3, 4-tetrahydroquinoxaline (2) as a starting material.
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  • TERUSHI HARADAHIRA, MINORU MAEDA, HIROKO OMAE, YUJI YANO, MASAHARU KOJ ...
    1984 Volume 32 Issue 12 Pages 4758-4766
    Published: December 25, 1984
    Released: March 31, 2008
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    Nucleophilic displacement reactions of the 3-O-methyl, and 3-O-benzyl derivatives (5, 11, and 12) of methyl 4, 6-O-benzylidene-2-O-(trifluoromethanesulfonyl)-β-D-glucopyranoside with tetraalkylammonium fluorides in acetonitrile proceeded smoothly to give, with inversion of configuration at C2, the corresponding methyl 2-deoxy-2-fluoro-β-D-mannopyranosides in good yields. Similar treatment of methyl 3-O-benzyl-4, 6-O-benzylidene-2-O-(trifluoromethanesulfonyl)-α-D-glucopyranoside (3) or methyl 3, 4, 6-tri-O-acetyl-2-O-(trifluoromethanesulfonyl)-β-D-glucopyranoside (8) resulted in decreased yield of the fluoro-manno compound. Efficient conversion of these fluorinated intermediates into 2-deoxy-2-fluoro-D-mannose (1) was achieved by heating with acidic reagents. These synthetic sequences could be easily adapted for the preparation of the 18F-labeled analog of 2-deoxy-2-fluoro-D-mannose (1).
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  • EIICHI YOSHII, YOSHIO TAKEUCHI, KEIICHI NOMURA, KEI TAKEDA, SHINJIRO O ...
    1984 Volume 32 Issue 12 Pages 4767-4778
    Published: December 25, 1984
    Released: March 31, 2008
    JOURNALS FREE ACCESS
    A synthetic method for the title compounds has been developed for the syntheses of sarubicin A (1) and granaticin (2). Tetralones (5) and anthracenones (16) were transformed into 1-hydroxy-1-(1-hydroxyethyl) derivatives of tetralins and tetrahydroanthracenes (8, 18) by the route shown in Charts 2 and 4. The diols were dehydrated to allyl alcohols (11, 19) by acid treatment or by reacting their 1'-monoacetates with thionyl chloride followed by alkaline hydrolysis, the choice of procedure being dependent on the structure of the aromatic ring. cis-Dihydroxylation of the olefins by catalytic osmylation using trimethylamine N-oxide as an oxidant afforded the 1R, 2R, 1'R-triols (12, 20) with 98% stereoselectivity, except in the cases of 11a and 19b, where the stereoselectivities were 95 and 90%, respectively. Oxidative ring closure of the triols to the corresponding oxabicycles (13, 21) was achieved by reaction with N-bromosuccinimide under controlled conditions. The intermediate 4-bromo compounds (14, 15) could be isolated in the reactions of 12c, d and underwent smooth cyclization with silver perchlorate in tetrahydrofuran.
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  • EIICHI YOSHII, TADASHI KOMETANI, KEIICHI NOMURA, YOSHIO TAKEUCHI, SHIN ...
    1984 Volume 32 Issue 12 Pages 4779-4785
    Published: December 25, 1984
    Released: March 31, 2008
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    Introduction of a (γ-alkoxycarbonyl) allyl group at the 2 position of 1-naphthol was achieved by a sequence of reactions involving a Claisen rearrangement, as illustrated in Chart 1, in overall yields of 62% (via 2a) and 50% (via 2b). By using the same technique, 5-methoxy- and 4, 5-isopropylidenedioxy-1-naphthols and 4-methoxyphenol were converted to the corresponding 4-aryl-2-butenoates (6a, b and 10), which underwent base-catalyzed cyclization to give dihydrofurans (7a, b and 11). Compounds 7a, b were readily transformed into (±)-nanaomycin A (14). 8, 10-Dimethoxy-1-anthracenone (19) was prepared from 6a in 77% yield by a standard method.
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  • NOBUTAKA FUJII, MOTOYOSHI NOMIZU, KENICHI AKAJI, MASANORI SHIMOKURA, S ...
    1984 Volume 32 Issue 12 Pages 4786-4796
    Published: December 25, 1984
    Released: March 31, 2008
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    Nine peptide fragments were synthesized by known amide-forming reactions as building blocks for the solution synthesis of the hentetracontapeptide amide corresponding to the entire amino acid sequence of human corticotropin releasing factor (hCRF). Amino acid derivatives bearing protecting groups removable by 1M trifluoromethanesulfonic acid-thioanisole in TFA were employed.
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  • NOBUTAKA FUJII, MOTOYOSHI NOMIZU, KENICHI AKAJI, KAZUHIDE WATANABE, MA ...
    1984 Volume 32 Issue 12 Pages 4797-4805
    Published: December 25, 1984
    Released: March 31, 2008
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    The hentetracontapeptide amide corresponding to the entire amino acid sequence of human corticotropin releasing factor (hCRF), deduced from the complementary deoxyribonucleic acid (cDNA) sequence analysis, was synthesized by assembling nine peptide fragments in solution followed by deprotection with 1 M trifluoromethanesulfonic acid-thioanisole (molar ratio 1 : 1) in trifluoroacetic acid. The synthetic peptide significantly elevated the immunoreactive corticotropin level in rat plasma.
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  • YOSHISUKE TSUDA, FUMIYUKI KIUCHI
    1984 Volume 32 Issue 12 Pages 4806-4819
    Published: December 25, 1984
    Released: March 31, 2008
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    The ring A conformations of 4, 4-dimethyl-3-keto steroids can be classified into various geometries on the basis of their torsion angle sign sequence (TASS) of the ring; however, only three were predicted to be possible from theoretical considerations; i.e., C, FB3, and T1 (T2 also occurs in the case of 5-enes) (for details, see the text). They were actually observed by X-ray analyses. The ring A conformation is so flexible that it can readily changes from chair to T1 when a remote structural change such as introduction of an 8β-methyl occurs. Corresponding to this conformational change, the circular dichroism (CD) spectrum of the compound changes its sign from negative to positive. Ring A can also equilibrate in solution with various contributions of chair and T1 conformations depending on their relative energy difference. This equilibrium is greatly affected by remote changes in the structure and also by the solvent, and is sensitively reflected in the CD spectrum which, more or less, shows a double-humped character. The typical double-humped CD spectra of some compounds can thus be well explained. Those compounds should have FC to FB3 conformations at ring A.
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  • YOSHISUKE TSUDA, TAKESHI YAMASHITA, TAKEHIRO SANO
    1984 Volume 32 Issue 12 Pages 4820-4832
    Published: December 25, 1984
    Released: March 31, 2008
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    The circular dichroism (CD) spectra of variously C-8 (and C-14) substituted onocerane-3, 21-diones can be well interpreted by assuming that ring A (and ring D) of the compounds is in equilibrium between chair and twist (T1) forms with variable ratios. This equilibrium was affected by minor structural changes at remote positions and by the polarity of the solvent. Increase of the steric bulkiness of the 8β-substitutent increases the proportion of twist form. The A-ring conformation of compounds which carry an oxygenated function at 8β was greatly affected by changes of the solvent polarity, while that of the compounds without an 8β-oxygenated substituent was almost solvent-independent. These conclusions were supported by measurements of solvent shift in the proton nuclear magnetic resonance (1H-NMR) spectra (TH-effect) of the compounds. The presence of a new kind of steric effect, trivially named the"8α-substituent effect"(for details, see the text), is proposed.
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  • TAKAO KONOSHIMA, TOKUNOSUKE SAWADA, TAKEATSU KIMURA
    1984 Volume 32 Issue 12 Pages 4833-4841
    Published: December 25, 1984
    Released: March 31, 2008
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    Three triterpenoid saponins, gymnocladus saponins A (12), B (18) and C (20), were isolated from the fruits of Gymnocladus chinensis BAILLON (Leguminosae). On the basis of chemical and physicochemical evidence, these saponins were characterized as 2β, 23-dihydroxy-3-O-[α-L-arabinopyranosyl (1→6)-β-D-glucopyranosyl] acacic acid 28, 21-lactone (12), 2β, 23-dihydroxy-3-O-[β-D-glucopyranosyl (1→2)-β-D-glucopyranosyl] acacic acid 28, 21-lactone (18) and 2β, 23-dihydroxy-3-O-[β-D-xylopyranosyl (1→2)-α-L-arabinopyranosyl (1→6)-β-D-glucopyranosyl] acacic acid 28, 21-lactone (20).
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  • TOZO FUJII, TAISUKE ITAYA, TOHRU SAITO, SATOSHI KAWAKATSU
    1984 Volume 32 Issue 12 Pages 4842-4851
    Published: December 25, 1984
    Released: March 31, 2008
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    The rates of the three reactions in the system that produces the rearranged isomers 4a-d and the 5-aminoimidazole derivatives 6a-d from 1-benzyloxy- and 1-(modified benzyloxy)-9-methyladenine perchlorates (2a-d·HClO4) through the isolable ring-opened intermediates 3a-d have been determined at various pH's and ionic strength 1.0 at 40°C. Among four kinds of modified or unmodified benzyloxy groups in these compounds, the 4-nitrobenzyloxy group has been found to cause 2·HClO4 to open its adenine ring most rapidly, whereas it causes 3 to recyclize to 4 most slowly. The reaction of 9-methyladenine 1-oxide (5) with 4-nitrobenzyl bromide in AcNMe2 at room temperature and subsequent treatment of the product with NaClO4 produced 1-(4-nitrobenzyloxy)-9-methyladenine perchlorate (2a·HClO4) in 91% yield. Treatment of 2a·HClO4 with boiling pyridine gave 5 in 84% yield, and reduction of 2a·HClO4 with hydrogen and Pd-C afforded 9-methyladenine (1) in 72% yield, demonstrating the ease with which the 4-nitrobenzyl group can be removed. These results suggest the potential utility of the 4-nitrobenzyloxy group as a control synthon for the preparation of compounds of type 3, which are useful monocyclic intermediates for syntheses of a variety of substituted adenine derivatives.
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  • HIROSHI TAKAHASHI, YUMIKO KUBOTA, HIROKO MIYAZAKI, MASAYUKI ONDA
    1984 Volume 32 Issue 12 Pages 4852-4857
    Published: December 25, 1984
    Released: March 31, 2008
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    Chiral flavanonols and flavan-3, 4-diols have been enantioselectively synthesized from the chiral epoxychalcones (-)-2a and (+)-2b. which are obtained by the asymmetric epoxidation of the chalcone 1 under phase-transfer conditions. The absolute configurations of all the compounds obtained are deduced on the basis of the results obtained by circular dichroic spectroscopy on the dibenzoates (-)-5a, (+)-5b, (+)-8a and (-)-8b.
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  • ISAO KITAGAWA, TOSHIYUKI KAMIGAUCHI, YOSHIHARU IKEDA, MASAYUKI YOSHIKA ...
    1984 Volume 32 Issue 12 Pages 4858-4865
    Published: December 25, 1984
    Released: March 31, 2008
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    By means of a decarboxylative acetoxylation induced by lead tetaacetate and a subsequent nitromethane cyclization reaction, methylated derivatives (1a, 4a, 7a) of three glucuronide-saponins [sakuraso-saponin (1), desacyl-jegosaponin (4), and soyasaponin I (7)] were decomposed selectively at the glucuronide lindage to furnish the methylated genuine aglycones (2, 5, 8) and scyllonitrocyclitol-oligosides (3, 6, 9). The oligosides were further converted to scyllo-aminocyclitololigosides (3a, 6a, 9a), thus accomplishing syntheses of aminocyclitol-oligosides by making use of the oligosaccharide moieties in glucuronide-saponins.
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  • TAKAO SAKAMOTO, HIDEO NAGATA, YOSHINORI KONDO, KAORI SATO, HIROSHI YAM ...
    1984 Volume 32 Issue 12 Pages 4866-4872
    Published: December 25, 1984
    Released: March 31, 2008
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    In order to investigate the structure-activity relationship of betahistine derivatives, a general synthesis of methylated 2-(2-methylaminoethyl) pyridines was developed based on the addition of methylamine hydrochloride to methylated 2-ethynylpyridines under reductive conditions. In addition, the scope and limitations of the reductive addition were briefly examined. For example, the reaction proceeded smoothly with p-nitrophenylacetylene, whereas phenylacetylene itself did not react with methylamine.
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  • OSAMU HOSHINO, MINORU OHTANI, BUNSUKE UMEZAWA, YOICHI IITAKA
    1984 Volume 32 Issue 12 Pages 4873-4882
    Published: December 25, 1984
    Released: March 31, 2008
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    (±)-4-Acetoxy-1-benzyl-6-hydroxy-7-methoxy-2-methyl-1, 2, 3, 4-tetrahydroisoquinolines (3) (R=Me) were proved to be formed by thermal isomerization of o-quinol acetates (2). Reaction of 2 with organic acids gave the (±)-1, 4-trans-and cis-4-acyloxy-1-benzyl derivatives [3 (R=Me, Et, n-C5H11, and tert-Bu)]. With hydrohalic acids, 2 afforded (±)-1-benzyl-5-halogeno-6-hydroxy-7-methoxy-2-methyl-1, 2, 3, 4-tetrahydroisoquinolines [6 (X=Cl, Br)]. Stereochemical aspects of the reactions are discussed.
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  • TADAYUKI KURAISHI, KATSUMI NINOMIYA, TAKAO MURAKAMI, NOBUTOSHI TANAKA, ...
    1984 Volume 32 Issue 12 Pages 4883-4892
    Published: December 25, 1984
    Released: March 31, 2008
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    The fronds of Scypholepia hookeriana J. SM. (Microlepia hookeriana (WALL.) PRESL) afforded four oligoglycosides of a new ent-pimarane-type diterpene, which were named hookerosides A (I), B (II), C (III) and D (IV). The structures were elucidated by means of chemical reactions and spectroscopic methods to be 3α-[O-(3-O-methyl)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinofuranosyloxy]-12α-[(3-O-methyl)-β-D-quinovopyranosyloxy]-(I), 3α-[O-(3-O-methyl)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinofuranosyloxy]-12α-[β-D-fucopyranosyloxy]-(II), 3α-[O-(3-O-methyl)-β-D-glucopyranosyl-(1→2)-α-L-arabinofuranosyloxy]-12α-[β-D-fucopyranosyloxy]-(III) and 3α-[O-β-D-fucopyranosyl-(1→3)-O-β-D-fucopyranosyl (1→2)-α-L-arabinofuranosyloxy]-12α-[β-D-fucopyranosyloxy]-(IV) ent-pimara-8 (14), 15-diene.
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  • KATSUTOSHI SHIMADA, HIDEAKI FUJISAKI, KIYOSHI OKETANI, MANABU MURAKAMI ...
    1984 Volume 32 Issue 12 Pages 4893-4906
    Published: December 25, 1984
    Released: March 31, 2008
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    N-Alkyl-N'-cyano-N"-(substituted phenyl-pyridinylmethyl) guanidine derivatives were synthesized and tested for inhibitory activity against gastric secretion in rats. Several of the compounds synthesized showed an inhibiting activity as potent as that of cimetidine against basal gastric secretion but showed less potent activity than cimetidine against histamine-stimulated gastric secretion. Some structure-activity relationships are discussed.
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  • ISAO HAYAKAWA, TOKIYUKI HIRAMITSU, YOSHIAKI TANAKA
    1984 Volume 32 Issue 12 Pages 4907-4913
    Published: December 25, 1984
    Released: March 31, 2008
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    As part of a search for new synthetic antibacterial agents to combat systemic infection, various analogues of 7-oxo-2, 3-dihydro-7H-pyrido [1, 2, 3-de] [1, 4] benzoxazine-6-carboxylic acids were synthesized. Among the compounds newly synthesized, 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2, 3-dihydro-7H-pyrido [1, 2, 3-de] [1, 4] benzoxazine-6-carboxylic acid (DL-8280) showed potent antibacterial activity against Gram-positive and-negative pathogens, including Psedomonas aeruginosa, and its metabolic disposition was shown in separate experimentals to be favorable.
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  • ISAO HAYAKAWA, NORIO SUZUKI, KAZUNORI SUZUKI, YOSHIAKI TANAKA
    1984 Volume 32 Issue 12 Pages 4914-4922
    Published: December 25, 1984
    Released: March 31, 2008
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    As a part of our search for new antibacterial agents, 5-ethyl-8-oxo-5, 8-dihydrofuro [3, 2-b]-[1, 8] naphthyridine-7-carboxylic acid and its 2, 3-dihydrofuro derivative, the 4-aza analogue of droxacin, were synthesized and their antibacterial activities were tested. Both compounds exhibited high antibacterial activities and a broad antibacterial spectrum. In an attempt to find a suitable method for industrial-scale synthesis of these compounds, several methods for the furan ring cyclization of 6, 7-disubstituted 1, 8-naphthyridine-3-carboxylate derivatives were compared.
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  • YOSHIAKI TANAKA, NORIO SUZUKI, ISAO HAYAKAWA, KAZUNORI SUZUKI
    1984 Volume 32 Issue 12 Pages 4923-4928
    Published: December 25, 1984
    Released: March 31, 2008
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    As part of a series of studies on the synthesis of new antibacterial agents, tetracyclic compounds having a furo [2, 3-g] quinoline moiety as a common structural unit were synthesized, and their antibacterial activities were examined. Among them, 3-methyl-7-oxo-2, 3-dihydro-7H-furo [2, 3-h] pyrido [1, 2, 3-de] [1, 4] benzoxazine-6-carboxylic acid (4c) exhibited the most potent antibacterial activity against Gram-positive and-negative organisms, including Pseudomonas aeruginosa, and it showed low acute toxicity to mice.
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  • TAMOTSU NIKAIDO, TAICHI OHMOTO, TARO NOMURA, TOSHIO FUKAI, USHIO SANKA ...
    1984 Volume 32 Issue 12 Pages 4929-4934
    Published: December 25, 1984
    Released: March 31, 2008
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    Adenosine 3', 5'-cyclic monophosphate (cyclic AMP) phosphodiesterase inhibition by phenolic constituents of mulberry tree was studied. The structure-inhibitory activity relationships were studied in 56 derivatives of prenylflavonoids, prenylchalcones and Diels-Alder type adducts. Diels-Alder type adducts of chalcones and dehydroprenylflavonoids or dehydroprenyl-2-arylbenzofurans differed from prenylflavonoids and prenylchalcones in the inhibitory activity and inhibitory type (determined by means of Dixon plots).
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  • MUNEKAZU IINUMA, KIYOSHI IWASHIMA, SHIN MATSUURA
    1984 Volume 32 Issue 12 Pages 4935-4941
    Published: December 25, 1984
    Released: March 31, 2008
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    Seven naturally occurring flavones oxygenated at C-2', C-4' and C-5' in ring B were synthesized, together with their isomers, to confirm the proposed structures. The synthesized flavones 1, 2, 3a, 5, 7 and 8 were identical with the corresponding natural flavones, but 4a was not. The spectral properties of these flavones are discussed.
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  • HISAYUKI KANAMORI, IKUNORI SAKAMOTO, MARI MIZUTA, OSAMU TANAKA
    1984 Volume 32 Issue 12 Pages 4942-4945
    Published: December 25, 1984
    Released: March 31, 2008
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    Good separation of seven mutagenic xanthones present in Swertiae Herba was accomplished by thin-layer chromatography (TLC) on silica gel plates. The conditions for quantitative analysis of these xanthones by TLC-densitometry were investigated, and this TLC-densitometry was applied to the analysis of the constituents of the commercial Swertiae Herba and to the determination of the time courses of their extraction with hot water. The relationship between xanthone content and mutagenicity is discussed.
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  • YASUKO ISHII, HISAYUKI TANIZAWA, YOSHIO TAKINO
    1984 Volume 32 Issue 12 Pages 4946-4950
    Published: December 25, 1984
    Released: March 31, 2008
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    We have developed a new method for the determination of barbaloin, the main laxative component in Aloe. Our method utilizes fluorophotometry based on Schoutelen's reaction which takes place between barbaloin and borax. Barbaloin was heated in 0.2 M borax solution at 60°C for 5 min, then the reaction mixture was immediately diluted with an equal volume of water and the mixture was cooled. The yellow-green fluorescence intensity of the solution was measured at excitation and emission wavelengths of 383 and 510 nm. Barbaloin contents in Aloe pulv. and pulv. of aloe leaf were determined by using this method. The data were compared with those obtained by the methods of the European pharmacopeia (EP) and the German pharmacopeia (DAB 7). It was concluded that our method is superior to the EP and DAB 7 methods in sensitivity, accuracy and simplicity.
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  • TAKASHI NISHIKAWA, MASAYUKI SAITO, HIROAKI KUBO
    1984 Volume 32 Issue 12 Pages 4951-4957
    Published: December 25, 1984
    Released: March 31, 2008
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    A competitive nephelometric immunoassay that is based on the inhibition of immunoprecipitation by a hapten was improved in specificity and in sensitivity for theophylline by the use of a heterologous combination of the assay reagents. Each of two theophylline derivatives, theophylline-7-propionic acid and theophylline-8-butyric acid, was conjugated to bovine serum albumin. These conjugates were injected into rabbits to raise anti-theophylline antiserum. Each derivative was also conjugated to human serum albumin. The competitive nephelometric immunoassay was performed by combined use of this human serum albumin conjugate with the antiserum. This immunoassay system allowed two homologous combinations and two heterologous combinations. Of these four combinations, the heterologous combination of the conjugate of (theophylline-7-propionyl)-(human serum albumin) with the antiserum against (theophylline-8-butyryl)-(bovine serum albumin) gave the most sensitive immunoassay for theophylline with the lowest interference by caffeine.
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  • TAKASHI NISHIKAWA, MASAYUKI SAITO, HIROAKI KUBO
    1984 Volume 32 Issue 12 Pages 4958-4962
    Published: December 25, 1984
    Released: March 31, 2008
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    We developed a competitive nephelometric immunoassay for the determination of ethosuximide. The method was based on the inhibition of immunoprecipitation by a hapten. Each of two ethosuximide derivatives, ethosuximide acetic acid and ethosuximide butyric acid, was conjugated to bovine serum albumin. These conjugates were injected into rabbits to raise anti-ethosuximide antisera. Each derivative was also conjugated to human serum albumin. These two conjugates were allowed to react with the two antisera in combination to form precipitates. Ethosuximide and its derivatives quantitatively inhibited these four precipitation reactions. The results indicated that the anti-(ethosuximide butyrate) antiserum recognized the bridge moiety better than the anti-(ethosuximide acetate) antiserum. Of the four combinations, the heterologous combination of the anti-(ethosuximide butyrate) antiserum with the (ethosuximide acetyl)-human serum albumin conjugate gave the most sensitive immunoassay for ethosuximide.
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  • YOSHITERU TAKAHASHI, KAZUKO NAKASHIMA, HIROSHI NAKAGAWA, ISAO SUGIMOTO
    1984 Volume 32 Issue 12 Pages 4963-4970
    Published: December 25, 1984
    Released: March 31, 2008
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    The effects of grinding and drying (removal of water of crystallization) processes on the solidstate stability of ampicillin trihydrate were studied. The ground samples became more unstable as the grinding time increased. This phenomenon is considered to be due to a greater freedom of movement of water molecules, which are sufficiently free to participate in a solid-state hydrolytic reaction in the impaired lattice induced by grinding. A stabilization effect was observed when the ground sample was stored at high humidity, although ampicillin was susceptible to hydrolysis. This effect was interpreted in terms of a decrease of the ability of water molecules to move within the crystal. The dehydration of ampicillin trihydrate resulted in a higher disorder of the crystal structure. Partially dehydrated samples were unstable. However, and almost completely dehydrated sample was relatively stable because of the virtual absence of water able to participate in the hydrolytic reaction
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  • YOSHIYUKI KOIDA, MASAO KOBAYASHI, GOICHI HIRATA, MASAYOSHI SAMEJIMA
    1984 Volume 32 Issue 12 Pages 4971-4978
    Published: December 25, 1984
    Released: March 31, 2008
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    The effect of molecular weight (M^-) of polyisolbutylene (PIB), used as a coacervation-inducing agent in the preparation of ethylcellulose (EC) microcapsules (MC) in cyclohexane, was studied with ascorbic acid as the core material. PIBs of various M^- were obtained by the fractionation of commercially available PIB and microencapsulation was performed. It was found that aggregation of MC decreased with increasing M^- and was almost wholly prevented at M^- of above 6×105 and that the release rate of ascorbic acid became minimum at M^- of around 2×105. The effect of mixing of commercially available high M^-PIB (9.5×105) and low M^-PIB (3×104) on microencapsulation was also investigated. In this case the release rate became minimum at a mixing ratio of around 1 : 4 (high M^- : low M^-). With increase of low M^-PIB, average wall thickness and compactness increased and the wall became less uniform. Thus, it was presumed that the most prolonged MC was produced when the compactness, thickness and uniformity of the wall were well balanced. The influence of M^- of PIB on the coacervation process was also investigated by measuring the volume fraction, EC contents and viscosity of the coacervate phase. From these data, it was presumed that M^- of PIB affects the properties of the coacervation droplet, and consequently influences the properties of the wall formed from the droplet.
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  • KAZUYUKI HIRANO, YOSHIHITO WATANABE, TETSUO ADACHI, YOSHIMASA ITO, MAM ...
    1984 Volume 32 Issue 12 Pages 4979-4985
    Published: December 25, 1984
    Released: March 31, 2008
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    The crossreactivity between human α-fetoprotein and serum albumin in their unfolded forms was investigated by immunological methods. On enzyme immunoassay and immunostaining, reduced and carboxyamidomethylated human α-fetoprotein and serum albumin crossreacted with antibodies to their unfolded forms and weakly reacted with those to their native forms. Peptide fragments of human α-fetoprotein and serum albumin cleaved only by cyanogen bromide were nonreactive with antibodies to their native forms and with those to their unfolded forms. However, after reduction and carboxyamidomethylation, the peptide fragments prepared were mostly crossreactive with antibodies of their unfolded forms, but not with those of their native forms. While the native forms of human α-fetoprotein and serum albumin and their peptide fragments obtained by cyanogen bromide cleavage retained binding abilities with bilirubin and anilinonaphthalene sulfonate, the unfolded forms had no binding abilities. These findings suggest that the binding abilities, proposed to be related to the biological functions of human α-fetoprotein and serum albumin, are mainly attributable to their conformational character rather than to their primary sequences.
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  • NOBUYOSHI KANENIWA, KANJI IMAGAWA, MAKOTO OTSUKA
    1984 Volume 32 Issue 12 Pages 4986-4993
    Published: December 25, 1984
    Released: March 31, 2008
    JOURNALS FREE ACCESS
    The compression process of cephalexin (CEX) powder was studied by using a tabletting machine with punches of 0.7, 1.0 and 2.0 cm diameter, and the maximum compression stress (MP), the compression loss energy (LE), the elastic energy (EE), the compression energy (CE), the hardness of the tablet (H) and the elastic recovery (R) were measured. The compression process followed Bal'shin's equation, and was independent of sample weight in the range of 110 to 300 mg. In the compression process with the 0.7 cm punch the plot of the compression stress versus the thickness of the powder bed was shifted to the slightly higher pressure side as compared with the plots for the 1.0 and 2.0 cm punches, presumably because the die wall friction of the 0.7 cm punch was larger than that of the 1.0 and 2.0 cm punches. Elastic behavior appeared on high-pressure compression of CEX powder. The Young's modulus obtained from the relation between MP and R was calculated to be 4.75×109 dyn/cm2. The tensile strength (TS) and R value increased with increasing value of MP.
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  • CHISAKO YAMAGAMI, HIDEKO TAKAMI, KAZUKO YAMAMOTO, KYOKO MIYOSHI, NARAO ...
    1984 Volume 32 Issue 12 Pages 4994-5002
    Published: December 25, 1984
    Released: March 31, 2008
    JOURNALS FREE ACCESS
    Partition coefficients (octanol-water), P. for a series of phenylacetanilides, PhCH2CONHC6H4-Xm, p (I), were determined by the shaking-flask method. The observed π values (π=log P(I)-log ρphCH2CONHPh) were analyzed in terms of substituent effects to give the relationship π=0.833πx+0.788σx+0.040, where πx=logphx-logphH. We also determined and analyzed the capacity factors for these compounds, K', which are regarded as an alternative hydrophobic parameter, by using reversed-phase high-performance liquid chromatography (RP-HPLC) in different H2O-organic solvent mixtures. It was observed that the substituent effects on the log κ' value are influenced by the organic modifier in the mobile phase. Linear relationships between log P and log κ' were generally observed but there were some outliers such as OH, CN and NO2 derivatives. The deviation of phenolic compounds from the log ρ-log κ' linearity can be explained in terms of the difference in partitioning behavior between the octanol-water system and the lipophilic stationary phase-mobile phase system.
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  • CHISAKO YAMAGAMI, NARAO TAKAO, MITSUYO TANAKA, KAZUYOSHI HORISAKA, SYO ...
    1984 Volume 32 Issue 12 Pages 5003-5009
    Published: December 25, 1984
    Released: March 31, 2008
    JOURNALS FREE ACCESS
    A series of o-, m-, and p-substituted anilides of phenylacetic acid were tested for anticonvulsant activity in mice by means of the maximal electroshock seizure test and structure-activity relationships were quantitatively studied by Hansch analysis. The potencies (-log ED50) for meta derivatives were shown to depend parabolically on log P (P is the 1-octanol-H2O partition coefficient) and linearly on the Hammett σ values. The derived correlation predicted that the maximum activity would be obtained when log P is about 2. 3 and an electron-donating substituent is introduced. This conclusion is consistent with the structural requirements recently reported for m-and p-substituted benzyl N, N-dimethylcarbamates. Most of the o-and p-substituted compounds exhibited lower activities than m-derivatives. The effects of ortho and para substitutions are discussed.
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  • MASAO HATTORI, TATSUYA SAKAMOTO, YOSHIYUKI ENDO, NOBUKO KAKIUCHI, KYOI ...
    1984 Volume 32 Issue 12 Pages 5010-5017
    Published: December 25, 1984
    Released: March 31, 2008
    JOURNALS FREE ACCESS
    As a part of our studies on the metabolism of active components from traditional Chinese medicines, magnolol was orally administered to rats. The urinary and fecal metabolites were analyzed by high-performance liquid chromatography and liquid chromatography-mass spectrometry, and their structures were determined to be tetrahydromagnolol (M1), 5-(1-propen-1 (E)-yl)-5'-propyl-2, 2'-dihydroxybiphenyl (M2), 5-allyl-5'-propyl-2, 2'-dihydroxybiphenyl (M3), isomagnolol (5, 5'-di (1-propen-1 (E)-yl)-2, 2'-dihydroxybiphenyl) (M4), 5-allyl-5'-(1-propen-1 (E)-yl)-2, 2'-dihydroxybiphenyl (M5). On the other hand, magnolol was transformed to M4 and M5 together with small amounts of M2 and M3 by anaerobic incubation with rat feces. This suggests that the isomerization of magnolol in the rat could be carried out by the action of intestinal bacteria.
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  • SHUNSUKE KAZAMA, MAMORU KAMIYA, YUKIO AKAHORI
    1984 Volume 32 Issue 12 Pages 5018-5022
    Published: December 25, 1984
    Released: March 31, 2008
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    Conformational peculiarity of 10-(9H-xanthenylidene)-9 (10H)-anthracenone was studied in relation to the temperature effect in the photochemical cyclization and reduction reactions. On the basis of the experimental result that the temperature effect is negative for the former reaction but positive for the latter reaction, it was concluded that the population of the planar structure of the above molecule in solution decreases gradually at higher temperatures in favor of a twisted structure which contributes to the radical formation. This conclusion is consistent with the results of our previous polarographic and electron spin resonance studies of some thermochromic ethylenes. On the other hand, the planar structure of the molecule appears to be predominant over a wide range of temperature in the crystal state.
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  • EMIKO SHIMIZU, TOSHIAKI TOMIMATSU, TOSHIHIRO NOHARA
    1984 Volume 32 Issue 12 Pages 5023-5026
    Published: December 25, 1984
    Released: March 31, 2008
    JOURNALS FREE ACCESS
    Three flavone derivatives, TT-a (1), TT-b (2) and TT-c (3), were isolated from Thalictrum thunbergii DC. Compound 1 was characterized as apigenin 7, 4'-bis-O-β-D-allopyranoside, and 2 and 3 were found to be acetyl derivatives of TT-a (1).
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  • MASAHITO OCHIAI, EIICHI FUJITA, MASAO ARIMOTO, HIDEO YAMAGUCHI
    1984 Volume 32 Issue 12 Pages 5027-5030
    Published: December 25, 1984
    Released: March 31, 2008
    JOURNALS FREE ACCESS
    A new general method for the synthesis of allyl ethers and allyl acetates is described. Allylmetal (group IVb) compounds, on treatment with thallium (III) salts in alcohols or acetic acid, gave the corresponding allyl ethers or allyl acetates in good yields. The reaction was successfully applied to the synthesis of the 6-membered cyclic ether 20 via the intramolecular, thallium (III)-mediated allylation reaction of the allylsilane 18.
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  • YOSHIRO KOBAYASHI, TAKABUMI NAGAI, ITSUMARO KUMADAKI
    1984 Volume 32 Issue 12 Pages 5031-5035
    Published: December 25, 1984
    Released: March 31, 2008
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    The reaction of hexafluoroacetone with phenyl-substituted allyl compounds was found to give the ene products. Thus, allylbenzene gave 1, 1, 1-trifluoro-5-phenyl-2-(trifluoromethyl) pent-4-en-2-ol. Allyl phenyl ether and thioether gave the corresponding ene products. The product from the latter cyclized to 5-phenylthio-2, 2-bis (trifluoromethyl) tetrahydrofuran. N-Allyl-N-methylaniline reacted with the ketone to give the 4-(1, 1, 1, 3, 3, 3-hexafluoro-2-hydroxy-2-propyl) derivative via the Friedel-Crafts reaction, and this compound further reacted in the ene reaction to give unusual products.
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  • NOBUTAKA FUJII, YOSHIO HAYASHI, SHIROH FUTAKI, KENICHI AKAJI, HARUAKI ...
    1984 Volume 32 Issue 12 Pages 5036-5039
    Published: December 25, 1984
    Released: March 31, 2008
    JOURNALS FREE ACCESS
    N-Succinimidyl-p-and m-(2-nitrovinyl)-benzoates (SNVB) were introduced as heterobifunctional conjugating reagents for immunoassay. These reagents smoothly react with SH-compounds, such as cysteine or mercaptopropionic acid, in acidic media, then with alanine under slightly basic conditions to yield the corresponding benzoylalanine derivatives. On the basis of these model experiments, the feasibility of practical use of these reagents is discussed.
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  • TADASHI SASAKI, MASATOMI OHNO, EIKOH ITO
    1984 Volume 32 Issue 12 Pages 5040-5043
    Published: December 25, 1984
    Released: March 31, 2008
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    2-Methanesulfonyl-5-phenyl-1, 3, 4-oxadiazole (4) reacted with 3-aminopropanol and 2-aminoethanethiol in the presence of triethylamine to give displaced and rearranged products 2-(5, 6-dihydro-4H-1, 3-oxazin-2-yl)-(6b) and 2-(2-thiazolin-2-yl) benzhydrazide (9), which were further cyclodehydrated by heating to give the corresponding fused s-triazoles (7) and (10), respectively. In the case of the reaction with a diaminoalkane only the 1 : 2 adduct (8) was obtained.
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  • TETSUHIDE KAMIJO, HIROMU HARADA, KINJI IIZUKA
    1984 Volume 32 Issue 12 Pages 5044-5047
    Published: December 25, 1984
    Released: March 31, 2008
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    The esterification of carboxylic acids proceeded easily in a one-pot reaction with 1, 1'-carbonyldiimidazole in the presence of a reactive halide under neutral reaction conditions in high yields.
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  • MASAMI INOUE, SHIGEKAZU OHNISHI, RYOICHI TANAKA, SABURO ENOMOTO
    1984 Volume 32 Issue 12 Pages 5048-5050
    Published: December 25, 1984
    Released: March 31, 2008
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    The polymerization of glycine was carried out in the presence of anilinium tripolyphosphate at 150°C under nitrogen. The conversion reached 81% after 15 h. The polyglycine obtained was slightly soluble in water and the mean molecular weight of the polymer was 800. Several neutral amino acids also gave conversions of 33 to 71%.
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  • MICHINORI KUBO, HIDEAKI MATSUDA, YOSHIYUKI KIMURA, HIROMICHI OKUDA, SH ...
    1984 Volume 32 Issue 12 Pages 5051-5054
    Published: December 25, 1984
    Released: March 31, 2008
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    The effects of various flavonoids isolated from the roots of Scutellaria baicalensis on the histamine release from mast cells were investigated. Many of the flavonoids (wogonin, wogonin-7-O-D-glucuronide, baicalein, skullcapflavone II, (2S)-2', 5, 6', 7-tetrahydroxyflavanone, (2R, 3R)-2', 3, 5, 6', 7-pentahydroxyflavanone and 2', 5, 5', 7-tetrahydroxy-6', 8-dimethoxyflavone) inhibited the histamine release from rat mast cells induced by compound 48/80.
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  • MUTSUO KOZUKA, AKIRA INADA, TAKAO KONOSHIMA, TOKUNOSUKE SAWADA
    1984 Volume 32 Issue 12 Pages 5055-5058
    Published: December 25, 1984
    Released: March 31, 2008
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    A new aporphine alkaloid, praecoxine (1), was isolated from the root of Parabenzoin praecox (SIEB. et ZUCC.) NAKAI. The alkaloid was shown to be identical with N-methylhernagine, (S)-(+)-1, 2, 11-trimethoxy-10-hydroxyaporphine (1), on the basis of chemical transformations and spectral evidence. The occurrence of nandigerine (10) in the root and the stem wood was also proved.
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  • TSUTOMU OIKAWA, TAKAO IWAGUCHI
    1984 Volume 32 Issue 12 Pages 5059-5063
    Published: December 25, 1984
    Released: March 31, 2008
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    Aspartic proteinase was purified from guinea pig peritoneal macrophages (Mφs) by pepstatin-Sepharose, Sephadex G-150 and diethylaminoethyl-cellulose column chromatographies. The purified enzyme was homogeneous on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. In isoelectric focusing, the enzyme was resolved into four peaks which had pIs of 6.04, 6.53, 7.11 and 7.75. The molecular weight of the enzyme was estimated to be 43000 by gel filtration and 45000 by SDS-polyacrylamide gel electrophoresis. The enzyme was adsorbed on a column of concanavalin A-Sepharose and was eluted with α-methyl mannoside, indicating that it is a glycoprotein. The pH optimum of the enzyme for hydrolysis of acid-denatured hemoglobin was around 3.2. The enzyme was completely inhibited by pepstatin, but not by other chemicals tested, including antipain and leupeptin. Since the properties of the enzyme from Mφs resemble those of cathepsins D isolated from the lysosome of other tissues, it can be concluded that this enzyme is cathepsin D (EC 3.4.23.5).
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  • Masanori Somei, Fumio Yamada
    1984 Volume 32 Issue 12 Pages 5064-5065
    Published: December 25, 1984
    Released: March 31, 2008
    JOURNALS FREE ACCESS
    A convenient, short synthesis of (±)-6, 7-secoagroclavine is developed having a 36% overall yield, high regio-and stereo-selectivity, and using no protecting groups.
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