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Volume 34, Issue 4
Displaying 1-50 of 63 articles from this issue
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ATSUSHI NISHIDA, MASAKATSU SHIBASAKI, SHIRO IKEGAMI1986 Volume 34 Issue 4 Pages 1423-1433
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSAn efficient preparation of 4-propargyl-2-azetidinone (6) from 4-phenylsulfonyl-2-azetidinone is described. This compound was converted to the ketones 14 and 16, which are the key intermediates for the synthesis of carbapenem and carbacephem antibiotics. In this transformation it was found that polar functional groups (β-lactam, OH, etc.) control the regiochemistry of hydrostannation of the internal alkyne. The reaction of epoxystannanes with formic acid to give the ketones is also described.View full abstractDownload PDF (1169K) -
ATSUSHI NISHIDA, MASAKATSU SHIBASAKI, SHIRO IKEGAMI1986 Volume 34 Issue 4 Pages 1434-1446
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA mild and efficient method for the conversion of propiolic esters to β-keto esters was developed. Initially, propiolic esters were converted to β-phenylthio-α, β-unsaturated esters, which were treated with N-bromoacetamide in an aqueous solvent followed by reductive debromination with an aqueous solution of sodium sulfite, affording β-keto esters in good yields. Using this new method, a formal total synthesis of (±)-thienamycin from 4-propargyl-2-azetidinone was accomplished.View full abstractDownload PDF (1336K) -
YASUO AKITA, AKIRA INOUE, AKIHIRO OHTA1986 Volume 34 Issue 4 Pages 1447-1458
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSVarious chloropyrazines were subjected to cross-coupling reaction with acetylenes, such as phenylacetylene, 1-hexyne and propargyl alcohol, in the presence of palladium catalysts, to give the corresponding coupling products in good yields. It was found that tetrakis(triphenylphosphine)-palladium can catalyze the reaction of chloro-alkylpyrazines, and that a combination of bis-(triphenylphosphine)palladium dichloride and copper(I) iodide preferentially catalyzes the reaction of chloro-phenylpyrazines.View full abstractDownload PDF (853K) -
HIDEYUKI HARUYAMA, HARUMITSU KUWANO, TAKESHI KINOSHITA, AKIRA TERAHARA ...1986 Volume 34 Issue 4 Pages 1459-1467
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSTwo active metabolites of ML-236B, 4β, 6α-dihydroxy ML-236B (M3, 2), and 3β-hydroxy ML-236B (M4, 3), were isolated from the urine of ML-236B-treated dogs. The structures of M3 and M4 were elucidated on the basis of spectral data and confirmed by X-ray analysis.View full abstractDownload PDF (772K) -
MACHIKO ONO, REIKO TODORIKI, SHINZO TAMURA1986 Volume 34 Issue 4 Pages 1468-1472
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSCyclodehydration of β-arylaminocrotonaldehydes (1) was studied kinetically in comparison with those of β-(p-toluidino)acrolein (2a) and 4-(p-toluidino)-3-penten-2-one (3a).The rate constants k1 of cyclodehydration of 1 were not consistent with the Zucker-Hammett hypothesis, i.e., log k1 was related linearly to -H0, but the slopes were between 1.28 and 1.36.Bunnett-Olsen Plots for log k1 were linear. Statistically corrected values of log k0r/KSH+ were applied to Jaffe's four-parameter Hammett equation. The reaction constant for the site of the aromatic ring at which cyclodehydration takes place was evaluated to be -8.54, and that for the oxobutenyl-amino group was evaluated to be +0.72.The effect of substituents on the aromatic ring upon the reactivity is discussed.View full abstractDownload PDF (510K) -
ISAMU MURAKOSHI, FUMIO IKEGAMI, YOSHIHIRO YONEDA, HARUMI IHARA, KUMIKO ...1986 Volume 34 Issue 4 Pages 1473-1478
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSSeveral heterocyclic β-substituted alanines were biomimetically synthesized by incubating 0.1 M acetate buffer solution containing the appropriate heterocyclic compound and O-acetylserine or serine in the presence of pyridoxal 5'-phosphate (PLP) and metal ions. This PLP-catalyzed chemical reaction depends upon pH, metal ions and temperature. The addition of Ga3+, Fe3+ or Al3+ enhanced the rate of synthesis. The optimum of the various reaction conditions of this biomimetic method is described.View full abstractDownload PDF (690K) -
HARUO OGURA, HIDESHI FUJITA, KIMIO FURUHATA, MASAYOSHI ITOH, YOSHIYASU ...1986 Volume 34 Issue 4 Pages 1479-1484
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSSome N-acetyl-D-neuraminec acid nucleoside analogs were synthesized. Methyl penta-O-acetyl-N-acetyl-D-neuraminate (1) was treated with trimethylsilyl-pyrimidine or -5-fluoropyrimidine and tin(IV) chloride to give a mixture of α- and β-anomers of N-nucleoside analogs. On the other hand, methyl tetra-O-acetyl-N-acetyl-2-chloro-β-D-neuraminate was allowed to react with trimethylsilyl-pyrimidine or -5-fluoropyrimidine under the Koenigs-Knorr reaction conditions to provide the β-anomer in a fair yield. The stereochemistry of these compounds was confirmed by measurements of the rate of hydrolysis of the glycosidic bond with water.View full abstractDownload PDF (577K) -
TAKUZO HISANO, KAZUNOBU HARANO, RYUICHI FUKUOKA, TOSHIKAZU MATSUOKA, K ...1986 Volume 34 Issue 4 Pages 1485-1492
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe cycloaddition reactivity of tosyl isocyanate toward pyridine N-oxides was calculated by the CNDO/2 method using a perturbation equation, and the results indicated that the initial stage of the reaction might be controlled by the coulombic attraction. The 1, 3-dipolar cycloaddition reaction of tosyl isocyanate with two equivalents of 3, 5-dibromopyridine N-oxide in refluxing benzene gave 6-bromo-2-oxooxazolo[4, 5-b]pyridine, while the use of one equivalent of 3, 5-dichloropyridine N-oxide gave 6, 7a-dichloro-2-oxo-3-tosyl-3a, 7a-dihydrooxazolo[4-, 5-b]pyridine, formed from the 1, 5-sigmatropic rearrangement of the corresponding primary cycloadduct. When the reaction was carried out in the presence of triethylamine in benzene, 6-halogeno-2-oxo-3-tosyloxazolo[4, 5-b]pyridine was isolated.The observed activation parameters, as well as the small solvent effects, may be interpreted in termas of a concerted pathway.The reaction should be very valuable as a one-pot synthesis of 2-oxooxazolo[4, 5-b]pyridines, which are pyridine analogues of 5-chloro-2-benzoxazolinone.View full abstractDownload PDF (792K) -
CHUN-SHENG CHIEN, ATSUSHI HASEGAWA, TOMOMI KAWASAKI, MASANORI SAKAMOTO1986 Volume 34 Issue 4 Pages 1493-1496
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA novel and efficient synthesis of 1-acylindoxyls (3) from 1-acylindoles (1) is described. The procedure involves the demethoxylation with stannic chroride of 1-acyl-3-hydroxy-2-methoxy-indoline (2), which were obtained by the MoO5 oxidation of 1in methoanol. Since the MoO5 oxidation of 2-substituted 1-acylindoles (1f and 1g) gave not the corresponding indolines (2f and 2g), but 2-hydroxyindoxyls (4f and 4g), 2f and 2g were obtained by the methylation of 4f and 4g with diazomethane to give 5f and 5g, followed by the reduction of 5f and 5g with sodium borohydride, respectively.View full abstractDownload PDF (565K) -
YASUO FUJIMOTO, EIZO YOKOYAMA, TATSUYUKI TAKAHASHI, JUN UZAWA, NOBUHIS ...1986 Volume 34 Issue 4 Pages 1497-1500
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThree new trihydroxytetralones (1, 2 and 3) have been isolated from the culture broth of P.diversum var. aureum together with three known naphthalenones (sclerone, isosclerone and juglone). The structure of 1 was determined on the basis of its chemical properties and spectroscopic analyses of the monomethyl ether (4) and dimethyl ether (5).View full abstractDownload PDF (496K) -
KIYOSHI TOMIOKA, TSUNEO ISHIGURO, YOICHI IITAKA, KENJI KOGA1986 Volume 34 Issue 4 Pages 1501-1504
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSNew steganacin analogs with definite absolute configurations, (-)-picro- and (-)-epipicrosteganol, were synthesized by isomerization of (-)-steganol and (-)-episteganol, respectively, at the α-position to the lactone carbonyl. The structure of (-)-epipicrosteganol was confirmed by X-ray crystallographic analysis. Selective epimerization at the C-4 benzylic position was observed upon acidic treatment of (-)-steganacin, giving (-)-episteganacin.View full abstractDownload PDF (499K) -
TOSHIHIKO NAITO, YOSHIHIKO MAKITA, SHIOMI YAZAKI, CHIKARA KANEKO1986 Volume 34 Issue 4 Pages 1505-1517
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS2-Chloro-1, 4-naphthoquinone undergoes photochemical 2+2 addition to alkenes. Elimination of hydrogen chloride from the adducts provides a facile and general synthetic method for 1, 2-dihydrocyclobuta[b]naphthalene-3, 8-diones. Heating of the latter compounds affords 2, 3-dimethylene-1, 2, 3, 4-tetrahydronaphthalene-1, 4-diones, which react in situ with alkenes to give the 4+2 adducts. 1-Formyl-1, 2-dihydrocyclobuta[b]naphthalene-3, 8-dione obtained by the use of the above two-step procedure using acrolein dimethylacetal as the alkene in the first step affords upon heating 1H-naphtho[2, 3-c]pyran-2, 10-dione via electrocyclization of the corresponding dimethylenecompound. If an enone is used as the alkene in the first step, the addition occurs in a 4+2 manner to give directly 4H-naphtho[2, 3-b]pyra-5, 10-diones.View full abstractDownload PDF (1264K) -
HIROYUKI USUI, TOHRU UEDA1986 Volume 34 Issue 4 Pages 1518-1523
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSTreatment of 3', 5'-O-(tetraisopropyldisiloxane-1, 3-diyl)-2'-ketoadenosine (1) with methylenetriphenylphosphorane gave the 2'-methylene derivative (2). Hydroxylation of 1 with OsO4 gave the 2'-hydroxymethyladenosine (4), which was then converted to the 2'-phenylthiomethyl derivative (5). Photocyclization followed by deprotection of the product furnished 8, 2'-methanoadenosine (7), and adenosine fixed in a high-anti conformation. Oxidation of a 2'-hydroxyethylideneadenosine with OsO4 gave the 2'-dihydroxyethyladenosine (10), which was also converted to the 2'-(2-phenylthioethyl) derivative (11). The photocyclization of 11 and successive elimination of the hydroxyl group gave the 8, 2'-ethenoadenosine (13). Catalytic hydrogenation and deprotection of 13 afforded 8, 2'-ethanoadenosine (15). The circular dichroism spectral features of C-cycloadenosine are discussed.View full abstractDownload PDF (746K) -
SHIGEHIRO MORI, TOYOHIKO AOYAMA, TAKAYUKI SHIOIRI1986 Volume 34 Issue 4 Pages 1524-1530
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSAromatic and heteroaromatic organometallics (Grignard and Iithium compounds) react with diphenyl phosphorazidate (DPPA) to give labile phosphinyltriazenes. A study of the conversion of phosphinyltriazenes into amines has revealed that reductive work-up with aluminum hydride gives much better results than acidic or alkaline work-up. Sequential treatment of aromatic and heteroaromatic organometallics with DPPA, followed by aluminum hydride provides a convenient new method for the preparation of aromatic and heteroaromatic amines.View full abstractDownload PDF (662K) -
MICHIYO SUZUKI, YOSHIKAZU KIMURA, SHIRO TERASHIMA1986 Volume 34 Issue 4 Pages 1531-1539
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe title cerium(III) reagents (7-10) were found to react with 5, 8-dimethoxy-2-tetralone (11a) and 5, 12-dihydroxy-1, 2, 3, 4-tetrahydronaphthacene-2, 6, 11-trione (15) more efficiently than the corresponding lithium and magnesium reagents (3, 5, and 4, 6), giving the addition products (12a, 13a, and 17) in high yields. Hydration of these adducts readily afforded the α-hydroxy methyl ketones, 2-acetyl-5, 8-dimethoxy-1, 2, 3, 4-tetrahydro-2-naphthol (14a), and 2-acetyl-2, 5, 12-trihydroxy-1, 2, 3, 4-tetrahydronaphthacene-6, 11-dione (4-demethoxy-7-deoxydaunomycinone) (18), which are versatile synthetic intermediates for optically active 4-demethoxyanthracyclinones.View full abstractDownload PDF (975K) -
KIMIYE BABA, KAZUO TAKEUCHI, MITSUNOBU DOI, MASATOSHI INOUE, MITSUGI K ...1986 Volume 34 Issue 4 Pages 1540-1545
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe absolute configurations of daphnodorin A (1) and daphnodorin B (2) isolated from Daphne odora THUNB. (Thymelaeaceae) were studied, and 1 was assigned as C-2 (S), while 2 was assigned as C-2 (R), C-3 (S) on the basis of chemical transformations and spectral analyses. An X-ray analysis of daphnodorin A pentamethyl ether (4) was performed and two conformers (A and B) due to restricted rotation of the trioxy-benzoyl group were observed.View full abstractDownload PDF (550K) -
TAKABUMI NAGAI, ITSUMARO KUMADAKI, TAKUICHI MIKI, YOSHIRO KOBAYASHI, G ...1986 Volume 34 Issue 4 Pages 1546-1552
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe ene reaction of 1, 1, 1-trifluoroacetone with various olefinic compounds proceeded in the presence of aluminum chloride at low temperature to give allylmethyl (trifluoromethyl)carbinols. Olefinic compounds with a terminal vinyl group reacted smoothyl, but some olefins with an inner double bond did not react at all. Trifluoroacetone was also found to undergo a Friedel-Crafts type reaction with aromatic compounds.View full abstractDownload PDF (766K) -
KAZUO SATO, TAKAO KINOTO, SOJI SUGAI1986 Volume 34 Issue 4 Pages 1553-1560
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe reaction of (N-aryl-N-hydroxy)acylacetamides 11 with p-nitrobenzenesulfonyl chloride in the presence of 2 eq of triethylamine gave 5-alkyl-3-aryl-4-oxazolin-2-ones 10. In the same manner, 5-alkyl-3-aryl-4-halogeno-4-oxazolin-2-ones 14 were synthesized from the corresponding N-aryl-N-hydroxy-α-halogeno-acylacetamides 12, which were prepared by chlorination or bromination of (N-aryl-N-hydroxy)acylacetamides 11.View full abstractDownload PDF (621K) -
HIDETOSHI TAKAGI, TOMOKO SONEDA, TOSHIAKI MIURA, MICHIYA KIMURA1986 Volume 34 Issue 4 Pages 1561-1567
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe mechanism of the color reaction of deoxycorticosterone (1) with sulfuric acid was elucidated. Two rearranged products, 13ξ(or 14ξ)-hydroxy-17β-methyl-18-nor-13ξ, 14ξ, 17α-pregn-4-ene-3, 20-dione (4) and 17β-methyl-18-nor-17α-pregna-4, 13-diene-3, 20-dione (5), were isolated from the reaction mixture of 1 with 97% sulfuric acid at room temperature in 46 and 32% yields, respectively. Proton nuclear magnetic resonance (1H-HMR) spectra of 97% sulfuric acid solutions of 1, 4 and 5 revealed that they are present in the acid as the diprotonated form (7) of 5, showing an absorption maximum at 288 nm. The acid solution of 7 was heated for 90 min at 60°C to give two intermediary species (x-372 and x-436) showing maxiama at 372 and 436 nm, respectively. Dilution of the mixture with ethanol reduced these species and produced a new chromophore (x-600) showing a maximum at 600 nm. From the diluted solution, 17-isopropyl-18-norandrosta-4, 6, 8(14), 13(17)-tetraen-3-one (13) was isolated in 13% yield. Dissolution of 13 in a 2 : 3 mixture of sulfuric acid and ethanol immediately gave x-600, which was identified from its 1H-NMR data as the steroidal carbocation (14) having a hydroxyalkatetraenyl cation moiety. On the other hand, dissolution of 13 in 90% sulfuric acid gave x-372, which was shown to be in acid-base equilibrium with x-600. x-372 was also identified from its 1H-NMR data as the dication (15) having a hydroxyalkenyl cation moiety in ring A and an Alkadienyl cation moiety across rings B, C and D.View full abstractDownload PDF (696K) -
YOSHIRO KOBAYASHI, MASAKAZU NAKAZAWA, ITSUMARO KUMADAKI, TAKEO TAGUCHI ...1986 Volume 34 Issue 4 Pages 1568-1572
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSReaction of 3, 6β-diacetoxycholest-2-ene (2) with cesium fluoroxysulfate gave 6β-acetoxy-2α-fluorocholestan-3-one (3), which was successfully converted to 2α-fluorovitamin D3 (10). A single dose of 500 ng of 10 produced an intestinal calcium transport response and a bone calcium mobilization response in vitamin D-deficient rats equivalent to those of vitamin D3.View full abstractDownload PDF (591K) -
AKIRA MATSUDA, TOHRU UEDA1986 Volume 34 Issue 4 Pages 1573-1578
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSFor studies of the conformation of nucleosides around the glycosyl linkages, the carbonbridged cycloadenosines, 8, 6'-cyclo-6'-deoxyallofuranosyladenine and its 5'-epimer, were synthesized by the following route. Treatment of N6-benzoyl-2', 3'-O-isopropylideneadenosine 5'-aldehyde (1) with dimethyloxosulfonium methylide afforded the 5', 6'-anhydrohexofuranosyladenine (2), which was treated with thiophenoxide to give the diastereomeric 6'-phenylthio derivatives (4). Photoirradiation of 4 followed by 5'-O-acetylation afforded 5'-O-acetyl-8, 6'-cyclo-6'-deoxy-hexofuranosyladenine derivatives (6b, 7b). Attempted synthesis of a 8, 7'-cyclo-heptofuranosyl derivative by way of photolysis of a 7'-phenylthio-heptofuranosyladenine resulted in the formation of 5', 6', 7'-trideoxy-2', 3'-O-isopropylidene-β-D-ribo-heptofuranosyladenine (11). The nature of the circular dichroism spectra of 6 and 7 is discussed.View full abstractDownload PDF (739K) -
KIYOSHI IKEDA, KAZUO ACHIWA, MINORU SEKIYA1986 Volume 34 Issue 4 Pages 1579-1583
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSIntroduction of the secondary aminomethyl grouping RNHCH2 into carboxylates at the α-position has been achieved by reaction of hexahydro-1, 3, 5-triazines with ketene silyl acetals in the presence of a catalytic amount of trifluoromethanesulfonic acid.View full abstractDownload PDF (498K) -
TOSHIO SUZUKI, ETSUKO SATO, KATSUO UNNO, TETSUJI KAMETANI1986 Volume 34 Issue 4 Pages 1584-1588
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe total synthesis of (-)-dihydrocorynantheol (3) has achieved using a potentially useful chiral synthon, thioketal carboxylic acid (8), derived from (R)-1, 2-isopropylideneglyceraldehyde (4) in 7 steps.View full abstractDownload PDF (547K) -
SACHIO OHNO, OSAMU KOMATSU, KIYOSHI MIZUKOSHI, KENJI ICHIHARA, YOSHIKI ...1986 Volume 34 Issue 4 Pages 1589-1606
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSAsymmetric 4-aryl-1, 4-dihydro-2, 6-dimethyl-3, 5-pyridinedicarboxylates with a 2-ethylenedioxypropyl, 2-oxopropyl, or cyclopropylmethyl group as the ester moiety and related derivatives were synthesized and tested for vasodilating activity in anesthetized open-chest dogs and for antihypertensive activity in conscious spontaneously hypertensive rats. Cyclopropylmethyl methyl 1, 4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3, 5-pyridinedicarboxylate (5f, MPC-2101) and methyl 2-oxopropyl 1, 4-dihydro-2, 6-dimethyl-4-(2-nitrophenyl)-3, 5-pyridinedicarboxylate (8i, MPC-1304) exhibited potent cerebral vasodilating and antihypertensive activities, respectively. The maximum increase of vertebral blood flow after intravenous administration at 3.0 μg/kg was 221.4% for 5f, compared with 187.0 and 166.3% for nifedipine and nicardipine hydrochloride, respectively. The maximum falls of systolic blood pressure after oral administration of 8i at 0.3 and 1.0 mg/kg were 42.2 and 54.0 mmHg, while those of nifedipine, nicardipine, and hydralazine hydrochloride at 3.0 mg/kg were 23.3, 16.8, and 24.5 mmHg, respectively. The durations of significant vasodilating and antihypertensive effects for 5f and 8i were longer than those of nifedipine and nicardipine.View full abstractDownload PDF (1460K) -
SABURO SUGAI, TOKUJI OKAZAKI, YOSHIO KAJIWARA, TOSHIFUMI KANBARA, YASU ...1986 Volume 34 Issue 4 Pages 1607-1612
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS17-Methoxyacetate (3a) and 17-(methylthio)acetate (3b) of 11β, 17α, 21-trihydroxy-6α-methyl-1, 4-pregnadiene-3, 20-dione (6α-methylprednisolone, 1) and their 21-esters (4a and 4b) were synthesized and tested for vasoconstrictive activities. The activities of the 17-(methylthio)acetate derivatives (3b and 4b) were more potent than those of the corresponding 17-methoxyacetates (3a and 4a). The activities of 3b, 4a2, 4b1-4 and 4b5 were equivalent to that of 9α-fluoro-11β, 21-dihydroxy-16β-methyl-17α-valeroyloxy-1, 4-pregnadiene-3, 20-dione (betamethasone 17-valerate, BV). The reaction of 6α-methylprednisolone (1) with triethyl orthomethoxyacetate afforded a stereoisomeric mixture of 6α-methylprednisolone 17, 21-cyclic ortho esters (2aA and 2aB) in a ratio of 22 : 78, while the reaction of 1 with triethyl ortho(methylthio)acetate resulted in the formation of a single isomer (2bB) of the isomeric 17, 21-cyclic ortho esters (2b).View full abstractDownload PDF (730K) -
SABURO SUGAI, YOSHIO KAJIWARA, TOSHIFUMI KANBARA, YASUO NAITO, SEIICHI ...1986 Volume 34 Issue 4 Pages 1613-1618
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS17α-Acyloxy-11β, 21-dihydroxy-2'-phenyl-2'H-2, 4-pregandieno[3, 2-c]pyrazol-20-one derivatives (3a, 3b, 4, 5a and 5c) were synthesized and tested for vasoconstrictive activities. Compound 3b showed the most potent activity, which was greater than that of 9α-fluoro-11β, 21-dihydroxy-16β-methyl-17α-valeroyloxy-1, 4-pregnadiene-3, 20-dione (betamethasone 17-valerate, BV). The activities of all other compounds (3a, 4, 5b and 5c) were rather weaker than that of the mother compound, 11β, 17α, 21-trihydroxy-2'-phenyl-2'H-2, .4-pregnadieno[3, 2-c]pyrazol-20-one (1). In contrast to the case of corticosteroids having a hydrocortisone-type skeleton, esterification of both the 17- and 21-hydroxy groups of the pyrazole-fused compound (1) or the substitution of the 21-hydroxy group of the 17-ester compound (3) with a chlorine atom are not always necessary for the exhibition of higher activity.View full abstractDownload PDF (630K) -
DANIEL DAUZONNE, RENE ROYER1986 Volume 34 Issue 4 Pages 1628-1633
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA convenient one-step procedure to synthesize the title compounds (3a-v) by the reaction between 1, 2, 3-trimethoxy-5-(2-nitroethyl)benzene (1) and aromatic or heterocyclic aldehydes is reported. The obtained 1-aryl-2-nitro-3-(3, 4, 5-trimethoxyphenyl)propenes can easily be reduced to provide new mescaline derivatives. As an example, 1-(3-indolyl)-2-amino-3-(3, 4, 5-trimethoxyphenyl)propane (4), which contains in the same molecule the structural features of both mescaline and tryptamine, has been prepared.View full abstractDownload PDF (638K) -
TOCHIRO TATEE, SHUJI KURASHIGE, AKIRA SHIOZAWA, KAZUHISA NARITA, MASAO ...1986 Volume 34 Issue 4 Pages 1634-1642
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA series of 5-amino-3-phenylisoxazole derivatives was synthesized and evaluated as part of a search for new types of centrally acting muscle relaxants. The derivtives with an alkylaminopropyl moiety exhibited muscle relaxant activity comparable to that of tolperisone (1), but this activity was accompanied by strong general central nervous system (CNS) depressant and slight anticonvulsant activities.On the other hand, the derivative with a propanamide moiety exhibited a favorable pharmacological profile for a selective muscle relaxant with little CNS depressant action.View full abstractDownload PDF (900K) -
TOCHIRO TATEE, KAZUHISA NARITA, SHUJI KURASHIGE, SHINJI ITO, HIROSHI M ...1986 Volume 34 Issue 4 Pages 1643-1655
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSN-Substituted 3-amino-2-methyl-N-(3-phenyl-5-isoxazolyl)propanamide derivatives (5a-w) were prepared, and their muscle relaxant and anticonvulsant activities were evaluatd. Among the compounds with high potency, 3-diethylamino-2, N-dimethyl-N-(3-phenyl-5-isoxazolyl)propanamide (5e) was found to possess selective muscle relaxant and anticonvulsant activities. Compounds with carbon side chains other than the 2-methylpropanamide moiety did not give increased muscle relaxant activity. Optical isomers of 5e were prepared from metyl (+)-and (-)-3-diethylamino-2-methylpropionates (15a, b), and the (+)-isomer (5x)b was found to be twice as potent as the (-)-isomer (5y). The structure-activity relationship was studied with emphasis on the effects of the 3-amino moiety and of the substituent on the isoxazolyl 5-amino group. A good quadratic correlation equation was found between hydrophobicity and muscle relaxant activity.View full abstractDownload PDF (1009K) -
MUNEKAZU IINUMA, YOSHINOBU MATOBA, TOSHIYUKI TANAKA, MIZUO MIZUNO1986 Volume 34 Issue 4 Pages 1656-1662
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSFour flavones oxygenated at C-2', 3', 4' and 6', and seven flavonols oxygenated at C-2', 4' and 5', each with a 5, 6, 7-trioxygenated structure in ring A, were synthesized for comparison with brickellin and apulein. The structures of brickelin and apulein were thus confirmed to be 2', 5-dihydroxy-3, 4', 5', 6, 7-pentamethoxyflavone and 2', 5'-dihydroxy-3, 4', 5, 6, 7-pentamethoxyflavone, respectively. The differences between flavones oxygenated at 2', 3', 4' and 6', and flavonols oxygenated at C-2', 4', 5' are discussed on the basis of spectroscopic data.View full abstractDownload PDF (811K) -
HISAYUKI KANAMORI, IKUNORI SAKAMOTO, MARI MIZUTA, OSAMU TANAKA1986 Volume 34 Issue 4 Pages 1663-1666
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe methanolic extract of Swertiae Herba after treatment with nitrite was mutagenic to Salmonella typhimurium TA 98 in the absence of S9 mix. Two active principles were isolated and identified as amarogentin and amaroswerin, and this activity was proved to be associated with their 3, 3', 5-trihydroxybiphenylcarboxylic acid moiety. 3, 3'5-Trihydroxybiphenyl obtained from both the glucosides also exhibited mutagenicity after treatment with nitrite. Such activity was not observed for the non-acylated swecoiridoid glucosides and xanthone homologues of this drug.Quantitative analysis of the above two active glucosides in the commercial plant was also conducted.View full abstractDownload PDF (527K) -
TOSHIYUKI TANAKA, MUNEKAZU IINUMA, MIZUO MIZUNO1986 Volume 34 Issue 4 Pages 1667-1671
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe ultraviolet, proton nuclear magnetic resonance and mass spectra of 56 flavones were measured, and the data were applied for the structure elucidation of 2'-oxygenated flavones.View full abstractDownload PDF (545K) -
GISHO HONDA, YASUHIKO KOEZUKA, WASUKE KAMISAKO, MAMORU TABATA1986 Volume 34 Issue 4 Pages 1672-1677
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe MeOH extract of Perilla frutescens leaves, which are used as a sedative in Chinese traditional medicine, was fractionated to isolate its active constituents. The progress of the fractionation was followed by measuring the prolongation of hexobarbital-induced sleep in mice. The activity was mainly due to the presence of both perillaldehyde and stigmasterol.View full abstractDownload PDF (600K) -
KENICHIRO NAKASHIMA, KEN'ICHI NISHIDA, SHIN'ICHI NAKATSUJI, SHUZO AKIY ...1986 Volume 34 Issue 4 Pages 1678-1683
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA method for the determination of thiol compounds is described. A new fluorogenic reagent, N-{p-[2-(6-dimethylamino)benzofuranyl]phenyl}maleimide, has been found to give fluorescent products when reacted with certain biological thiols, e.g., reduced glutathione and cysteine. The reaction is very sensitive, and concentrations as low as 10-9 M can be detected. Disulfides such as oxidized glutathione and cystine can also be determined after reduction of the disulfide to thiol with KBH4. The proposed method has been successfully applied to the determination of total thiol compounds in rat tissues and rat blood.View full abstractDownload PDF (554K) -
KENICHIRO NAKASHIMA, KEN'ICHI NISHIDA, SHIN'ICHI NAKATSUJI, SHUZO AKIY ...1986 Volume 34 Issue 4 Pages 1684-1687
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA fluorometric method for the determination of rat liver glutathione peroxidase (GSH-Px) activity has been developed, based on the determination of the concentration of unreacted reduced glutathione in the assay mixture with N-{p-[2-(6-dimethylamino)benzofuranyl]phenyl}maleimide as a fluorogenic reagent. This method is very sensitive and can assay GSH-Px activity in 50 μg wet weight of rat liver. A linear relationship was obtained between GSH-Px activity and amount of sample over the range of 10-100 μg protein. GSH-Px activities obtained by this method correlated well with those obtained by the conventional colorimetric method with 5, 5'-dithiobis(2-nitrobenzoic acid).View full abstractDownload PDF (462K) -
KATSUYA WADA, TSUTOMU MASUJIMA, HISANOBU YOSHIDA, TERUO MURAKAMI, NOBO ...1986 Volume 34 Issue 4 Pages 1688-1693
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSPhotoacoustic microscopy was applied ot the determination of dye (alcian blue 8GS) spotted on a mucin layer. The determination range in a 40 μm diameter area was 40-1200 pg. The total dye quantity in the spot (ca. 2mm diameter) was determined by integrating the quantities in the 40 μm diameter area within 15% error, irrespective of the uniformity of the distribution. This method was applied to the analysis of acidic mucopoly-saccharide in the rat rectum and in rat eyeball sections stained with alcian blue 8GS. The dye quantity was estimated to be 40-640 pg in the microregion of 40 μm diameter area and 1.5-1.8 μg in the whole region in ca. 8 μm thick sections. These quantities corresponded to 1.6-26 ng and 60-72 μg of mucin, respectively, based on the weight binding ratio of 40 of mucin to the dye in solution.View full abstractDownload PDF (649K) -
KYOJI YOSHINO, TOSHIKI MATSUURA, MITSUAKI SANO, SHIN-ICHI SAITO, ISAO ...1986 Volume 34 Issue 4 Pages 1694-1700
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA fluorometric method for the determination of aliphatic aldehydes using 1, 3-cyclohexanedione reagent and high-performance liquid chromatography (HPLC) was developed.Straight-chain aldehydes of C3-C10 were reacted with 1, 3-cyclohexanedione at 60°C for 1 h and the fluorescent decahydroacridine derivatives2, 3) formed were determined by HPLC on an ODS column. The calibration curves for the aldehydes were linear in the range of 0-10 ng and the relative standard deviation at the 5 ng level was about 2.3%.This method was sensitive enough to measure the amount of aliphatic aldehydes, including 4-hydroxynonenal, generated by microsomal peroxidation in rat liver.View full abstractDownload PDF (618K) -
KATSUYOSHI NAKAJIMA, HAJIME KOTAKI, YUKIYA SAITOH, FUJIO NAKAGAWA1986 Volume 34 Issue 4 Pages 1701-1708
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA method is described for the determination of methylphenidate and its main metabolite, ritalinic acid, in plasma from various species, based on gas chromatography-chemical ionization mass spectrometry using ethylphenidate as an internal standard. Methylphenidate in plasma is extracted with cyclohexane and converted to the pentafluoropropionyl (PFP) derivative. Ritalinic acid is extracted with 2-propanol from the salt-saturated remaining aqueous phase, converted to the parent drug by treatment with a mixture of methanol and sulfuric acid (2 : 1, v/v), and then converted to the PFP derivative. The protonated molecular ions at m/z 380 for the PFP derivative of methylphenidate and m/z 394 for that of the internal standard were used for selected ion monitoring analysis. The hydrolysis of methylphenidate in plasma before the addition of the internal standard could be prevented completely by holding the plasma sample at around 0°C. The limit of quantitation was 0.5 ng for methylphenidate and 2.5 ng for ritalinic acid using 0.5 ml of plasma. The present method is highly sensitive and reliable, and should be satisfactory for application to pharmacokinetic studies of methylphenidate in laboratory animals and man.View full abstractDownload PDF (839K) -
NAOHITO OHNO, YOSHIYUKI ADACHI, IWAO SUZUKI, KICHIRO SATO, SHOZO OIKAW ...1986 Volume 34 Issue 4 Pages 1709-1715
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSChemical characterization of the extracts, and purification and structural characterization of an antitumor glucan obtained from liquid-cultured mycelium of Grifola frondosa are described in this paper. The mycelium (13 g dry weight/1 culture) was extracted successively with hot water (LMHW, 14.9 g/100 g mycelium), cold alkali (LMCA, 6.3 g/100 g mycelium), and hot alkali (LMHA, 4.5 g/100 g mycelium). Each extract was dialyzed and then the polysaccharide fraction was precipitated with ethanol. Another portion of the mycelium was incubated with a buffer composed of glucose (5.0%) and citric acid, pH 4.5, for 3 d and the supernatant was obtained (LELFD, 50 g/100 g mycelium). The brothe was dialyzed and the nondialyzable fraction was precipitated with ethanol (LLFD, 1.3 g/1 culture). All of the above fractions were composed of glucose as the major carbohydrate. Except for LMHW, all fractions showed antitumor activity against sarcoma 180 cells in ICR mice. The activity was the strongest in the LELFD fraction. Antitumor glucan (grifolan LE) was purified from LELFD by diethylaminoethyl-Sephadex A-25 chromatography and ethanol precipitation. Grifolan LE gave Mr of more than 5×106 (8 M urea/0.2 N NaOH), [α]D -6°--9° (c=0.1%; 0.3 N NaOH), and showed metachromasy coupled with Congo red. By carbon-13 nuclear magnetic resonance spectra and methylationanalyses, grifolan LE was found to be a branched β-1, 3-glucan containing a branch at C-6 of every three main chain glucosyl units.View full abstractDownload PDF (651K) -
HIROSHI TSUJIBO, TORU TANIGUCHI, ISAO KOYAMA, MAYURI KUBO, YOSHIHIKO I ...1986 Volume 34 Issue 4 Pages 1716-1720
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSFrom the dried body of Naja naja Kaouthia from which the internal organs had been removed, three hypotensive compounds were isolated and one of them was identified as inosine.Inosine produced a transient increase in blood pressure followed by a prolonged fall lasting for 30 min in spontaneously hypertensive rats. Next, the relationship between the chemical structure and the hypotensive effect was examined by studying ribose-modified derivatives of inosine. 2'-Deoxyinosine and 3'-deoxyinosine completely lacked hypotensive effect. Phosphorylation at the 3' or 5'-position except for inosine 5'-diphosphoribose and 5'-chloro-5'-deoxyinosine slightly decreased the hypotensive effect. The results indicate that the ribose configuration is important in relation to the hypotensive effect of inosine.View full abstractDownload PDF (545K) -
KUNIHISA AKAI, MASAAKI GOTO, MASATSUGU UEDA1986 Volume 34 Issue 4 Pages 1721-1727
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThree kinds of monoclonal antibodies directed to human epidermal growth factor (hEGF) were obtained. One of them did not react with mouse epidermal growth factor (mEGF) but the others showed reactivity with mEGF. Antibody having binding ability to both hEGF and mEGF was suitable for the purification of EGFs. Human EGF was isolated from normal adult human urine in a high yield by means of a simple purification process using an immunoadsorbent column of monoclonal antibody. Mouse EGF was also purified from mouse submaxillary gland using the same immunoadsorbent column and a Sephadex G-50 column. Both of the purified EGFs gave a single band with an apparent molecular weight of 6000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The amino acid sequences were consistent with those reported previously.View full abstractDownload PDF (832K) -
ATSUSHI HAKURA, YUTAKA KAWAZOE1986 Volume 34 Issue 4 Pages 1728-1734
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSAn attempt was made to establish a procedure for kinetic formulation of the mutagenic chemical modification of the mutational target(s), even though the mutational initiaiton processes are unclear. Using the proposed kinetic formulation, a quantitative analysis was made of the temperature dependence of mutation frequency in terms of the activation energies for mutagenic modification induced in the cell by mutagens. E. coli B Hs30R (uvrA) was treated with alkyl methanesulfonates and N-alkyl-N-nitrosoureas at 37, 25 and 15°C for 1 h and the induced mutation frequencies were normalized in terms of the concentration-time integrated dose. The plot of the normalized mutation frequency versus the reciprocal of the reaction temperature gave a straight line which corresponds to the Arrhenius plot, enabling us to estimate the apparent activation energy of the initial chemical event leading to mutation. It is worth emphasizing that the activation energy evaluated from a certain biological end-point, the mutagenicity in the present study, may cast light on the chemical characteristics of the induced chemical event leading to the end-point concerned.View full abstractDownload PDF (710K) -
YOSHIHISA IWAMOTO, YASUTAKE YANAGIHARA, LERENA W. YIELDING, K. LEMONE ...1986 Volume 34 Issue 4 Pages 1735-1739
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSPromotive effects of propidum iodide (PI) on petite induction by 8-deaminoethidium chloride (8-DAEC) were examined. 8-DAEC was a potent petite inducer in growing yeast cells but not in resting yeast cells. Addition of PI promoted the petite induction by 8-DAEC throughout the cultivation time at a concentration that was ineffective by itself. In resting cells, petites were scarcely induced by either 8-DAEC or PI or both, even after prolonged incubation. Notable sectored colony induction was observed after prolonged incubation of the yeast cells with either 8-DAEC or PI in phosphate·buffer. The petite induction by ethidium bromide (EB) was not accelerated but was delayed in PI-pretreated cells, whereas the simultaneous presence of PI promoted the EB mutagenesis.These results suggested that the simultaneous presence of PI and petite inducer in growth medium was required in order to exhibit the promotive effects. Possible mechanisms of the differences in the process of petite induction between resting and growing cells are discussed.View full abstractDownload PDF (588K) -
YUJI SUGITA, TOWORU OMATA, TAKASHI TOBE, TERUFUMI SAKAMOTO, MOTOWO TOM ...1986 Volume 34 Issue 4 Pages 1740-1747
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe recovery of catalase in the microsomal fraction of rat liver was influenced by the solution used for preparation. When microsomes were prepared with TMKS-solution (50 mM Tris-HCl, pH 7.4, 5 mM MgCl2, 25 mM KCl and 0.25 M sucrose), the catalase content of the microsomes (TMKS-microsomes) was about 50% of that in the microsomes (PS-microsomes )prepared with PS-solution (10 mM phosphate buffer, pH 7.0, and 0.25 M sucrose).Upon washing of PS-microsomes with 0.25 M sucrose containing 50 mM Tris, about 30% of catalase as well as fatty acyl-CoA oxidase, both being peroxisomal enzymes, was released. On the other hand, membrane marker enzymes, glucose-6-phosphatase and nucleoside diphosphatase, and a secretory albumin, were not substantially released by this treatment. No effect was observed on the release of catalase by washing PS-microsomes with 0.25 M sucrose containing MgCl2 or KCl, but Tris caused selective release of catalase.These two types of microsomal catalase, i.e., that released by Tris (TS-released catalase) and that not released (TS-microsomal catalase), were labeled by injection of 3H-leucine. A peak in the specific radioactivity appeared in the former at 50 min and in the latter at 30 min after the injection, and both thereafter lost their labels rapidly. Based on these results, a possible intracellular transition of catalase, TS-microsomal catalase &;DDotrahd TS-released catalase &;DDotrahd peroxisomal catalase, is discussed.View full abstractDownload PDF (899K) -
TETSUYA SOMENO, SHIN-ICHI ISHII1986 Volume 34 Issue 4 Pages 1748-1754
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA simple method was developed for the conversion of leupeptin (acetyl-Leu-Leu-argininal) to other peptidyl argininals. Argininal dibutylacetal, a key intermediate, was produced by enzymatic digestion of leupeptin dibutylacetal with Pronase E and was isolated by column chromatography on CM-52 cellulose. Nα-Blocked peptides (or amino acids) were connected to the α-amino group of this intermediate by conventional methods, and finally the acetal protecting group was removed by mild acid treatment to recover the essential aldehyde function. This novel method is applicable to large-scale preparation of many kinds of peptidyl argininals, which are promising candidates as specific inhibitors of trypsin-family proteases.View full abstractDownload PDF (716K) -
YUTAKA KAWAZOE, TOSHIHARU FUJIURA, KOHFUKU KOHDA1986 Volume 34 Issue 4 Pages 1755-1763
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA simple and reliable method is proposed to determine if a mutagen requires any metabolic activation for its genotoxicity. It consists of a comparison of the mutation frequencies induced in tester bacteria treated with the mutagen in the presence and absence of butyl isothiocyanate (Bu-NCS), a non-specific enzyme inhibitor. A mutagen requiring metabolic activation mutates the cells to a lesser extent in the presence of Bu-NCS, whereas direct-acting mutagens are capable of mutating the cells to the same extent in the presence or absence of this inhibitor. Bu-NCS seems to more or less inhibit the metabolizing ability of the enzymers present in the tester cells without any subsequent effects on the cells' viability or mutability after the inhibitor is removed. The tester bacteria to be used should preferably be deficient in the excision repair mechanism for induced deoxyribonucleic acid damage. When a carcinogen is mutagenic in such a tester bacterial system, this method would predict the ultimate, i.e., direct-acting, structure of the carcinogen because a common ultimate reactive species should be responsible for both mutagenicity and carcinogenicity. The validity of this method was tested by using 17 models of mutagenic carcinogens and the resuls supported the reliability of the prediction. Some limitations to the applicability of this method are discussed.View full abstractDownload PDF (799K) -
MATSUJI HARA, HIDEHUMI HAYASHI, TSUGUCHIKA YOSHIDA, HIROSHI MURAYAMA1986 Volume 34 Issue 4 Pages 1764-1769
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe kinetics and mechanism of the degradation of chlorphenesin carbamate (α-CPC) in strongly alkaline aqueous solutions were studied at 0 to 20°C. The degradation did not obey pseudo-first order kinetics, but was shoun to involve a complex reaction accompanied by consecutive, parallel and reverse reactions. The rate law of degradation could be approximated in terms of specific base-catalyzed hydrolysis, that is k=kOH αOH, from the rate constant-pH profile. The Arrhenius plots of the degradation were approximately linear. Chlorphenesin-2-carbamate (β-CPC) and chlorphenesin (CP) were detected as alkaline degradation products of α-CPC.The mechanism proposed for the degradation of α-CPC involves migration of the carbamoyl group to the adjacent OH group and removal of the carbamoyl group in the presence of hydroxide ions.View full abstractDownload PDF (557K) -
TERUTAKA TAKAHASHI, IZUMI KAGAMI, KENZO KITAMURA, YUTAKA NAKANISHI, YU ...1986 Volume 34 Issue 4 Pages 1770-1774
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSStabilization of AD-1590 in an oleaginous suppository by complexation with β-cyclodextrin (β-CvD) was investigated. Suppositories were stored at 37°C and 75% relative humidity. AD-1590 was rapidly decomposed by autoxidation in the case of the suppository containing only AD-1590. On the other hand, no decomposition was observed in the case of the suppository containing AD-1590-β-CyD complex. The stabilizing effect of complexation is considered to be attributable to insolubilization of AD-1590 in the oleaginous base. The release rate was also promoted by complexation. These results indicate that complexation with CyDs is a promising means of improving the bioavailability and the stability of drugs which are very unstable when solubilized in an oleaginous base.View full abstractDownload PDF (585K) -
YOSHINOBU TAKAKURA, KUNI MORI, MITSURU HASHIDA, HITOSHI SEZAKI1986 Volume 34 Issue 4 Pages 1775-1783
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe absorption characteristics of several kinds of macromolecular compounds following intramuscular injection were studied in rats. Three types of 14C-labeled mitomycin C-dextran conjugates (14C-MMC-D), bare 14C-dextran, 14C-inulin, and 131I-albumin were used, and their absorption and subsequent lymphatic uptake were determined by radioactivity counting. Clearance of cationic 14C-MMC-D from the injection site was slow and varied with the molecular weight. Remarkable accumulation of radioactivity was observed in the regional lymph node after injection of 14C-MMC-D. Bare 14C-dextran showed similar behavior, but the rate of clearance was faster and less accumulation in the lymph node was observed compared with 14C-MMC-D of the same molecular weight. In contrast, 14C-inulin and 131I-albumin showed rapid disappearance from the muscle and no accumulation in the lymph node. Muscular absorption data were fitted to a compartment model including a Langmuir-type absorption. Pharmacokinetic analysis revealed that the rate of absorption and the degree of absorption depended on the molecular weight and electric charge, and MMC-D with a molecular weight of 500000 proved to have the longest period of residence. Thus, it was elucidated that physicochemical properites, such as molecular weight and electric charge, affect the pharmacokinetic behavior of macromolecular compounds injected topically.View full abstractDownload PDF (925K) -
MAKOTO OTSUKA, TAKAHIRO MATSUMOTO, NOBUYOSHI KANENIWA1986 Volume 34 Issue 4 Pages 1784-1793
Published: April 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe effect of grinding in an agate centrifugal ball mill at 200 rpm on the physicochemical properties of indomethacin (IMC) polymorphs was studied by means of X-ray diffraction analysis, infrared spectroscopy and differential scanning calorimetry. The α and γ forms (metastable and stable forms) of IMC were ground at 4°C ant at 30±0.5°C, and the degree of crystallinity (Xc) of the ground products was measured by the X-ray diffractional internal standard method.The Xc of the γ form ground at 4°C decreased with increasing grinding time, and was 0% after 4 h, that is, the γ form had been converted to a noncrystalline solid. After grinding for 1 h at 30°C, about 45% of γ form of IMC was converted to noncrystalline solid, while the product ground for 10 h was transformed to the α form.The Xc of the α form ground for 2 h at 4°C was 0%, that is, the αform had been converted to a noncrystalline solid within 2 h at 4°C. The Xc of the α form ground at 30°C decreased with increasing grinding time and the value after 10 h was about 60%.The solubility in distilled water at 35°C of the γ form ground for 10 h at 4°C was about 60% larger than that of the intact γ form. The solubilities of the γ form gournd for 10 h at 30°C, the α form gound for 10 h at 4°C and the α form gound for 10 h at 30°C were all the same, 0.94 mg/100 ml, which is equal to that of the α form at 35°C.View full abstractDownload PDF (933K)