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SABURO SHIMABAYASHI, OSAMU KUSADA, MASAYUKI NAKAGAKI
1987 Volume 35 Issue 6 Pages
2163-2170
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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The hydrolysis of diphosphate ion (pyrophosphate ion, PPi) to orthophosphate ion (Pi) in the presence of Ca
2+ in aqueous systems were examined. The systems studied were (1) K
4P
2P
7+CaCl
2 with/without KOH, (2) K
4P
2O
7 +Ca (OH)
2, (3) aqueous suspension of the precipitate isolated from the mother solution immediately after mixing of K
4P
2O
7 and CaCl
2, and (4) K
4P
2O
7 in an aqueous suspension of Ca
2P
2O
7. It was found that the gradual release of Ca
2+ to the aqueous phase from the Ca
2+-reservoir (
i.e., Ca (OH)
2 formed (system 1) or added (system 2)) is effective for the hydrolysis of PPi. When the temporary precipitate containing PPi was suspended in the aqueous phase (system 3), the hydrolysis of PPi was delayed because re-dissolution of the precipitate was necessary prior to the hydrolysis. The result in system 4 suggested that the hydrolysis reaction occurs on the surface of Ca
2P
2O
7. These results are discussed in connection with a possible physicochemical mechanism of deposition of mixed crystals (calcium diphosphate and calcium orthophosphate) in the human body, causing mixed crystal deposition disease.
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SABURO SHIMABAYASHI, HIDEJI TANAKA, MASAYUKI NAKAGAKI
1987 Volume 35 Issue 6 Pages
2171-2176
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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Concentrations of phosphate ion ([Pi]
f) and calcium ion ([Ca
2+]
f) liberated from the surface of hydroxyapatite (Ca
10 (PO
4)
6(OH)
2; HAP) during the adsorption of dodecyl sulfate ion (DS
-) onto HAP were determined at various concentrations of added salt (NaCl or Na
2HPO
4). The effects of added salt on the relationships among [Pi]
f, [Ca
2+]f, the concentration of DS
-([DS
-]
f), and the adsorbed amount of DS
- (
XDS-) are discussed. The amount of
XDS- increased monotonously with the concentration of NaCl added ([NaCl]
i). However, the equilibrium concentrations of phosphate ion (Pi) and calcium ion (Ca
2+) changed in a complex manner with [NaCl]
i. It was concluded that ions on the surface of HAP were partly ion-exchanged with those of sodium dodecyl sulfate and NaCl, and that Ca
2+ and Na
+ were bound competitively as counter-ions to DS
- micelles. On the other hand, when Na
2HPO
4 was added to the solution, added Pi (
i.e., one of the lattice ions for HAP) had a drastic effect on
XDS- and [Ca
2+]
f. The adsorbed amount of DS
- decreased with increasing concentration of added Na
2HPO
4 owing to competitive adsorption between DS
- and added Pi. The equilibrium concentration of Ca
2+, [Ca
2+]
f, decreased for two reasons. First, adsorbed Pi inhibits the release of Ca
2+ from the surface of HAP by virtue of the electrostatic attractive force. Secondly, the excess Pi remaining in the solution prevents Ca
2+-release from the surface of HAP since the solubility product for HAP must remain constant.
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TOSHIKI MUTO, HIROAKI MASUMORI, TOSHIAKI MIURA, MICHIYA KIMURA
1987 Volume 35 Issue 6 Pages
2177-2183
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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The mode of oxygenation by
meso-tetraphenylporphinatoiron (III) chloride (Fe (III) TPPCl) -peroxide systems was characterized by using
cis-stilbene (1) and cholesteryl acetate (3) as substrates. The stereoselectivity of epoxidation of 1 by the Fe (III) TPPCl-
tert-butyl hydroperoxide (
tBuOOH) system depended on the concentration of Fe (III) TPPCl; the reaction was nonstereoselective at 0.1 mM Fe (III) TPPCl but stereoselective at 10 mm Fe (III) TPPC1. In the reaction of 3 with the same system, both allylic oxidation and epoxidation proceeded. However, the epoxidation wasβ-selective independently of the concentration of Fe (III) TPPCl. Thus,
tBuOOH is assumed to decompose by a radical chain reaction mechanism to give
tert-butylperoxyl radical (
tBuOO·) and
tert-butyloxyl radical (
tBuO·) at 0.1 mM Fe (III) TPPCl. At 10 mm Fe (III) TPPCl, on the other hand, the O-O bond in the Fe (III) TPPCl-
tBuOOH complex may cleave in both a homolytic manner (quasi-Fenton mechanism) and a heterolytic one (ferryl ion mechanism). The former leads to
tBuO·as the active oxygen species responsible for the allylic oxidation of 3 and the latter to ferryl ion (Fe-O·) as that responsible for the stereoselective epoxidation of 1 and β-epoxidation of 3.
In the reaction with the Fe (III) TPPCl-
m-chloroperbenzoic acid (MCPBA) system at-30°Cin the presence of γ-collidine, β-selective epoxidation of 3 proceeded predominantly while 1 was epoxidized stereoselectively. The stereoselectivities of these epoxidations closely resemble those with the Fe (III) TPPCl-iodosylbenzene system, which is known to give the ferryl ion. These results suggest that the O-O bond in the Fe (III) TPPCl-MCPBA complex cleaves mainly in the heterolytic manner (ferryl ion mechanism).
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YUJI OIKAWA, TATSUYOSHI TANAKA, KIYOSHI HORITA, ICHIO NODA, NORIYUKI N ...
1987 Volume 35 Issue 6 Pages
2184-2195
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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For the highly stereoselective synthesis of methynolide (2), the aglycon of the 12-membered macrolide antibiotic methymycin (1), a Prelog-Djerassi lactone-type chiral intermediate (7a) bearing four chiral centers corresponding to the C-2, C-3, C-4, and C-6 positions was synthesized from D-glucose. In this synthesis, several stereocontrolled reactions such as hydroboration, catalytic hydrogenation,
etc. were successfully applied. The utility of the 4-methoxybenzyl protecting group was also demonstrated.
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YUJI OIKAWA, TATSUYOSHI TANAKA, TATSUO HAMADA, OSAMU YONEMITSU
1987 Volume 35 Issue 6 Pages
2196-2202
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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A highly stereoselective synthesis of the seco-acid (3) of methynolide (1), the aglycon of the 12-membered macrolide methymycin was carried out, starting from D-glucose via the Wittig-Horner coupling of the two segments i (4) (C-9-C-13) and ii (5) (C-1-C-8), which were synthesized by the use of
p-methoxybenzyl and
p-methoxybenzylidene acetal protecting groups for hydroxy functions.
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TATSUYOSHI TANAKA, YUJI OIKAWA, NORIYUKI NAKAJIMA, TATSUO HAMADA, OSAM ...
1987 Volume 35 Issue 6 Pages
2203-2208
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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Methynolide (1), the aglycon of the 12-membered macrolide antibiotic methymycin, was synthesized highly stereoselectively and efficiently from D-glucose via two segments i (3 : C-9-C-13) and ii (4 : C-1-C-8). Esterification of the two segments proceeded smoothly by Yamaguchi's method. When the resulting ester (10) was treated with potassium carbonate in toluene in the presence of 18-crown-6 at 80 °C under Nicolaou's conditions, the intramolecular Wittig-Horner reaction occurred very smoothly, and the 12-membered cyclic enone (11) was isolated in excellent yield. Finally, silyl and benzyl protecting groups were removed with fluoride anion and 2, 3-dichloro-5, 6-dicyanobenzoquinone, respectively, to afford methynolide (1) in excellent yield. The overall stereoselectivity for the construction of four new chiral centers was very high (89%).
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TATSUYOSHI TANAKA, YUJI OIKAWA, TATSUO HAMADA, OSAMU YONEMITSU
1987 Volume 35 Issue 6 Pages
2209-2218
Published: June 25, 1987
Released on J-STAGE: February 12, 2010
JOURNAL
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In order to synthesize tylonolide, the aglycon of the 16-membered macrolide antibiotic tylosin, a Prelog-Djerassi lactone-type compound (4) corresponding to the C-1-C-9 segment was synthesized from D-glucose. Benzyl-type protecting groups for hydroxy functions, such as benzyl, 4-methoxybenzyl, and 3, 4-dimethoxybenzyl groups, as well as some cyclic and acyclic stereocontrolled reactions, such as hydroboration, catalytic hydrogenation, and Grignard reaction, were successfully employed.
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TATSUYOSHI TANAKA, YUJI OIKAWA, TATSUO HAMADA, OSAMU YONEMITSU
1987 Volume 35 Issue 6 Pages
2219-2227
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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Tylonolide, was synthesized from D-glucose
via coupling and cyclization of two segments i (2) (C-11-C-17) and ii (3) (C-1-C-10), which were synthesized from diacetoneglucose. A Prelog-Djerassi lactone-type compound was an intermediate in the synthesis of the latter segment. Esterification of the two segments by Yamaguchi's method followed by macrocyclization by use of the Wittig-Horner reaction gave the 16-membered cyclic enone, whose protecting groups were removed to afford tylonolide. In this total synthesis, 4-methoxybenzyl and 3, 4-dimethoxybenzyl protecting groups played an important role.
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NORIYUKI NAKAJIMA, TATSUYOSHI TANAKA, TATSUO HAMADA, YUJI OIKAWA, OSAM ...
1987 Volume 35 Issue 6 Pages
2228-2237
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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The first total synthesis of pikronolide, the aglycon of pikromycin, isolated as the first macrolide antibiotic, is described. Two segments i (5 : C-1-C-10) and ii (6 : C-11-C-15) were synthesized highly stereoselectively from D-glucose and coupled by Yamaguchi's method to give the ester (17), which was subjected to macrocyclization by means of the intramolecular Wittig-Horner reaction developed by Nicolaou, and the 14-membered cyclic enone (18) was isolated in excellent yield. Removal of protecting groups and Swern oxidation gave pikronolide (2). In this synthesis, 3, 4-dimethoxybenzyl, 4-methoxybenzyl, and benzyl protecting group for hydroxy function played a crucial role.
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HIROYUKI MIZUTA, SHUNSUKE NARUTO, HARUKI NISHIMURA
1987 Volume 35 Issue 6 Pages
2238-2242
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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Hydrazinolysis of 5, 6-dihydro-2, 3, 10-trimethoxy-13-methyl-9- (2-phthalimidoethoxy) dibenzo [a, g] quinolizinium bromide (2) and 7-methoxy-1- (3, 4-dimethoxybenzyl) -2-methyl-6- (2-phthalimidoethoxy) isoquinolinium bromide (17) gave 5, 6-dihydro-9- (2-hydroxyethyl) amino-2, 3, 10-trimethoxy-13-methyldibenzo [a, g] quinolizinium bromide (3) and 6- (2-hydroxyethyl) amino-7-methoxy-1- (3, 4-dimethoxybenzyl) -2-methylisoquinolinium bromide (18), respectively,
via the Smiles rearrangement. An additional example of these rearrangements is also described.
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HIROAKI YAMAZAKI, HIDENORI HARADA, KENICHI MATSUZAKI, KIMITOMO YOSHIOK ...
1987 Volume 35 Issue 6 Pages
2243-2253
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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Reactions of 5-methyl-2
H-1, 4-thiazin-3 (4
H) -one (4) with various
N-acylpyridinium salts (7a-g) led to (
N-acyldihydropyridyl) thiazinones (5a-g), oxidation of which yielded a new class of pyridylthiazinones (6a-g). These reactions were applied to the synthesis of other azaarylthiazinones. Some of these azaarylthiazinones, particularly 6- (4-pyridyl) thiazinones (6a, 14a and 14b) showed positive inotropic activity with little chronotropic effect on guinea pig left atria.
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HARUHIRO FUJIMOTO, HIDEMI HAGIWARA, KUMIKO SUZUKI, MIKIO YAMAZAKI
1987 Volume 35 Issue 6 Pages
2254-2260
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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Four new triterpene glycosides, hebevinosides VI, VII, VIII, and IX, whose common aglycone is 3β, 7β, 16β-trihydroxycucurbita-5, 24-diene (hydroxyhebevinogenin), have been isolated from the acetone extract of a poisonous mushroom,
Hebeloma vinosophyllum, and deduced to have the structures of 3β, 7β, 16β-trihydroxycucurbita-5, 24-diene-3-
Ο-β-D-xylopyranoside-16-O-β-D-glucopyranoside, 3β, 7β, 16β-trihydroxycucurbita-5, 24-diene-3-
Ο-β-D-xylopyranoside-16-
Ο- (4, 6-di-
Ο-acetyl) -β-D-glucopyranoside, 3β, 7β, 16β-trihydroxycucurbita-5, 24-diene-3-
Ο- (4-
Ο-acetyl) -β-D-xylopyranoside-16-
Ο- (4, 6-di-
Ο-acetyl) -β-D-glucopyranoside, and 3β, 7β, 16β-trihydroxycucurbita-3-
Ο-β-D-xylopyranoside, respectively. Two new glycosides, hebevinosides X and XI, whose common aglycone is 3β, 16, β-dihydroxy-7β-methoxycucurbita-5, 24-diene (methoxyhebevinogenin), have also been isolated from the aqueous methanolic extract of the mushroom in addition to hebevinosides I, II, III, IV, and V previously reported, and deduced to be 3β, 16β-dihydroxy-7β-methoxycucurbita-5, 24-diene-3-
Ο-β-D-xylopyranoside-16-
Ο-β-D-glucopyranoside and 3β, 16β-dihydroxy-7β-methoxycucurbita-5, 24-diene-3-
Ο-β-D-xylopyranoside-16-
Ο- (4, 6-di-
Ο-acetyl) -β-D-glucopyranoside, respectively.
Among these eleven hebevinosides, I, IV, V, X, and XI, whose common aglycone is methoxyhebevinogenin, have been proved to be artifacts formed from the genuine metabolites III, IX, II, VI, and VII, whose common aglycone is hydroxyhebevinogenin, during extraction of the mushroom with aqueous methanol, respectively, and VIII, whose aglycone is hydroxyhebevinogenin, has also been proved to be a genuine metabolite of this mushroom.
The relationship between the structure and toxicity of hebevinosides was also investigated.
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SATOSHI HIBINO, EIICHI SUGINO, TOSHIHARU YAMOCHI, MASUKI KUWATA, HIROK ...
1987 Volume 35 Issue 6 Pages
2261-2265
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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Nitramarine (1), which possesses a β-carboline nucleus, was synthesized by two routes. First, we applied an intramolecular thermal cyclization of the 1-azahexatrienesystem in heteroaromatics such as 2. Although no intermediate (9 or 10) could be isolated, heating of 7 in toluene or of 8 in odichlorobenzene in the presence of hydroxylamine gave nitramarine (1) or its derivative (11), respectively. On the other hand, the Pictet?Spengler reaction between (±) -tryptophan ethyl ester (12) and 2-quinoline carbaldehyde (13) gave nitramarine carboxylic acid ethyl ester (11). Subsequent hydrolysis followed by decarboxylation gave 1. Nitramarine carboxylic acid (15) and carboxamide (16) were found to prolong the sleeping time of mice.
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YOSHIHISA MORIMOTO, YOSHIYASU TERAO, KAZUO ACHIWA
1987 Volume 35 Issue 6 Pages
2266-2271
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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The asymmetric hydrolysis of five-membered cyclic diesters was carried out by using pig liver esterase (PLE) as a catalyst. The absolute configurations of the resulting half esters and recovered diesters were established and the stereospecificity of PLE action in such systems was revealed.
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TAICHI OHMOTO, KEIJI IKEDA, SACHIYO NOMURA, MASARU SHIMIZU, SACHI SAIT ...
1987 Volume 35 Issue 6 Pages
2272-2279
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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Two new sesquiterpenes, 6α-hydroxyeudesm-4 (15) -ene-9β-
Ο-anisate (3) and 1β-hydroxyeudesma-4, 11 (13) -dien-12-oic acid (4), were isolated, together with damsinic acid (1) and β, 6α-dihydroxyeudesm-4 (15) -ene (2), from Ambrosia elatior (Compositae). The structures were determined by chemical and spectroscopic methods.
1H-
1H,
1H-
13C and long-range
1H-
13C two dimensional chemical correlation nuclear magnetic resonance analyses were carried out to confirm the structure of 4.
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TERUYUKI MIYAMOTO, HIROSHI EGAWA, JUN-ICHI MATSUMOTO
1987 Volume 35 Issue 6 Pages
2280-2285
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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An alternative synthesis of enoxacin, a 1, 8-naphthyridine antibacterial agent, was developed. The present method involves 1, 8-naphthyridine ring construction by the Dieckmann type cyclization of ethyl 5-fluoronicotinate having a 2-ethoxycarbonylethylamino moiety at C-2. This nicotinate was prepared in 7 steps from ethyl fluoroacetate via ethyl 2, 6-dichloro-5-fluoronicotinate.
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KAZUO KOYAMA, KOICHI KOJIMA
1987 Volume 35 Issue 6 Pages
2286-2291
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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A new isocarbacyclin analogue (1a), containing a bicyclo [3.2.1] octane ring system, has been synthesized by means of a regioselective rearrangement of the cyclopropyl carbinol (8) to the homoallyl bromide (9) with hydrobromic acid. Compound 1a showed very weak inhibitory activity against platelet aggregation.
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HIROMU KAWAKUBO, KENTARO FUKUZAKI, TAKANORI SONE
1987 Volume 35 Issue 6 Pages
2292-2299
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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Various 1-or 3- (substituted 3-amino) indazoles with anti-inflammatory effects were synthesized by means of three methods, as follows. 1) Reactions of 3-aminoindazole (1) with acrylamides (2a and 2b) gave amide derivatives (3a and 3b) having a carbamoylethylamino group at the 3-position of 3a and 3b. The amide derivatives (3a and 3b) were converted to thioamide derivatives (4a and 4b) by treatment with P
2S
5. Electrode reduction of 4a and 4b gave 3- (substituted 3-amino) indazoles (5a and 5b). 2) The reaction of 1 with aminoalkyl. halides (6c-r) gave 3- (substituted 3-amino) indazoles (5c-r) and 1- (substituted 3-amino) indazoles (7c-r) in a ratio of 3 : 1. 3) The reaction of 1 with phthalic anhydride (8) gave 3-phthalimidoindazole (9). Compound 9 was allowed to react with aminoalkyl halides (6o-r) to give 1-substituted derivatives (10s-z) of 9, Reactions of 10a-z with hydrazine hydrate gave 1- (substituted 3-amino) indazole derivatives (5s-z).
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KAZUTAKE SHIMADA, YOSHIHIRO SATO, TOSHIO NAMBARA
1987 Volume 35 Issue 6 Pages
2300-2304
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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The occurrence of marinobufagin 3-succinyl-L-arginine and 3-glutaryl-L-arginine esters, and telocinobufagin 3-glutaryl-L-arginine ester, together with seven known bufogenins, in the skin of
Bufo bankorensis BORBOUR, is reported. The structures were elucidated by degradative means and/or direct comparison with authentic samples. These compounds were assayed for inhibitory activity towards guinea pig heart Na
+, K
+-adenosine triphosphatase.
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YASUMITSU TAMURA, HIROKAZU ANNOURA, HIROSHI KONDO, MASAHIRO FUJI, TAKA ...
1987 Volume 35 Issue 6 Pages
2305-2313
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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Four chiral cyclic a-keto acetals (3a-d) were prepared through transacetalization of the α-hydroxydimethyl acetals [1 (
n = 1,
n = 2)] with (-) - (2
S, 3
S) -1, 4-dimethoxy-2, 3-butanediol or (-) - (2
R, 3
R) -2, 3-butanediol and reacted with organometallic reagents (Grignard reagents and organo-lithium reagents). The reactions of the α-keto acetals (3a, 3b) derived from 1 and (-) - (2
S, 3
S) -1, 4-dimethoxy-2, 3-butanediol with Grignard reagents proceeded in a highly diastereoselective manner.
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MASARU KOBAYASHI, TAKASHI ISHIZAKA, NORIKO MIURA, HIROSHI MITSUHASHI
1987 Volume 35 Issue 6 Pages
2314-2318
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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Nine cembrane-type diterpenes were isolated from the lipid extract of the soft coral,
Sinularia mayi. Of these, seven α-methylene-γ-lactone derivatives (1-7) had been previously isolated from various soft corals. The structures of the two new cembrane diols, sinulariol A (8a) and sinulariol B (9), were determined by means of spectroscopic analyses, and compound 9 was chemically correlated with nephthenol (11) whose absolute configuration is known. Compounds 8a and 9 are plausible precursors to the cembrane lactones found in various soft corals.
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MASAKUNI KORI, KATSUMI ITOH, HIROSADA SUGIHARA
1987 Volume 35 Issue 6 Pages
2319-2326
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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A chemoenzymatic synthesis of the new angiotensin converting enzyme inhibitor CV-5975 (1) is described. The optically active key intermediate for the synthesis of 1, ethyl (
R) -6- (1-benzyloxycarbonyl-4-piperidyl) -2-hydroxyhexanoate ((
R) -4), was prepared by kinetic resolution of the racemic α-hydroxyester ((
RS) -4) with a lipase and also by asymmetric reduction of the α-oxoester (3) with baker's yeast. The enantiomeric excess (ee) of the α-hydroxyester ((
R) -4) produced by these enzymatic procedures exceeded 60%. This optically active alcohol ((
R) -4) was converted to its mesylate ((
R) -5), which was then subjected to
SN2 reaction with the aminobenzothiazepine derivative (2) followed by deprotection to yield 1.
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NAOKI SAKURA, MIWAKO NISHIJIMA, YOSHIKI UCHIDA, TETSUHIRO TANI, TADASH ...
1987 Volume 35 Issue 6 Pages
2327-2333
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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Synthesis of peptides related to hydra head activator (HA; pGlu-Pro-Pro-Gly-Gly-Ser-Lys-Val-Ile-Leu-Phe-OH) was performed by the solution method. The analogs synthesized were Tyr
11-HA, des-Phe
11-HA, Arg
1-HA and Phe
5-HA. Antisera were prepared by immunizing three rabbits with the synthetic HA. Two anti-HA-antisera with sufficient titer were obtained. An HA-radioimmunoassay system, developed by using an antiserum (ASH-04) and
125I-Tyr
11-HA as a tracer, was found to be sensitive and specific to HA.
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TETSUJI KAMETANI, TADASHI KATOH, MASAYOSHI TSUBUKI, TOSHIO HONDA
1987 Volume 35 Issue 6 Pages
2334-2338
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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26, 27-Bisnorbrassinolide was synthesized from pregnenolone by employing a stereoselective reduction of the 5-ylidenetetronate derivative as a key step.
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NOBUTAKA FUJII, AKIRA OTAKA, SUSUMU FUNAKOSHI, KIYOSHI BESSHO, TOSHIHI ...
1987 Volume 35 Issue 6 Pages
2339-2347
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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Thallium (III) trifluoroacetate, a mild oxidant with a soft-acid character, was found to cleave various S-protecting groups of cysteine in trifluoroacetic acid, with spontaneous formation of cystine. Except for unmasked Trp and Met, other amino acids, including His and Tyr, remained intact in the presence of this oxidant. The usefulness of this oxidant for intramolecular disulfide bond-forming reactions was demonstrated by direct conversion of three model S-protected cysteine-peptides into cystine-peptides,
i.e., oxytocin, urotensin II and human calcitonin generelated peptide.
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MIYOJI HANAOKA, HIROSHI YAMAGISHI, MARI MARUTANI, CHISATO MUKAI
1987 Volume 35 Issue 6 Pages
2348-2354
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
JOURNAL
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An efficient synthesis of nitidine (1a).and fagaronine (1c), antitumor 2, 3, 8, 9-tetraoxygenated benzo [c] phenanthridine alkaloids, has been achieved
via regioselective C
6-N bond cleavage, followed by consecutive oxy-functionalization and recyclization between the C
6 and C
13 positions of the starting protoberberines, pseudoberberine (3a) and
O-benzyldehydrodiscretine (3b), respectively.
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TOZO FUJII, MASASHI OHBA, HIROSHI HATAKEYAMA
1987 Volume 35 Issue 6 Pages
2355-2359
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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The chirál synthesis of (-) -9-demethyltubulosine [(-) -1] has been achieved for the first time
via a “cincholoipon-incorporating route, ” which started from cincholoipon ethyl ester [(+) -7] and passed through the intermediates (-) -8, (-) -9, (+) -10, and (+) -11. As a result, the absolute configuration of the
Alangium vitiense alkaloid 9-demethyltubulosine has been unequivocally established to be that represented by formula (-) -1.
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MASASHI TOMODA, ME ICHIKAWA
1987 Volume 35 Issue 6 Pages
2360-2365
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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A representative mucilage, named Hibiscus-mucilage SF, was isolated from the white flower buds of
Hibiscus syriacus L. It was homogeneous on electrophoresis and gel chromatography. Its intrinsic viscosity value in aqueous solution was 26.0. It is mainly composed of partially acetylated acidic polysaccharide of molecular weight 1050000, and is composed of L-rhamnose : D-galactose : D-galacturonic acid : D-glucuronic acid in the molar ratio of 36 : 36 : 33 : 22. Methylation analysis of both the mucilage and the carboxyl-reduced derivative, and partial hydrolysis studies enabled elucidation of the structural features.
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SANTIAGO GUBERT, CELIA PALACIN, AURELIO SACRISTÁN, JOSÉ ...
1987 Volume 35 Issue 6 Pages
2366-2372
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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Nine esters of hetacillin or hetamoxicillin were synthesized as ampicillin and amoxicillin derivatives with the aim of obtaining improved plasma levels after oral administration. Out of these esters, which are devoid of apparent toxic effects, the benzyloxymethyl ester of hetacillin (FI-5204) gave the best result and was chosen for subsequent studies.
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JUN-ICHI YAMASHITA, SETSUO TAKEDA, HIROSHI MATSUMOTO, NORIO UNEMI, MIT ...
1987 Volume 35 Issue 6 Pages
2373-2381
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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Various
O-alkoxyalkyl derivatives of 2'-deoxy-5-trifluoromethyluridine (F
3Thd) were synthesized, and the antitumor activities of the compounds against sarcoma 180 were examined by oral administration to mice. Among the formal-type derivatives, 3', 5'-di-
O-ethoxymethyl (3), 3', 5'-di-
O-benzyloxymethyl (12), 5'-
O-benzyloxymethyl (13) and 3'-
O-benzyloxymethyl (14) compounds showed high activities, which were six-fold higher than that of F
3Thd itself. Since acetal-type derivatives were unstable under acidic conditions, antitumor testing of the compounds was also carried out with co-administration of sodium bicarbonate. 5'-
O- (1-Ethoxypropyl) -F
3Thd (25) and 5'-
O- (1-benzyloxypropyl) -F
3Thd (37) showed the highest activities among the acetal-type derivatives, but the ED
50 values of the compounds were not lower than those of effective formal-type compounds.
These
O-alkoxyalkyl derivatives of F
3Thd are resistant to degradation by thymidine phosphorylase and are activated by microsomal drug-metabolizing enzymes after absorption.
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TAKETOSHI KOMORI, KATSUMI ASANO, YASUTO SASAKI, HIROMI HANAI, RUMI SEO ...
1987 Volume 35 Issue 6 Pages
2382-2387
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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N-Mercaptoalkanoyl derivatives of sulfur-containing amino acids were synthesized and examined for inhibitory effects on angiotensin I converting enzyme (ACE) extracted from rabbit lung. Inhibition of ACE was determined by means of a spectrometric assay with hippuryl-L-histidyl-L-leucine as a substrate. Among the synthesized sulfur-containing compounds,
N- (2-benzyl-3-mercaptopropanoyl) -S-methyl-L-cysteine (13a) and
N- (2-benzyl-3-mercaptopropanoyl) -
S-ethyl-L-cysteine (13c) showed the most potent inhibitory effects on ACE activity. The IC
50 values of 13a and 13c on ACE activity were 0.028 and 0.020 μM, respectively.
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TAKETOSHI KOMORI, KATSUMI ASANO, YASUTO SASAKI, HIROMI HANAI, SHIRO MO ...
1987 Volume 35 Issue 6 Pages
2388-2393
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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N-Mercaptoalkanoyl derivatives of sulfur-containing amino acids were synthesized as candidate angiotensin I converting enzyme (ACE) inhibitors. Among them,
N-[3-mercapto-2- (4-methoxybenzyl) propanoyl] -S-ethyl-L-cysteine (5d) was found to be the most potent inhibitor of ACE, with an IC
50 value of 0.045μ
M. The maximum hypotensive effect of this compound was almost equal to that of captopril in anesthetized rats.
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HIROYUKI NATE, KENJI MATSUKI, AKIRA TSUNASHIMA, HISAO OHTSUKA, YASUO S ...
1987 Volume 35 Issue 6 Pages
2394-2411
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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A large number of 2- (phenylpiperazinoalkoxyphenyl) thiazolidine-3-thiocarboxamides and the corresponding carboxamides (II) were synthesized and tested for inotropic activity in anesthetized dogs. Compounds II were prepared from a hydroxybenzaldehyde (III) through the intermediates (IV, V, and X). Structure-activity relationships (SAR) were investigated by varying the structural parameters. Transposition of the piperazinoalkoxyl group to the
meta or
para position from the
ortho position caused a marked fall in activity. Conversion of the thiocarboxamido to a carboxamido group caused a marked increase in activity. This tendency was generally observed in this series of compounds and constitutes a major deviation from the SAR in the simple 2-phenylthiazolidine series. With regard to effects of the length of the aminoalkoxy chain, the ethoxy derivatives were generally more potent than higher analogues. Lengthening of the
N-alkyl group in the (thio) carboxamido group generally caused a decrease in activity. Among the various derivatives synthesized, II
15 was found to be approximately one hundred times more potent than amrinone with a long duration of action.
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HIROYUKI NATE, YASUO SEKINE, KUNIYUKI ODA, KEIICHI AOE, HIDEO NAKAI, H ...
1987 Volume 35 Issue 6 Pages
2412-2418
Published: June 25, 1987
Released on J-STAGE: February 12, 2010
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Optically active isomers of
N-methyl-2- (2- (2- (4-phenylpiperazino) ethoxy) phenyl) thiazolidine-3-carboxamides ((+) -2 and (-) -2) have been synthesized and tested for positive inotropic activity. The racemic thiocarboxamide ((±) -3) was resolved into the enantiomers ((+) -3 and (-) -3) via the L-and D-
N- (2-naphthylsulfonyl) prolyl derivatives ((+) -4 and (-) -4). Conversion of the thiocarboxamides ((+) -3 and (-) -3) to the carboxamides ((+) -2 and (-) -2) was smoothly effected by treatment with the glycidic ester (7). The absolute stereochemistry of (-) -3 was determined to be 2
S by X-ray crystallographic analysis. Hence, the absolute configuration of the carboxamide ((-) -2) is 2
S. On i.v. administration to anesthetized dogs, the enantiomers of 2 showed only a threefold difference in positive inotropic activity, with the
levo isomer ((-) -2) being the more active. In the isolated cat heart muscle, the enantiomers were nearly equipotent to each other. Thus, no significant difference between the positive inotropic activities of the optical isomers of 2 was observed.
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BERNARD VIOSSAT, NGUYEN-HUY DUNG, JEAN-CHARLES LANCELOT, FRANCIS ROBER ...
1987 Volume 35 Issue 6 Pages
2419-2425
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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C
8H
5O
3N
2S
2·C
3H
7NO crystallizes in dimethylformamide as space group
P2
1/
n with lattice parameters
a=10.370 (3),
b=8.180 (8),
c=17.90 (1) Å, β=104.30 (4) °, V=1471 Å
3,
Z=4,
Dm=1.56 (2),
Dx=1.70Mg·m
-3. X-Ray data were collected on an ENRAF-NONIUS CAD-4 diffractometer using Mo
Kα radiation. The crystal structure was solved by direct methods and refined by full matrix least-squares analysis to a final R of 0.049 for 1783 independent reflections. The molecular geometry does not exhibit significant differences between the type I crystal previously described (without the dimethylformamide molecule as solvate) and the type II now studied. The crystal packing is reinforced by N-H…O hydrogen bonding of the amidic group and the DMF molecule. However, in the crystals of type II, the overlapping between adjacent molecules is not observed, contrary to the crystals of type I.
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KAZUO OGAWA, TADAFUMI TERADA, YOSHIYUKI MURANAKA, TOSHIHIRO HAMAKAWA, ...
1987 Volume 35 Issue 6 Pages
2426-2436
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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Various ω-cycloalkyl-2-oxoalkyl arenesulfonates were synthesized and evaluated for esterase-and chymotrypsin-inhibitory activities and hypolipidemic activity. Among the tested compounds, 2-oxoalkyl arenesulfonates (4, 8 and 13) having a cyclohexyl substituent at the terminus of the alkyl chain exhibited considerable esterase-inhibitory activity, and several compounds among 4 and 8 also exhibited potent hypolipidemic action. The structure-activity relationships of these compounds are discussed.
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SUMIO TERADA, TAKU MOTOMIYA, KIMITOMO YOSHIOKA, TOSHIHARU NARITA, SOSU ...
1987 Volume 35 Issue 6 Pages
2437-2442
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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The MeOH extract of
Asarum sagittarioides (Aristolochiaceae) showed antihistaminic activity.
N-Isobutyl-3, 4-methylenedioxybenzamide (1) was isolated as the active principle, and this compound was proved to be an antiallergic substance by pharmacological studies. Furthermore, in order to investigate the structure-activity relationships, some analogues of 1 were synthesized, and compounds 4 and 5 were found to show more potent activity than 1.
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TAICHI OHMOTO, MEGUMI SAITO, KYOKO YAMAGUCHI
1987 Volume 35 Issue 6 Pages
2443-2447
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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Three new compounds have been isolated from the pollen grains of
Cedrus deodara LOUD. and these compounds were determined to be 7β, 18-dihydroxydehydroabietanol (III), 15-methoxyabietic acid (IV) and 9-caffeoyloxyhexadecanol (V) by chemical and spectroscopic methods. 7β-Hydroxydehydroabietic acid (I) and 15-hydroxyabietic acid (II) were also isolated.
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MITSUTERU NUMAZAWA, MASACHIKA TSUJI, CAROL YARBOROUGH, YOSHIO OSAWA
1987 Volume 35 Issue 6 Pages
2448-2452
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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[1, 2-
3H, 4-
14C] 16α-Hydroxyandrostenedione (4) (
3H, 3.20 mCi/mmol;
3H/
14C = 222) was synthesized from commercially available [1, 2-
3H, 4-
14C] dehydroepiandrosterone (1) through bromination at C-16α of the 17-ketone 1 and controlled alkaline hydrolysis of the 16α-bromoketone 3, obtained from the brominated product 2 by 8 N CrO
3 oxidation followed by
p-toluenesulfonic acid treatment, as key reactions. The tritium distribution of the labeled 16α-ketol 4 was determined by chemical and biochemical methods to be 47% at C-1α, 18% at C-2α, and 35% at the β-side of C-1 and C-2. When the labeled ketol 4 was incubated with human placental microsomes and reduced nicotinamide adenine dinucleotide phosphate, the rate of
3H
2O release into the medium was dependent upon protein concentration and incubation time. Aromatase activity obtained by the radiometric assay was comparable to that determined by the high-performance liquid chromatographic method.
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HIROAKI NANBA, KANICHI MORI, TETSURO TOYOMASU, HISATORA KURODA
1987 Volume 35 Issue 6 Pages
2453-2458
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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The powdered fruit bodies of shiitake (
Lentinus edodes) showed antitumor activity when given orally to mice. The growth of tumors, both syngeneic and allogeneic, was inhibited by 57.9 to 78.6% in shiitake-fed mice. The degree of inhibition was proportional to the consumption of the experimental diet (L-feed) and was evident even when the administration was started from the 7th day after tumor implantation. The inhibition of tumor growth was mainly due to a glucan contained in the fruit bodies, but the lipid fracton also had inhibitory effects, although mild. Feeding of the fruit bodies to mice in the diet was found to augment both the ability of macrophages to phagocytose latex particles and the spreading activity of the macrophages.
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HIROAKI NANBA, HISATORA KURODA
1987 Volume 35 Issue 6 Pages
2459-2464
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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When tumor-bearing mice were given diet containing fruit bodies of shiitake (L-feed), the tumor growth was apparently inhibited. To elucidate the mechanisms of this action, the effects of the L-feed on the production superoxide anion (SOA) by macrophages and the cytotoxicity of natural killer T cells were studied. When MM-46 carcinoma-bearing C3H mice were maintained on L-feed (containing 20% shiitake powder), SOA production by macrophages was increased about 2.0 to 2.3 times. Furthermore, the cytotoxic activities of natural killer cells and killer T cells were increased 1.9 times and 1.4 times, compared with their counterparts from normal C3H mice fed on shiitake-free diet. These results suggest that shiitake powder given orally activates various effector cells to attack tumor cells. It appears to potentiate cellular functions and at the same time to prevent a decrease of immune function of the tumor-bearing host.
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HAE YOUNG CHUNG, TAKAKO YOKOZAWA, HIKOKICHI OURA
1987 Volume 35 Issue 6 Pages
2465-2469
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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The renal effect of Salviae miltiorrhizae Radix extract was examined in normal rats. A single intraperitoneal administration of the extract led to appreciable increments of urine volume, and urinary excretion of urea and creatinine. The extract also induced natriuretic, kaliuretic, and phosphaturic responses. Furthermore, treatment with Salviae miltiorrhizae Radix significantly increased glomerular filtration rate, renal plasma flow, and renal blood flow.
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MASAHITO TADA, YOKI MORI
1987 Volume 35 Issue 6 Pages
2470-2477
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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The opsonin-independent recognition of periodate-treated sheep red blood cells (P-SRBC) by macrophages was studied by observation of phagocytosis and the mechanism of the recognition was compared with those for other particles. Thioglycollate-elicited guinea pig peritoneal macrophages time-dependently ingested sheep red blood cells (SRBC) treated with periodate, as well as immunoglobulin G-coated sheep red blood cells (IgG-SRBC), zymosan (Z), serum-treated zymosan (STZ) and latex beads. Trypsinization of macrophages decreased the ingestion of P-SRBC to under 50% of the value of untreated cells and virtually abolished the ingestion of Z and STZ at a concentration that did not inhibit the phagocytosis of IgG-SRBC and latex beads. The decreased activities for P-SRBC recovered to 80% of the control value on incubation of the macrophages for 5 h at 37 °C. The restoration of the ability to ingest P-SRBC following trypsin digestion was inhibited by cycloheximide and tunicamycin. Pretreatment of macrophages with ConA dosedependently decreased ingestion of P-SRBC to under 50% of the original level, but did not decrease the internalization of IgG-SRBC and STZ. Rabbit anti-guinea pig peritoneal macrophage IgG abolished the ingestion of Z and caused marked and slight decreases of.phagocytosis of IgG-SRBC and P-SRBC, respectively.
These results indicated that the site of recognition of P-SRBC on the macrophage cell membrane could be composed of glycoproteins and is distinct from the receptors for C3b and Z. The role of plasma membrane components on macrophages in the action of opsonin-independent recognition is discussed in relation to the opsonin-mediated recognitions.
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YOSHIHISA IWAMOTO, HISASHI YOSHIOKA, YASUTAKE YANAGIHARA
1987 Volume 35 Issue 6 Pages
2478-2483
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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The singlet oxygen-producing activities and photodynamic biological activities of acridine compounds were compared. Singlet oxygen was trapped by 2, 2, 6, 6-tetramethyl-4-piperidone (TEMP), and 2, 2, 6, 6-tetramethyl-4-piperidone-
N-oxyl (TEMPO) produced was detected by electron spin resonance (ESR) spectrometry. TEMPO production was inhibited by NaN
3 and enhanced in D
2O, confirming it to be an adequate ESR spectroscopic indicator for singlet oxygen.
Comparison of TEMPO-producing activities revealed that acriflavine and proflavine, which are the most potent photosensitizers both in cell inactivation and petite induction of yeast, produced the most intense and long-lived ESR signals. However there was no clear difference of TEMPO-producing activity between biologically ineffective acridines such as acridine and quinacrine and effective ones such as acridine yellow and 6, 9-diamino-2-ethoxyacridine.
These results suggested that the differences observed in the photodynamic biological effects among the acridine compounds depend mainly on the differences of drug distribution and only partly on the differences of singlet oxygen-producing activity of the dye molecule itself.
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YASUHIRO KOHAMA, SHIGERU MATSUMOTO, TSUTOMU MIMURA, NOBUKAZU TANABE, A ...
1987 Volume 35 Issue 6 Pages
2484-2489
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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During an initial search for pharmacologically active principles in red-mold rice, two hypotensive compounds were isolated and identified. The active principles, A-3 and B-1, were fractionated and purified from the EtOH extract of red-mold rice prepared with Monascus pilosus through extraction with H
2O, Amberlite CG-120 column chromatographies and high-performance liquid chromatography on an ODS column. A-3 was identified as acetylcholine chloride by comparison with an authentic sample, and B-1, colorless needles of mp 203-205 °C, was proved to be identical with authentic γ-aminobutyric acid. Intravenously administered A-3 (0.5 μg/kg) and B-1 (250μg/kg) produced potent depression of the carotid arterial blood pressure in spontaneously hypotensive rats, as did the corresponding authentic samples.
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SHIZUO NAKAJIN, SHUJI OHNO, MASAYUKI TAKAHASHI, KIYOSHI NISHIMURA, MAS ...
1987 Volume 35 Issue 6 Pages
2490-2494
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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20β-Hydroxysteroid dehydrogenase (20β-HSD) was found in neonatal pig testes. The enzyme catalyzed the reduction of 17α-hydroxyprogesterone to 17α, 2β-dihydroxy-4-pregnen-3-one with oxidation of nicotinamide adenine dinucleotide phosphate, reduced form (NADPH). Identification of 17α, 20β-dihydroxy-4-pregnen-3-one as the product was achieved by thin layer chromatography, gas chromatography, high-performance liquid chromatography, nuclear magnetic resonance spectroscopy and mass spectrometry. 20β-HSD activity was contained in the cytosol fraction of testis but not the microsomal or the mitochondrial fraction. Furthermore, the enzyme required the presence of NADPH or reduced nicotinamide adenine dinucleotide (NADH) as a cofactor, though NADH was far less effective than NADPH. The cytosol fraction of neonatal pig testis contained a large amount of 20β-HSD in comparison with that of mature pig testis. The 20β-HSD activity was also found in the cytosol fraction of mouse, rat, dog and guinea pig testes, but the activities were very low.
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SATOSHI OKADA, HIROSHI NAKAHARA, HIROSHI ISAKA, TOORU TAGA, KOICHIRO M ...
1987 Volume 35 Issue 6 Pages
2495-2503
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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Drugs with a primary aromatic amino moiety such as procaine, procainamide, and
p-aminobenzoic acid (PABA) are capable of reacting with various reducing sugars containing hexoaldoses and pentoaldoses. The amine-carbohydrate reaction products can be separated from the parent drugs by high performance liquid chromatography (HPLC) analysis. The formation and dissociation profiles of the products were followed by HPLC and ultraviolet spectroscopy. The reaction products formed in aqueous solution were not association complexes, but chemical reaction products, which were identified as glycosylamines or
N-glycosides, by comparison with authentic samples obtained by the condensation of amines with carbohydrates in methanol. An X-ray analysis of one of the glycosylamines, 2-deoxy-
N-p-carboxyphenyl-D-ribosylamine, was carried out, and the absolute conformation and configuration in the crystalline state were determined.
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NAONORI KOHRI, KATSUMI MIYAZAKI, TAKAICHI ARITA, HISASHI SHIMONO, AKIK ...
1987 Volume 35 Issue 6 Pages
2504-2509
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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The release characteristics of nifedipine sustained-release granules, composed of ethylcellulose, hydroxypropylmethylcellulose and corn starch, were examined
in vitro as well as in healthy subjects. The release of nifedipine from the granules
in vitro was not first-order, but a linear relationship up to about 40% release was obtained based on the Higuchi equation. The release rate was not strongly influenced by pH, stirring speed, surfactant or ionic strength. These granules were administered to healthy subjects and the plasma levels of nifedipine were compared with those after administration of nifedipine soft gelatin capsule. Plasma levels following the administration of the granules were prolonged as compared with those in the case of the soft gelatin capsule, and plasma levels of about 13 ng/ml at 12 h post-dosing were detected. The known problem of marked inter-subject variability of the plasma levels was not encountered after administration of the sustained-release granules, presumably due to the multiple-units dosage form and the established low sensitivity of the drug release rate to the
in vitro environment,
i.e., pH, stirring speed, surfactant and ionic strength.
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MITSUGU TOMIOKA, Go MATSUMURA
1987 Volume 35 Issue 6 Pages
2510-2518
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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Rheological studies were carried out on aqueous solutions of five methylcellulose (MC) preparations, with degrees of polymerization (DP) between 330 and 1020. Comparison of the intrinsic viscosity of MC with that of sodium carboxymethylcellulose (CMC) of similar DP indicated that MC molecules were relatively compact coils when they were present as isolated coils in dilute solution. However, the Huggins constants (
k'1) of MC samples were higher than those of CMC samples, suggesting that intermolecular interaction of MC was larger than that of CMC at low concentration. The second virial coefficients of MC samples in dilute solution, determined by ultracentrifugation analysis, were divided at about DP 500 int two groups, low and high DP samples. A similar tendency was observed in the rheological properties of concentrated MC solution. It is suggested that the increase in DP was accompanied with an increase not only in molecular size but also in intermolecular interaction of MCs in solution. Interesting rheological characteristics were observed in high DP samples, particularly at concentrations higher than a critical concentration. The dynamic viscoelastic behavior of these samples depended significantly on both DP and concentration.
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YUMIKO NISHIDA, KUNIHIKO MORITA, TAKESHI ONO, HARUMI SHIMAKAWA
1987 Volume 35 Issue 6 Pages
2519-2524
Published: June 25, 1987
Released on J-STAGE: October 19, 2009
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When a solution (pH 4.0) containing 1 mg/ml hen egg-white lysozyme (EC 3.2.1.17) and 1 mM sodium bisulfite (SBS) was stored at 3 °C under scattered light, the residual activity of lysozyme was reduced to about 10% within 3 d. The inactivation was dependent on the pH of the medium, and was especially marked at pH below 5. It was largely prevented by shielding the solution from light, by replacement of the dissolved oxygen in the medium by nitrogen gas and by the addition of several radical scavengers to the medium prior to storage. The absorbance of lysozyme treated with SBS for 3d under scattered light was decreased by about 10% at 280 nm, and the content of tryptophan residues of lysozyme was decreased by about 1.0 mol of Trp/mol of enzyme. The change in the state of aromatic amino acid residues of lysozyme treated with SBS under scattered light was observed by circular dichroism spectral analysis in the wavelength range of 250-340 nm, and this change was prevented by shielding from light and by addition of radical scavengers.
These results suggest that the inactivation of lysozyme during storage in a solution containing SBS was due to modification or destruction of amino acid residues in lysozyme by free radicals formed during the autooxidation of bisulfite under scattered light.
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