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Volume 37, Issue 4
Displaying 1-50 of 69 articles from this issue
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Application of Dibutyltin Oxide Method to Regioselective Acylation and Alkylation of Tylosin at C-4"Kohki KIYOSHIMA, Michiko SAKAMOTO, Tomoyuki ISHIKURA, Yasuo FUKAGAWA, ...1989 Volume 37 Issue 4 Pages 861-865
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS4"-O-Acyl-, 4"-O-alkyl- and 4"-deoxy-tylosin derivatives were synthesized using 2'-O-acetyl-3", 4"-O-(dibutyl-stannio)tylosin as a synthetic intermediate. The in vitro biological evaluation showed that the new derivatives were active against macrolide-resistant clinical isolates of bacteria and mycoplasmas, and that they were resistant to hepatic esterase.View full abstractDownload PDF (803K) -
Chuzo IWATA, Yoshiji TAKEMOTO, Hitoshi KUBOTA, Minoru YAMADA, Shuji UC ...1989 Volume 37 Issue 4 Pages 866-869
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA total synthesis of (±)-lubiminol (2) from the allylic alcohol (3) was achieved through the introduction of a bis(ethoxycarbonyl)methyl group with inversion at C2 followed by hydrogenation of the C6-C7 double bond and transformation of the bis(ethoxycarbonyl)methyl group into isopropenyl. On the other hand, the alcohol (1) was an inefficient starting material for the synthesis.View full abstractDownload PDF (662K) -
Masaru KIHARA, Kuniyoshi OHNISHI, Suwanna VANGVERAVONG, Shigeru KOBAYA ...1989 Volume 37 Issue 4 Pages 870-876
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS8-Hydroxy-5, 6, 7, 8-tetrahydrodibenz[c, e]azocines 4b, c and their methoxy and methylenedioxy derivatives 7a-c and 8a-c were prepared by cyclization of O-protected 1-phenyl-2-aminoethanols 6b, c, 9a-c and 10a-c with zerovalent nickel, followed by hydrolysis of the resulting O-protected azocines 4d, e, 7d-f and 8d-f, respectively. The half-tub conformation of the tetrahydroazocine ring of these 8-hydroxydibenz[c, e]azocines and the quasi-equatorial configuration of the 8-hydroxy group were supported by the proton nuclear magnetic resonance spectra.View full abstractDownload PDF (949K) -
Takuo CHIBA, Jun-ichi SAKAKI, Satoshi KOBAYASHI, Toshio FURUYA, Noriyo ...1989 Volume 37 Issue 4 Pages 877-882
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSMethyl penam-(3S)-carboxylate (methyl 7-oxo-1-thia-4-azabicyclo[3.2.0]heptane-(3S)-carboxylate), the basic skeleton of penicillin-type β-lactams, has been synthesized from D-cysteine methyl ester and tert-butyl formylacetate in three steps through the formation of the thiazolidinylacetic acid followed by cyclization by Mukaiyama-Ohno's procedure. Use of D-penicillamine methyl ester as well as the dimethyl derivative of tert-butyl formylacetate in the above method provides a general synthetic route to a variety of methyl penam-(3S)-carboxylates having methyl groups at the 2 and/or 6-positions.The yields as well as stereoselectivity at C-5 in the cyclization step are shown to be strongly dependent upon the patterns of substituents on the thiazolidinylacetic acid skeleton, and the reason for this is discussed from the mechanistic viewpoint.View full abstractDownload PDF (1044K) -
Ryuzo YOSHIOKA, Osamu OHTSUKI, Masaru SENUMA, Tetsuya TOSA1989 Volume 37 Issue 4 Pages 883-886
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA practical preparation of D-aspartic acid β-methyl ester [D-Asp(OMe)], a raw material for the antibiotic aspoxicillin, has been developed by the use of a second-order asymmetric transformation. The diastereomeric resolution of DL-Asp(OMe) with (-)-1-phenylethanesulfonic acid (PES) resulted in salt formation of less soluble D-·(-) and more soluble L-·(-) in acetonitrile. The soluble L-·(-) was easily epimerized into DL-·(-) by heating it in acetonitrile in the presence of catalysts. Attempted fractional crystallization of DL-·(-) or L-·(-) under such epimerizing conditions led to the desired D-·(-) in 90% yield via equilibrium asymmetric transformation in a solid-liquid heterogeneous system. Details of optimum techniques for the asymmetric transformation are presented.From these results, unique preparation processes of both D-Asp(OMe) and D-p-hydroxyphenylglycine, important intermediate materials for aspoxicillin, have been achieved by asymmetric transformation using chiral PES as the resolving agent.View full abstractDownload PDF (717K) -
Fumiko ABE, Rong-Fu CHEN, Tatsuo YAMAUCHI, Nobuhiro MARUBAYASHI, Ikuhi ...1989 Volume 37 Issue 4 Pages 887-890
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA new indole alkaloid, named alschomine, was obtained from the leaves of Alstonia scholaris planted in Taipei, along with its C-5 isomer, isoalschomine, and the known alkaloids of this plant, picriinine, picralinal and nareline. The structure of alschomine was determined by X-ray analysis, supported by spectral considerations.View full abstractDownload PDF (570K) -
Yasuyuki KITA, Takayuki YAKURA, Hiroaki TERASHI, Jun-ichi HARUTA, Yasu ...1989 Volume 37 Issue 4 Pages 891-894
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSOxidation of ethynylcarbinols (4a-g), prepared easily from ketones, with a hypervalent iodine reagent, phenyliodosyl bis(trifluoroacetate) (PIFA), in chloroform-acetonitrile-water gave the dihydroxyacetonyl compounds (6a-g) in high yields.View full abstractDownload PDF (639K) -
Hikaru OKABE, Tsuneatsu NAGAO, Shizuko HACHIYAMA, Tatsuo YAMAUCHI1989 Volume 37 Issue 4 Pages 895-900
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSFour oleanane-type triterpene saponins named luperosides I, J, K and L were isolated as their methyl esters from the MeOH extract of the herb of Luffa operculata COGN., and their structures were elucidated on the basis of chemical and spectral evidence. Luperosides I and J are 3-O-[β-D-galactopyranosyl-(1→2)-[α-L-arabinopyranosyl-(1→3)]-β-D-glucopyranosyluronic acid]-28-O-[β-D-xylopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-β-D-quinovopyranosyl] gypsogenin (I) and 3-O-[β-D-galactopyranosyl-(1→2)-[α-L-arabinopyranosyl-(1→3)]-β-D-glucopyranosyluronic acid]-28-O-[β-D-xylopyranosyl-(1→3)-β-D-xylopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-β-D-quinovopyranosyl] gypsogenin (J), respectively. Luperosides K and L are quillaic acid glycosides corresponding to luperosides I and J, respectively.View full abstractDownload PDF (983K) -
Takeaki NAITO, Yumiko HIRATA, Okiko MIYATA, Ichiya NINOMIYA, Masatoshi ...1989 Volume 37 Issue 4 Pages 901-906
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA formal total synthesis of (±)-deserpidine (1) was accomplished by preparing the known synthetic precursors, two hydroxyesters 19 and 20, via a route involving regioselective formation of the 18-methoxyenone 10a followed by regioselective C-acylation of the enone 10a.View full abstractDownload PDF (949K) -
Takuzo HISANO, Kazunobu HARANO, Toshikazu MATSUOKA, Sigeru WATANABE, T ...1989 Volume 37 Issue 4 Pages 907-911
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSIn connection with the stereoselective exo cycloaddition in the 1, 3-dipolar reaction of 3, 5-lutidine N-oxide and N-arylmaleimides, the cycloaddition behavior of some nitrones toward N-phenylmaleimide was investigated. In the reaction of cyclic nitrones with N-phenylmaleimide, pairs of isomers were isolated in a crystalline state. The low-temperature nuclear magnetic resonance measurements of the adducts suggested that the compounds are conformational isomers with regard to the ring inversion brought about by the mobility of the lone pair on nitrogen. The observed reactivity and regiochemistry are discussed in terms of frontier molecular orbital considerations.View full abstractDownload PDF (814K) -
Shigeki SASAKI, Kenji KOGA1989 Volume 37 Issue 4 Pages 912-919
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA novel approach to the mimicking of enzyme-catalyzed bond-forming reactions has been examined using multi-functionalized chiral crown ethers. In addition to the 18-crown-6 moiety as a binding site, the hosts have one thiol and one thio ester with an N-protected α-amino acid or a peptide, and have successfully achieved peptide synthesis in an enzyme-mimetic reaction mode. This new method involves the following three key reactions. (1) Intra-complex thiolysis : the host carries out the rapid intra-complex thiolysis of α-amino acid ester salts to form the dithioester, corresponding to the assembly of two guests by the host. (2) Amide formation : intramolecular aminolysis occurs between the bound guests to form the amide bond. (3) Peptide chain elongation : as the thiol reactive group is regenerated, the above two reactions are repeated to elongate the peptide chain. Formal turnover of the enzyme model has been demonstrated by the synthesis of a tetrapeptide derivative by the repetition of the above processes.View full abstractDownload PDF (1205K) -
Takashi YOSHIDA, Katsumi TANAKA, Xin-Min CHEN, Takuo OKUDA1989 Volume 37 Issue 4 Pages 920-924
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSFour new hydrolyzable tannins, laevigatins A-D, were isolated from Rosa laevigata, a Chinese medicinal plant.Among them, laevigatin B, laevigatin C and laevigatin D, were dimeric ellagitannins closely related to agrimoniin, which has a dehydrodigalloyl group in the molecule. Nine known tannins, including agrimoniin and agrimonic acids A and B, were also isolated. Structures of new tannins were assigned on the basis of proton and carbon-13 nuclear magnetic resonance spectral data, and chemical conversion of agrimonic acid A to laevigatin A, and of agrimoniin to laevigatins B and C.View full abstractDownload PDF (732K) -
Tsuneatsu NAGAO, Hikaru OKABE, Kunihide MIHASHI, Tatsuo YAMAUCHI1989 Volume 37 Issue 4 Pages 925-929
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThree bisdesmosidic glucuronide saponins of quillaic acid, named dubiosides A, B and C, were isolated as their methyl esters from the tuber of Thladiantha dubia BUNGE(Cucurbitaceae). Their structures were elucidated on the basis of chemical and spectral evidence.All the dubiosides have a common prosapogenin structure, quillaic acid-3-O-β-D-galactopyranosyl(1→2)-β-D-glucuronopyranoside, and differ only in the structures of the 28-O-linked sugar moieties. Dubioside A is a 28-O-α-L-rhamnopyranosyl(1→2)-α-L-arabinopyranoside, dubioside B, a 28-O-β-D-xylopyranosyl(1→4)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranoside and dubioside C, a 28-O-β-D-xylopyranosyl(1→3)-β-D-xylopyranosyl(1→4)-α-L-rham-nopyranosyl(1→2)-α-L-arabinopyranoside.View full abstractDownload PDF (890K) -
Kazunari NAKAO, Yasumasa HAMADA, Takayuki SHIOIRI1989 Volume 37 Issue 4 Pages 930-932
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSAvellanins A and B (1 and 2), new pressor-active fungal metabolites from Hamigera avellanea, have been conveniently synthesized from methyl anthranilate. This synthetic study has established the absolute stereostructure of avellanin B (2). Coupling of methyl anthranilate with N-protected amino acid derivatives was best carried out by use of ((9-fluorenylmethyl)oxy)carbonyl (Fmoc)-amino acid chloride. Chain elongation for avellanins was accomplished with diethyl phosphorocyanidate, while cyclization was achieved with diphenyl phosphorazidate.View full abstractDownload PDF (613K) -
Nobuya KATAGIRI, Masatoshi HIROSE, Masayuki SATO, Chikara KANEKO1989 Volume 37 Issue 4 Pages 933-938
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS2, 4-Dioxo-1, 3-oxazine-5-carboxylic acid esters prepared by thermal reaction of 4-oxo-1, 3-dioxin-5-carboxylates with isocyanates were found to react with cyclopentadiene either in the presence or absence of suitable Lewis acid catalysts under quite mild conditions. Thus, reaction of methyl 3-substituted 2, 4-dioxo-1, 3-oxazine-5-carboxylates with cyclopentadiene either at room temperature or in the presence of a catalytic amount of titanium tetrachloride at -15°C gave the corresponding adducts in almost quantitative yield. The 5-phenyl derivative was converted to a carbocyclic C-uncleoside precursor through reductive retrograde aldol reaction (RRA reaction) as a key step. This titanium tetrachloride-catalyzed Diels-Alder reaction, when applied to l-8-phenylmenthyl 2, 4-dioxo-1, 3-oxazine-5-carboxylate, afforded the corresponding adduct in high diastereomeric excess (95% for the major endo adduct).View full abstractDownload PDF (966K) -
Hiroyuki ISHIBASHI, Suzumi HARADA, Motofumi OKADA, Midori SOMEKAWA, Ma ...1989 Volume 37 Issue 4 Pages 939-943
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS1, 3, 4, 5-Tetrahydro-3-methyl-2H-3-benzazepin-2-one derivatives were synthesize by acid-catalyzed cyclization of N-(2-arylethyl)-N-methyl-2-sulfinylacetamides. Some chemical transformations of the 2H-3-benzazepin-2-ones are also described.View full abstractDownload PDF (798K) -
Kazuhiko ICHINO, Hitoshi TANAKA, Kazuo ITO1989 Volume 37 Issue 4 Pages 944-947
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA new chalcone, linderachalcone, and two new flavanones, methyllinderatone and isolinderatone, were isolated from the leaves of Lindera umbellata THUNB. var. membranacea (MAXIM.) MOMIYAMA. Their structures were established by chemical and spectroscopic means.View full abstractDownload PDF (654K) -
Kaoru SENO, Sanji HAGISHITA1989 Volume 37 Issue 4 Pages 948-954
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSVarious stereoisomers based on the α- and ω-side chain ring junctions of 6, 6-dimethylbicyclo[3.1.1]heptane were synthesized. Their sodium salts 12, 18, 20, 30 and 37 were examined in vitro for their inhibitory activity toward aggregation of rabbit platelet-rich plasma and rat washed platelets. Their potency was very high and the partial agonist effect was small. The differences of the side chain ring junctions did not affect the activity very much. Homologication in the ω-side chain (as in 47) decreased the activity.View full abstractDownload PDF (1168K) -
Kazuta OGURI, Ching Kuei KUO, Hidetoshi YOSHIMURA1989 Volume 37 Issue 4 Pages 955-957
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSNormorphine-3- and -6-glucuronides were synthesized, and their analgesic effects were examined. Normorphine-3-glucuronide was obtained by condensation of normorphine with acetobromoglucuronate in the presence of sodium hydroxide in acetone. On the other hand, normorphine-6-glucuronide was synthesized by condensing N, O3-biscarboben-zoxynormorphine with acetobromoglucuronate in the presence of silver carbonate, and removing the protecting groups from the resultant reaction product by catalytic hydrogenation and solvolysis with sodium methoxide and barium hydroxide. The analgesic effect of normorphine-6-glucuronide (ED50 0.036 nmol/mice) was 125-fold more potent than that of normorphine in mice injected i.c.v. Normorphine-3-glucuronide was shown to be 37% effective at a dose of 2 nmol/mice, but induced convulsion at higher doses when given by i.c.v injection.View full abstractDownload PDF (506K) -
Minoru UCHIDA, Makoto KOMATSU, Seiji MORITA, Toshimi KANBE, Katsuya YA ...1989 Volume 37 Issue 4 Pages 958-961
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSMany 1-substituted 4-(5-tetrazolyl)thio-1-butanones were synthesized and tested for antiulcer activity against acetic acid-induced gastric ulcer in rats. These compounds were prepared by the reaction of 5-mercaptotetrazoles and 4-halogeno-1-butanones. Among them, 1-cyclohexyl-4-(1-phenyl-5-tetrazolyl)thio-1-butanone (VIIIp) was found to have the most potent activity. The structure-activity relationships are discussed.View full abstractDownload PDF (632K) -
Ryuichi IEMURA, Manabu HORI, Hiroshi OHTAKA1989 Volume 37 Issue 4 Pages 962-966
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe metabolites of 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1H-1, 4-diazepin-1-yl)-1H-benzimidazole difumarate (KG-2413), which has a potent H1-antihistaminic activity, were predicted on the basis of metabolic studies of related compounds and were synthesized to aid in identification of the actual metabolites and for examination of their antihistaminic activity. Among the twelve compounds prepared, nine compounds were actually found as the metabolites of KG-2413 in rat urine. The antihistaminic activities of these metabolites were found to be lower than that of KG-2413.View full abstractDownload PDF (842K) -
Ryuichi IEMURA, Hiroshi OHTAKA1989 Volume 37 Issue 4 Pages 967-972
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe quantitative structure-activity relationships (QSAR) of 2-(4-substituted-1-piperazinyl)benzimidazole derivatives for antihistaminic activity were examined. Taking into consideration the specific conformations of some derivatives, a significant correlation was obtained using Verloop's STERIMOL parameters B3 and L of the substituent at the 1-position of the benzimidazole nucleus. The results indicated that the derivatives having a substituent with a small breadth and an appropriate length at the 1-position showed potent activity. From the results, a model of the binding site is proposed. The QSAR of side effects (anticholinergic activity and central nervous system depressive effect) were also examined and the results showed that a sterically small substituent at the 1-position was required to decrease side effects.View full abstractDownload PDF (741K) -
Katsuhiro YAMASAKI, Hiroshi YOKOYAMA, Keiichi MIYANO, Yoshiki NUNOURA, ...1989 Volume 37 Issue 4 Pages 973-978
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSβ-Amylase activity was found in ginseng for the first time. β-Amylase was purified to apparent homogeneity on polyacrylamide slab gel from ginseng powder by dialysis of the crude extract and by column chromatography on diethylaminoethyl (DEAE)-Sephadex A-50, Sephadex G-100 and hydroxyapatite. The β-amylase was most active at pH 5.0 and 50°C. The molecular weight of the enzyme was estimated to be 63 kilodaltons (kDa) by both Sephadex G-100 column chromatography and sodium dodecyl sulfate gel electrophoresis. The isoelectric point of the enzyme was pH 5.3. Amino acid analysis indicated that the enzyme was composed of 512 amino acid residues. The content of neutral sugars was 8.5%, and no amino sugar was detected.View full abstractDownload PDF (956K) -
Shoji YAHARA, Tetsu OGATA, Reiko SAIJO, Ryoji KONISHI, Johji YAMAHARA, ...1989 Volume 37 Issue 4 Pages 979-987
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSTwenty-seven isoflavonoid monomer and dimer derivatives were obtained from the heartwood of Dalbergia odorifera T. CHEN (Leguminosae). The structure elucidation of twelve monomeric and five dimeric isoflavonoids is dealt with in this paper, affording novel examples of naturally occurring biisoflavonoids.View full abstractDownload PDF (1198K) -
Hiroko SHIMOMURA, Yutaka SASHIDA, Kazunori OGAWA1989 Volume 37 Issue 4 Pages 988-992
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSFrom the aerial parts of Ajuga ciliata var. villosior, nine new neo-clerodane diterpenes have been isolated. The structures of two acetyl derivatives of (12S)-6α, 12, 19-trihydroxy-1β-[(2S)-2-methylbutanoyloxy]-4, 18-epoxyneo-clerod-13(14)-en-15, 16-olide, three acetyl derivatives of (12S)-1β, 6α, 19-trihydroxy-12-[(2S)-2-metthylbutanoyloxy]-4, 18-epoxyneo-clerod-13(14)-en-15, 16-olide, three acetyl derivatives of (12S)-6α, 19-dihydroxy-12-[(2S)-2-mehylbutanoyl-oxy]-4, 18-epoxyneo-clerod-13(14)-en-15, 16-olide and methyl 6α-hydroxy-4α-methoxycarbonyl-18-norneo-clerod-13(14)-en-15, 16-olide were elucidated by spectroscopic methods and chemical correlation. In addition, a known neo-clerodane, ajugarin-IV, was isolated.View full abstractDownload PDF (729K) -
Taichi OHMOTO, Kazuo KOIKE, Katsuyoshi MITSUNAGA, Hiroshi FUKUDA, Keng ...1989 Volume 37 Issue 4 Pages 993-995
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA new quassinoid glucoside, javanicinoside A was isolated from the bark of Picrasma javanica (Simaroubaceae), and its structure was established on the basis of spectroscopic data and an X-ray crystal structure analysis.View full abstractDownload PDF (535K) -
Hiroko SHIMOMURA, Yutaka SASHIDA, Kazunori OGAWA1989 Volume 37 Issue 4 Pages 996-998
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSFrom the whole plants of Ajuga decumbens, four new neo-clerodane diterpenes, ajugamarins A2, G1, H1 and F4, and a previously known ajugamarin B2 have been isolated. The structures were elucidated on the basis of spectral data and chemical correlations.View full abstractDownload PDF (510K) -
Yoshiki KASHIWADA, Gen-ichiro NONAKA, Itsuo NISHIOKA1989 Volume 37 Issue 4 Pages 999-1004
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSMethods for simultaneous determination of phenolic constituents in rhubarbs have been established, making it possible to analyze almost all the phenolics, i.e., anthraquinones, anthrones, phenylbutanones, stilbenes, tannins, etc. Application of these methods to the evaluation of commercial rhubards has revealed that they can be classified into several groups on the basis of their chromatographic features.View full abstractDownload PDF (733K) -
Shigeru NARITA, Takayasu KITAGAWA1989 Volume 37 Issue 4 Pages 1005-1008
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS2-Phenylbenzotriazole derivatives with a COCH3 or NH2 group on the 2-phenyl ring were synthesized and found to be applicable as fluorescent hydrophobic probes. The fluorescence intensities of these compounds, which were intense in non-polar solvents, were dramatically quenched in polar solvents. In particular, 2-(4-acetylphenyl)-2H-benzotriazolyl-5-amine (7) showed a much higher ratio of the fluorescence intensity in the organic solvent to that in water (Fo/Fw) than 8-anilino-1-naphthalenesulfonate (ANS) : The Fo/Fw values of 7 were 470 for dioxane and 440 for acetone, while those of ANS were 100 for dioxane and 90 for acetone.We modified compound 7 to obtain water-soluble probes for use in drug-protein binding studies and examined the interaction of these probes with human serum albumin (HSA). All the compounds, which were practically non-fluorescent in the buffer solution, bound to HSA and fluoresced.View full abstractDownload PDF (518K) -
Shigeru NARITA, Takenobu TASAKI, Takayasu KITAGAWA1989 Volume 37 Issue 4 Pages 1009-1012
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA fluorescent probe applicable to protein binding measurement was developed. Several 2-phenylbenzotriazolyl-5-amine derivatives having an amino group on the 2-phenyl ring were synthesized. Their fluorescence characteristics and the binding affinity to α1-acid glycoprotein (α1-AGP)were investigated. They were practically non-fluorescent in aqueous solution, but were highly fluorescent in the presence of α1-AGP. This fluorescence was due to the binding of these compounds to α1-AGP. Of all the compounds synthesized, 7-chloro-2-(p-diethylaminophenyl)-2H-benzotriazolyl-5-amine (CDBA) bound to α1-AGP most strongly and was used as a fluorescent probe. The binding parameters of CDBA were estimated by the fluorometric titration method to be log K=6.18 and n=0.40. The fluorescence of CDBA in the α1-AGP solution was markedly quenched in the presence of basic drugs, indicating that these drugs competitively displace CDBA bound to α1-AGP. The binding constants of the basic drugs were calculated, based on the decrease of fluorescence intensity in the presence of the drug. The binding strength of the drugs tested ranged from 4.7 to 6.8 as log K value.View full abstractDownload PDF (594K) -
Tsunehiro KITAGAWA, Hideaki TANIMORI, Miwako SHIBATA, Kensei YOSHIDA, ...1989 Volume 37 Issue 4 Pages 1013-1018
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSAs a basic study to investigate suitable conditions to immunize rabbits with drug-immunogens, two highly sensitive and accurae enzyme immunoassays (EIAs) for specific antibody to viomycin (VM) and blasticidin S (BLS) were developed using the corresponding standard antibody, the solid-phase antigens, and enzyme-labeled goat anti-rabbit immunoglobulin G (IgG) antibody as immunological reagents. The accuracy of the assay results with these newly developed EIAs was demonstrated. The new EIAs as well as two previously developed EIAs, EIA for antibody specific to neocarzinostatin (NCS) and a sandwich EIA for rabbit IgG, were applied for analyses of the changes in contents of total and specific antibodies in rabbit antisera samples collected during immunizations with four antigens. Total IgG levels increased from 7.0-9.9 mg/ml to 30-50 mg/ml in all rabbits immunized under the same immunizing schedule, despite the use of four kinds of antigens. The highest level of specific antibodies, anti-BLS, anti-VM and anti-NCS, was 0.5 mg/ml in each case.View full abstractDownload PDF (856K) -
Toshihiro OHMORI, Kohji TAMURA, Kenji FUKUI, Gosei KAWANISHI, Masao MI ...1989 Volume 37 Issue 4 Pages 1019-1022
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA galactosaminoglycan moiety was obtained from an antitumor polysaccharide fraction (SN-C) isolated from Cordyceps ophioglossoides culture. SN-C was subjected to sonication, then a protein-bound galactosaminoglycan (CO-N) was isolated specifically by precipitation with 10% ammonium hydroxide.When given intraperitoneally to mice, CO-N inhibited the proliferation of sarcoma 180 cells inoculated into the peritoneal cavity and exhibited a marked life-prolonging effect against ascitic tumors such as Ehrlich carcinoma and IMC carcinoma. CO-N also showed an inhibitory effect against solid Ehrlich carcinoma when given intratumorally and significantly inhibited the growth of a syngeneic solid tumor (MM46 mammary carcinoma) upon intravenous administration at a low dose.CO-N showed a cytocidal effect against cultured cells of IMC and P388D1 in vitro. Flow cytometric analysis demonstrated that fluorescein isothiocyanate-CO-N binds to the surface of Ehrlich cells.View full abstractDownload PDF (665K) -
Nobuko SHIMIZU, Tamiko OHKURA, Hiroyuki AKITA, Takeshi OISHI, Yoichi I ...1989 Volume 37 Issue 4 Pages 1023-1027
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS4, (9S)- (2a) and 4, (9R)-dimethyl-(7S)-hydroxy-3-oxo-Δ4(10)-octalin (4a) were prepared in high optical purity (>99%ee) and in moderate yield by asymmetric reduction of the corresponding racemic diketone (±)-1 using yeasts. These compounds were used for formal total syntheses of C(8) oxygenated sesquiterpenoids such as (-)-artemisin, (-)-yomogin, (-)-3-oxodiplophyllin, β-elemenone, (+)-isotelekin, (+)-cuauhtemone and 4-epi-aubergenon.View full abstractDownload PDF (872K) -
Kohfuku KOHDA, Hiroshi KASAI, Takahiro OGAWA, Takayoshi SUZUKI, Yutaka ...1989 Volume 37 Issue 4 Pages 1028-1030
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSTreatment of calf thymus deoxyribonucleic acid (DNA) with bleomycin-Fe(II) at 0°C for 5 min resulted in the formation of 8-hydroxyguanine (8-OH-Gua) residues in DNA in a dose dependent manner, in addition to the formation of base propenal, a DNA-degradation product. The amount of 8-OH-Gua was about one-hundredth of that of base propenal. Treatment of cellular DNA with bleomycin did not result in any increase of 8-OH-Gus even under conditions of 100% cell killing.View full abstractDownload PDF (517K) -
Activation of Hepatic Microsomal Ca2+-Adenosine Triphosphatase by Calcium-Binding Protein RegucalcinMasayoshi YAMAGUCHI, Seiichi MORI1989 Volume 37 Issue 4 Pages 1031-1034
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe effect of regucalcin, a calcium-binding protein isolated from rat liver cytosol, on Ca2+-adenosine triphosphatase (ATPase) activity in hepatic microsomes was investigated. Mg2+-ATPase activity was clearly increased by the presence of 50 μM Ca2+. Regucalcin (1.0-4.0 μM) caused a remarkable elevation (about 3-fold) of Ca2+-ATPase activity. Also, Mg2+-ATPase activity was increased (about 1.6-fold) by the presence of regucalcin (2.0 and 4.0 μM). Guanosine-5'-O-(3-thiotriphosphate) (GTPrs; 10-5 and 10-4 M) and nicotinamide adenine dinucleotide phosphate oxidized form (NADP+; 10-5 to 10-3 M) or reduced form (NADPH; 10-4 and 10-3 M) significantly increased Ca2+-ATPase activity. These increases were not enhanced by the presence of regucalcin (2.0 μM). Of various metal ions, a comparatively low concentration of V5+ (10-5 M) or Cd2+ (10-6 M) significantly increased Ca2+-ATPase activity, while Hg2+, Zn2+, Cu2+ and Mn2+ did not have such an effect. Regucalcin (2.0 μM) did not enhance the effect of V5+ and Cd2+ on Ca2+-ATPase activity. The present finding, that regucalcin activates hepatic microsomal Ca2+-ATPase, suggests a cell physiological role of regucalcin as an activator in the microsomal Ca2+-pump activity. This action of regucalcin may not be influenced by other regulators.View full abstractDownload PDF (625K) -
Yoshitaka YANO, Kiyoshi YAMAOKA, Hisashi TANAKA1989 Volume 37 Issue 4 Pages 1035-1038
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA nonlinear curve fitting program MULTI(FILT) into which the fast inverse Laplace transform (FILT) is incorporated was developed on a microcomputer. FILT is an algorithm for the numerical inversion of Laplace-transformed equations (image equations) to generate the corresponding real time courses. The pharmacokinetic models can be defined in the form of Laplace-transformed equations as a subroutine in MULTI(FILT). MULTI(FILT) achieves the numerical inversion of the defined image equations according to FILT and the subsequent curve-fitting of the inverse-transformed time courses to the experimental data points to estimate the pharmacokinetic parameters by the nonlinear least-squares method. MULTI(FILT) has a function to impose constraints on the pharmacokinetic parameters. In order to verify the reliability of MULTI(FILT), the pharmacokinetic parameters estimated by MULTI(FILT) were compared with those by MULTI using 100 time courses which were artificially generated according to the Monte Carlo method, based on data for theophylline and bishydroxycoumarin. The estimated pharmacokinetic parameters by MULTI(FILT) agreed with those by MULTI. Thus, it is suggested that FILT, developed in the field of electronic technology, is also useful in the pharmacokinetic field.View full abstractDownload PDF (590K) -
Masanori SUGIURA, Youichiro NAITO, Yasunari YAMAURA, Chikara FUKAYA, K ...1989 Volume 37 Issue 4 Pages 1039-1043
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSVarious caffeic acid derivatives were synthesized, and their effects on 5-lipoxygenase (5-LO), 12-lipoxygenase (12-LO) and prostaglandin (PG) synthase activities were investigated. Among them, caffeic acid octyl amide (5) and 1-(3, 4-dihydroxyphenyl)-1-octen-3-one (11) showed very potent inhibitory activities toward 5-LO with IC50 values of 4.2×10-8 and 3.5×10-8 M, respectively. They were very selective inhibitors for 5-LO. Compound 11 showed noncompetitive inhibition, and the two adjacent hydroxy groups attached to the benzene ring, as well as the hydrophobic alkyl side chain, were required for its strong binding to 5-LO.View full abstractDownload PDF (908K) -
Yukihisa KURONO, Yasuhiro JINNO, Tomonari KUWAYAMA, Naomi SATO, Tamots ...1989 Volume 37 Issue 4 Pages 1044-1046
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSDiastereoisomers of oxazolam (2R-cis, 2R-trans, 2S-cis, and 2S-trans isomers) were resolved and assigned by high-performance liquid chromatography (HPLC). By means of HPLC the cis/trans isomerization rates of oxazolam in some organic solvents could be measured, although such rate measurements had previously been attempted only by an nuclear magnetic resonance (NMR) method and it was reported that in most organic solvents the isomerization was too fast to allow the rates to be measured. In some cases (depending on the lot number of the solvent), rapid isomerization was observed in chloroform-d (the ratio of cis isomer to trans isomer (2 : 3) did not change with time, that is, the isomerization was at equilibrium immediately after dissolution of oxazolam in the CDCI3). This fast isomerization was suggested to be catalyzed by an acid contaminant, since the iminium intermediate of oxazolam was detected in the reaction solution by fluorescence spectroscopy.View full abstractDownload PDF (522K) -
Eihei FUKUOKA, Midori MAKITA, Shigeo YAMAMURA1989 Volume 37 Issue 4 Pages 1047-1050
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSGlassy pharmaceuticals were prepared by cooling the melts and their state was confirmed by measuring the glass transition temperature (Tg) and the anomalous endothermic peak (heat capacity maximum) in the differential scanning calorimetry (DSC) curves. Glass formation was found for 20 pharmaceuticals (aspirin, phenobarbital, antipyrine and so on). The values of the ratio of Tg and melting temperature (Tm) of these pharmaceuticals lay between 0.59 and 0.84. Although the glassy indomethacin was very stable, remaining as a glass for 2 years at room temperature, glassy phenobarbital with the same Tg as glassy indomethacin was unstable, and devitrification occurred within a week. Thus the rate of crystallization of pulverized glassy phenobarbital was determined by the X-ray diffraction method. The crystallization of pulverized glassy phenobarbital proceeded rapidly and the degree of crystallinity reached a maximum of 75% after 24 h.Crystallization of glassy salicin was followed by means of DSC curves. It was revealed that stabilization by enthalpy relaxation occurred simultaneously with the crystallization in glassy salicin during standing.Binary glass systems of pharmaceuticals were prepared with the aim of improving the stability of the glass, and several thermal properties of binary glass systems were investigated.View full abstractDownload PDF (608K) -
Toshio SUZUKI, Etsuko SATO, Yasuyuki MATSUDA, Hitoshi TADA, Katsuo UNN ...1989 Volume 37 Issue 4 Pages 1051-1054
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSZein microspheres conjugated with antitumor drugs (mitomycinc (MMC), daunomycin hydrochloride (DM), peplomycin sulfate (PEP)) were prepared by using a dimethyl sulfoxide (DMSO)-H2O system. MMC with low solubility in H2O was easily entrapped by the standard procedure, whereas some modifications were required for moderately and highly soluble drugs such as DM and PEP.Colorimetric determination of the drugs in microspheres was easily achieved by use of the phenol-sulfuric acid method for drugs with sugar moieties in their molecules, such as DM and PEP, while a simple treatment of the microspheres with concentrated sulfuric acid was applied in the case of drugs having a chromophore in their molecules, such as DM and MMC.View full abstractDownload PDF (841K) -
Yoshinobu NAKAI, Keiji YAMAMOTO, Katsuhide TERADA, Toshio OGUCHI, Hiro ...1989 Volume 37 Issue 4 Pages 1055-1058
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSInclusion compounds were prepared by heating mixtures of a drug and α-cyclodextrin (α-CD) hydrate in a sealed container. Inclusion formation was studied as a function of heating temperature, water content of α-CD and drug properties, using powder X-ray diffraction, infrared spectroscopy, and differential scanning calorimetry. Drug molecules were included in α-CD molecules by heating above 80°C in ampules. Inclusion compounds were prepared with six different drugs. The rates of inclusion formation were well correlated with the vapor pressures of the drugs, that is, higher vapor pressure of drugs resulted in faster inclusion compound formation. It was revealed that the heating temperature, water content of α-CD, and vapor pressure of the drug are important parameters affecting the formation of inclusion compounds by the heating method.View full abstractDownload PDF (560K) -
Atsuya YOSHIDA, Masanobu YAMAMOTO, Tetsumi IRIE, Fumitoshi HIRAYAMA, K ...1989 Volume 37 Issue 4 Pages 1059-1063
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS3-Hydroxypropyl- and 2, 3-dihydroxypropyl-β-cyclodextrins (3-HP- and DHP-β-CyDs) with different degrees of substitution (D.S.) were prepared and their pharmaceutical properties were investigated. The aqueous solubility of 3-HP- and DHP-β-CyDs was much higher than that of the parent β-CyD and the dissolution of DHP-β-CyD in water was endothermic. The acid- and α-amylase-catalyzed hydrolysis rates of 3-HP- and DHP-β-CyDs were slower than those of the parent β-CyD. The hemolytic activity (human erythrocytes) and local irritancy (rabbit muscle) of DHP-β-CyD were considerably less than those of natural, methylated or other hydroxyalkylated β-CyDs, and decreased with increasing D.S. The ability of the hydroxyalkylated β-CyDs to remove cholesterol and proteins from human erythrocytes decreased with increasing D.S., and correlated well with their hemolytic activity. 3-HP-β-CyD was a more effective solubilizer for poorly water-soluble drugs than the parent β-CyD, and its stabilizing effect on chemically instable drugs was higher than that of the parent β-CyD. The above data suggest a considerable pharmaceutical potential of 3-HP- and DHP-β-CyDs as parenteral carriers.View full abstractDownload PDF (744K) -
Ken-ichi SUGIMORI, Shoichi MORI, Yoshiaki KAWASHIMA1989 Volume 37 Issue 4 Pages 1064-1067
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe role of a dry or wet binder in the prevention of capping within a tablet was evaluated by considering the binding strength of compacts and the residual die wall pressure during compression.Capping of bucetin tablets was not prevented by adding dried colloidal silica, which increased the binding strength and the residual pressure. However, the addition of dried low-substituted hydroxypropyl cellulose, which increased the binding strength but decreased the residual pressure, prevented the capping.The effect of addition methods of a low viscosity grade of hydroxypropyl cellulose and α-starch was also investigated for bucetin and ascorbic acid tablets. The compacts showed the greatest binding strength when the binders were added in a wet state. However, the residual die wall pressure did not depend on the addition method. These results suggest that the addition of a binder in the wet method is effective for the prevention of the capping.View full abstractDownload PDF (649K) -
Tsutomu MIMURA, Hiroshi NAKAJIMA, Kazutake TSUJIKAWA, Byoung Gag LEE, ...1989 Volume 37 Issue 4 Pages 1068-1070
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSFurther studies on the pharmacological effect of orally administered bis[2-(E-2-octenoyl-amino)ethyl] disulfide (compd. I-3) was examined by using several experimental models in vivo. Compound I-3 showed analgesic activity, inhibiting both acetic acid- and acetylcholine-induced writhings in mice. This compound also showed antipyretic activity against yeast-induced fever in rats, and significantly inhibited arachidonic acid-induced mortality in mice. However, it had no effect on serotonin-induced paw edema formation or platelet activating factor-acether-induced mortality in mice. The effects of compd. I-3 are suggested to be due to inhibition of prostaglandin biosynthesis.View full abstractDownload PDF (556K) -
Ken YASUKAWA, Michio TAKIDO, Mieko TAKEUCHI, Shigeki NAKAGAWA1989 Volume 37 Issue 4 Pages 1071-1073
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe induction of edema in the mouse ear has been established as a reliable in vivo assay for tumor promoters. Therefore, inhibitors of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema are most likely to be inhibitors of skin tumor promotion. Besides the application for this assay for the screening of compounds, it also allows comparison of the activities of groups of related compounds such as flavonoids. Results obtained in this way showed that the double bond at C-2 and C-3 of the flavonoid structure is a prerequisite for anti-tumor-promoting activity, and indicated that activity in this screening assay for inhibitors of TPA-induced ear edema reflects the anti-tumor-promoting effect in two-stage carcinogenesis.View full abstractDownload PDF (457K) -
Hidetoshi FUJIWARA, Akira KATO, Ichizo OKABAYASHI1989 Volume 37 Issue 4 Pages 1074-1077
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe mass spectra (MS) of 9-(1H-benzimidazol-2-ylmethyl)-9H-xanthene (1), 9-(1H-benzimidazol-2-ylmethyl)-9H-thioxanthene derivatives (2), and the 10-oxide (3) and 10, 10-dioxide (4) derivatives of 2 were measured by electron ionization.The MS of 1 and 2 showed a peak corresponding to the loss of the substituent at the 9-position and a peak at m/z 152. The MS of 3 showed peaks corresponding to the loss of OH radical, the 1H-benzimidazol-2-ylmethyl group at the 9-position, and the oxygen atom. The MS of 4 showed peaks corresponding to the loss of OH radical, the 1H-benzimidazol-2-ylmethyl group at the 9-position, and SO2.View full abstractDownload PDF (509K) -
Yuji MORI, Miki KUHARA, Makoto SUZUKI1989 Volume 37 Issue 4 Pages 1078-1079
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS(1R, 3R, 5S)-1, 3-Dimethyl-2, 9-dioxabicyclo[3.3.1]nonane (1), a host-specific substance of ambrosia beetle, has been synthesized stereoselectively based on a highly syn-selective 1, 3-asymmetric reduction of the β-alkoxy ketone (5) using lithium aluminum hydride-lithium iodide.View full abstractDownload PDF (440K) -
Jiro HORIUCHI, Kazuo SUZUKI, Eiki SHITARA, Ryuji NIWA, Tetsuzo KATO1989 Volume 37 Issue 4 Pages 1080-1084
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe reaction of thioureas (9) with 2-chloromethylpyridine hydrochloride (5), 3-chloromethylpyridine hydrochloride (6), 2-chloromethylquinoline hydrochloride (7), and 5-chloromethyl-4-methylimidazole hydrochloride (8) geve the isothiourea dihydrochlorides (10-13).View full abstractDownload PDF (653K) -
Mitsuhiro TAKESHITA, Takumi SATO1989 Volume 37 Issue 4 Pages 1085-1086
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSReduction of 1-phenyl-1, 2-propanedione with baker's yeast afforded (1R, 2S)-1-phenyl-1, 2-propanediol in high chemical and optical yield. (1R, 2S)-, (1R, 2R)- and (1S, 2S)-1, 2-propanediols were also prepared via (1R)- or (2S)-α-ketols, which were obtained as intermediates of the above reaction.View full abstractDownload PDF (483K) -
Nobuo IKOTA, Akira HANAKI1989 Volume 37 Issue 4 Pages 1087-1089
Published: April 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS(2S, 3S, 4S)-4-Amino-2, 3-dihydroxyhexanedioic acid derivatives (11 and 12) were synthesized from an (R)-pyroglutamic acid derivative (3) by cis-dihydroxylation of the α, β-unsaturated lactam (4) as the key reaction.View full abstractDownload PDF (573K)