Chemical and Pharmaceutical Bulletin

Studies on Coenzyme Analogs. XIX. Further Investigations of Phosphorylation Using Morpholinophosphorodichloridate and P¹-Diphenyl P²-Morpholino Pyrophosphorochloridate.

Morio Ikehara, Eiko Ohtsuka

1963 Volume 11 Issue 11 Pages 1353-1358
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1353

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The phosphorylation of unprotected nucleoside, 9-D-erythrityladenine and adenosine, was attempted by the use of P¹-diphenyl P²-morpholino pyrophosphorochloridate. Whereas in the former case 23% of 4'-monophosphate was obtained, the yield of 5'-AMP was very low. Isopropylideneadenosine was phosphorylated with Vilsmeier complex derived from morpholinophosphorodichloridate in 50% yield. The use of DMF in the reaction of isopropylidene-AMP-morpholidate was also investigated. 2', 3'-O-Isopropylidene-ATP was synthesized and characterized.

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Studies of Nucleosides and Nucleotides. XXI. A New Synthesis of Thymidine 5'-Triphosphate and the Use of P¹, P²-Di-(2-cyanoethyl) pyrophosphate in the Nucleoside Triphosphate Synthesis.

Morio Ikehara, Eiko Ohtsuka

1963 Volume 11 Issue 11 Pages 1358-1363
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1358

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A new synthesis of thymidine 5'-triphosphate was achieved by the phosphorylation with P¹-diphenyl P²-morpholino pyrophosphorochloridate of 3'-O-acetylthymidine, followed by the reaction with pyrophosphate salt and alkaline removal of acetyl group. The reaction of 2', 3'-O-isopropylideneadenosine 5'-phosphoromorpholinochloridate with P¹, P²-di-(2-cyanoethyl) pyrophosphate was also investigated. After the alkaline removal of protecting groups only isopropylidene-ADP was obtained.

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Color Reaction Mechanism of Anthrone with Sugars. (2). Some Reaction Products of Furfural with Anthrone (Organic Analysis. XLVII)

Tsutomu Momose, Yosuke Ohkura, Kazumasa Hirauchi

1963 Volume 11 Issue 11 Pages 1364-1368
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1364

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A crystalline dye was separated from the reaction mixture of anthrone with furfural or xylose in sulfuric acid, and its probable structure was presented. The same dye was also yielded by condensing anthrone to another dye which was separated from the reaction mixture of the same reagents in phosphoric acid.

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Studies on the Pyrimidine Derivatives. XXIV. Syntheses of Several Thiol-type Thiamine Derivatives and their Primary Screening Tests.

Akira Takamizawa, Kentaro Hirai, Yoshio Hamashima, Hisao Sato

1963 Volume 11 Issue 11 Pages 1368-1375
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1368

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The new thiamine derivatives, O-substituted derivatives of thiamine propyl disulfide, disulfide derivatives of thiamine and 2-hydroxy-3-carbamoyloxypropyl, 2-ethoxycarbonylethyl, 2-ethoxycarbonyloxyethyl, and their O-substituted derivatives were prepared. Also, O-2-tetrahydropyranyl derivatives of S-alkoxycarbonyl thiamine and thiamine propyl disulfide were prepared, and their primary screening tests were made.

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Benzimidazole N-Oxides. I. The Structure of Benzimidazole N-Oxide and Synthesis of its Derivatives.

Shiro Takahashi, Hideo Kano

1963 Volume 11 Issue 11 Pages 1375-1381
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1375

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Previously unknown 1-substituted benzimidazole 3-oxides were synthesized by reductive ring-closure of N-acyl-N-substituted-o-nitroanilines. From the ultraviolet absorption spectra, it was shown that benzimidazole N-oxide exists as the N-oxide form in aqueous solution and as the N-hydroxyl form in ethanol solution.

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Syntheses of Pyrimidinylhydrazones of 4-Biphenylylglyoxal

Kaname Takagi, Takeo Ueda

1963 Volume 11 Issue 11 Pages 1382-1388
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1382

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To search for antimicrobial agent, 2-hydrazino-4-alkoxy-6-methylpyrimidine, 2-hydrazino-4-alkylthio-6-methylpyrimidine, and 2-alkylthio-4-hydrazino-6-methylpyrimidine were synthesized by the hydrazination of the corresponding 2-chloro- and 4-chloropyrimidine with hydrazine hydrate, and it was found that chlorine atom at 2-position or 4-position in pyrimidine ring, is more reactive on hydrazine than alkylthio and alkoxy group at 4- or 2-position. These hydrazinopyrimidines of the three series were converted into pyrimidinylhydrazones of 4-biphenylylglyoxal by the condensation with 4-biphenylylglyoxal.

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Studies on Tablet Disintegration. I. The Effect of Penetrating Rate on Tablet Disintegration.

Hisashi Nogami, Hisashi Fukuzawa, Yoshinobu Nakai

1963 Volume 11 Issue 11 Pages 1389-1398
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1389

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The effects of the penetrating rate on tablet disintegration were examined. Viscosity, surface tension, contact angle of liquid and the mean capillary diameter of tablet were measured and their effects on disintegration were discussed. In high viscosity solution, the rate of penetration decreased and the disintegration was not well. The viscosity of gastric juice was measured and tablet disintegration in human gastro-intestinal tract was examined by X ray. It was estimated that a tablet disintegration might be affected by the viscosity of gastric juice. The rate of penetration of powder in a surfactant solutions and the penetration of the powder coated by surfactant in pure water were measured. The effect of surfactant on disintegration could not be generally expected due to the decrease of surface tension. The mean diameter of open capillary in a tablet was measured by air permeametry. The diameter was decreased by a large compressional force in tableting and increased by a large quantity of disintegrator. The equation of penetrating rate was discussed theoretically to apply it for the penetrating in tablet capillary. It was concluded that Washburn's equation of penetrating rate could be applied to the penetrating in the capillary of a tablet.

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Modifications of Nucleosides and Nucleotides. I. Reaction of Ethylene Oxide with Uridine and Uridylic Acid.

Tyunosin Ukita, Harumi Okuyama, Hikoya Hayatsu

1963 Volume 11 Issue 11 Pages 1399-1404
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1399

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The reaction of ethylene oxide with uridine derivatives in an aqueous solution at room temperature was investigated. 1-Methyluracil gave 1-methyl-3-(2-hydroxyethyl)-uracil (II) quantitatively upon reaction with ethylene oxide at pH 10. The reaction of uridine with ethylene oxide at neutral pH results in the formation of 3-(2-hydroxyethyl)-uridine (IV) quantitatively. These products, II and IV, were isolated as crystals and the structure well defined. The rate of N³-alkylation of uridine increases with the increase of pH value. This indicated that the reaction proceeds through the dissociated form of uridine. At a high-pH region, alkylation of the hydroxyl group(s) of ribose moiety took place concomitantly with the N³-alkylation and gave multiply 2-hydroxyethylated derivatives of uridine. In the reaction of uridine 5'-phosphate with ethylene oxide, besides the N³-hydroxyethylation, phosphodiester formation was also observed. In a high-pH solution, the hydroxyethylation of sugar-hydroxyl group(s) took place as in the case of uridine. Synthesis of uridine 5'-phosphate 2-hydroxyethyl ester by the reaction of uridine 5'-phosphate with ethylene glycol in the presence of dicyclohexyl carbodiimide was described.

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Organometallic Compounds. II. Gas Chromatography of Metal Acetylacetonates.

Koji Yamakawa, Keiichi Tanikawa, Kiichi Arakawa

1963 Volume 11 Issue 11 Pages 1405-1408
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1405

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Gas chromatography of twenty kinds of metal acetylacetonates [Al (III), Ba (II), Be (II), Ca (II), Cd (II), Co (II), Co (III), Cr (III), Cu (II), Fe (III), Mg (II), Mn (II), Mn (III), MoO₂ (VI), Ni (II), Th (IV), Ti (III), VO (IV), Zn (II), and Zr (IV)] was investigated, using various liquid-phase column. Analysis of the metal chelates was effected by the use of a column of 0.5% silicon polymers (SE-30, SE-52, and QF-1) on glass microbeads.

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Studies on Steroidal Compounds. IX. Preparation of 17α-Chloro Steroids.

Hiromu Mori, Shunyo Wada

1963 Volume 11 Issue 11 Pages 1409-1413
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1409

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Some hydroxy-steroids were transformed into the corresponding chloro-steroids with Walden inversion, when treated with sulfuryl chloride in pyridine ; testosterone (I), 4-chlorotestosterone (IV), 17β-hydroxy-5α-androstan-3-one (V), 5α-androstane-3β, 17β-diol 3-acetate (VIII), and estradiol 3-benzoate (IX) were introduced to the corresponding 17α-chloro compounds, II, III, VI, VIIa, and X, respectively. From androsterone (XI) and isoandrosterone (XIV) were obtained 3β-chloro-5α-androstan-17-one (XII) and 3α-chloro-5α-androstan-17-one (XIII) respectively.

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Studies on Steroidal Compounds. X. Preparation of 17β-Chloro Steroids.

Hiromu Mori, Kiyoshi Tsuneda

1963 Volume 11 Issue 11 Pages 1413-1417
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1413

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17β-Chloro-5α-androstan-3β-ol (VII) and 17β-chloro-5α-androstan-3-one (VI) were prepared. 3β-Hydroxy-5α-androstan-17-one hydrazone (II) was treated with N-chlorosuccinimide in pyridine to give 17-chloro-5α-androst-16-en-3β-ol (IVa), which on hydrogenation with 5% palladium charcoal afforded VII. The chromium trioxide oxidation of VII gave VI. Some observations concerning 17-bromo and 17-iodo compounds (IVb and III) were also written.

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Studies on Steroidal Compounds. XI. Reaction of 5-Ene Steroids with Sulfuryl Chloride in Pyridine.

Hiromu Mori, Joji Yamada

1963 Volume 11 Issue 11 Pages 1418-1423
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1418

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Some 3β-acetoxy-5-ene steroids were reacted with sulfuryl chloride in pyridine and the corresponding 3β-acetoxy-5α, 6β-dichloro steroids were obtained. Dehydroepiandrosterone acetate (VII) was transformed into 5α, 6β, 16, 16-tetrachloro compound (VI) on treatment with sulfuryl chloride in chloroform. The reaction of androst-5-ene-3, 17-dione (IX) with sulfuryl chloride in pyridine gave 6α-chloroandrost-4-ene-3, 17-dione (X), whereas the same reaction on pregn-5-ene-3, 20-dione (V) afforded the corresponding 5α, 6β-dichloro compound (IIIa). Some transformations of compounds above-mentioned were also written.

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Studies on Seven-membered Ring Compounds. VIII. Syntheses of 5-Nitrosotropolone Derivatives.

Genshun Sunagawa, Yasunobu Sato, Mitsuo Watatani

1963 Volume 11 Issue 11 Pages 1423-1431
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1423

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3-Substituted 5-nitrosotropolone (IIIa∼c), 7H-cyclohepta [b] pyrazin-7-one oxime (VIIIa, b), 8H-cyclohepta [b] quinoxalin-8-one oxime (IXa∼c), 9H-cyclohepta [b] naphtho [2, 3-e] pyrazin-9-one oxime (X), 5-nitrosotropolone guanidine adduct (XI), 2-(2-acetylhydrazino)-5-nitrosotropone (XII and its analogues) and 2-(2-troponylhydrazino)-5-nitrosotropone (XIV) were synthesized according to the schemes shown in Chart 1, 2, and 3. In addition, some reactions related to IIIa and IIIc were described. Among these derivatives, 2-(2-isonicotinoylhydrazino)-5-nitrosotropone and its N-oxide showed remarkable anti-tumor activities on ascitic and solid forms of Ehrlich tumor and Sarcoma 180.

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Studies on Seven-membered Ring Compounds. X. Nitration of 5-Hydroxycyclohepta [b] pyrrol-6 (1H)-one Derivatives and their Rearrangement Reaction to Indole Derivatives.

Yasunobu Sato

1963 Volume 11 Issue 11 Pages 1431-1440
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1431

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3-Aryl-5-hydroxycyclohepta [b] pyrrol-6 (1H)-one were synthesized by the similar manner as previously described. Nitration of 5-hydroxycyclohepta [b] pyrrol-6 (1H)-one derivatives (VII and Va) gave mononitro derivatives (VIIIa and VIIIb). The properties of the mononitro derivatives (VIIIa and VIIIb) were examined and it was discovered that VIIIa and VIIIb underwent rearrangement by aqueous alkali to 4-nitroindole derivatives (Xa and Xb). In order to determine the structure of the products being obtained by the rearrangement reaction, the cyclization of phenylpyruvic acid 4-carboxy-3-nitrophenylhydrazone (XIVa) was investigated. Moreover, the nitro groups of the products were proved to be in 4-potition by infrared spectra analysis and oxidative degradations. Therefore, above-mentioned mononitro derivatives were established to be 4-nitro-5-hydroxycylohepta [b] pyrrol-6 (1H)-one derivatives.

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Studies on Seven-membered Ring Compounds. XI. Bromination of 5-Hydroxycyclohepta [b] pyrrol-6 (1H)-one Derivatives and Synthesis of 3-(2-Aminoethyl)-2-carboxy-5-hydroxycyclohepta [b] pyrrol-6 (1H)-one.

Yasunobu Sato

1963 Volume 11 Issue 11 Pages 1440-1445
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1440

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Bromination of 5-hydroxycyclohepta [b] pyrrol-6 (1H) -one was examined. Namely, bromination of 2-ethoxycarbonyl-5-hydroxy-3-phenylcyclohepta [b] pyrrol-6 (1H)-one (Ib) afforded only 4-bromo-2-ethoxycarbonyl-5-hydroxy-3-phenylcyclohepta [b] pyrrol-6 (1H)-one (IIb), and 5-hydroxy-3-phenylcyclohepta [b] pyrrol-6 (1H) -one (VI) afforded 2-bromo (VII), and 2, 4-dibromo-5-hydroxy-3-phenylcyclohepta [b] pyrrol-6 (1H)-one (VIII). Hydrolysis of IIb with alkali afforded 4-bromo-2-carboxy-5-hydroxy-3-phenylcyclohepta [b] pyrrol-6 (1H)-one (III) without rearrangement reaction. Reaction of III with aqueous ammonia afforded 2-carboxy-4, 5-dihydroxy-3-phenylcyclohepta [b] pyrrol-6 (1H)-one (V). A sevenmembered ring compound having a similar structure to serotonin, 3- (2-aminoethyl) -2-carboxy-5-hydroxycyclohepta [b] pyrrol-6 (1H)-one hydrochloride (XII) was prepared.

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Synthesis of the Heterocyclic Compounds by Pschorr Cyclization. II. Syntheses of Substituted-6, 7-dihydrobenzo [a] quinolizinium Salts.

Sanya Akaboshi, Toshio Kato, Akisuke Saiga

1963 Volume 11 Issue 11 Pages 1446-1451
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1446

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The Pschorr reaction of 1- (2-amino-4, 5-methylenedioxyphenethyl) pyridinium (Va'), 1- (2-amino-4, 5-dimethoxyphenethyl) pyridinium (Vb) and 1- (2-amino-4, 5-dimethoxyphenethyl) picolinium (Vc) salts was carried out and the corresponding cyclized product was obtained respectively. 2-Amino-1- (3, 4-methylenedioxyphenethyl) pyridinium salt was prepared and its Pschorr reaction was investigated.

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Studies on the Constituents of Asclepiadaceae Plants. XII. On the Components of Pergularia extensa N. E. Br. (Daemia extensa R. Br.).

Hiroshi Mitsuhashi, Marekichi Sasaki, Yuzuru Shimizu

1963 Volume 11 Issue 11 Pages 1452-1455
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1452

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The whole plant of Perugularia extensa N. E. Br. was proved to contain a glycoside mixture which showed strong Keller-Kiliani reaction, suggesting the presence of a 2-deoxy-sugars in the sugar part. The sugar fraction obtained by acid hydrolysis was found to contain D-cymarose, D-sarmentose, L-oleandrose, and D-glucose by a paper chromatographic comparison with authentic specimens. Uzarigenin and a new glycoside (m.p. 244∼248°) were found.

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Studies on Coenzyme Analogs. XVII. A New Phosphorylating Agent, 2, 6-Lupetidylphos-phorodichloridate, and Some Investigations on the Selective Phosphorylation.

Morio Ikehara, Eiko Ohtsuka, Yoshihiro Kodama

1963 Volume 11 Issue 11 Pages 1456-1461
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1456

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By the reaction of 2, 6-lupetidine with phosphorus oxychloride a new phosphorylating agent, 2, 6-lupetidylphorodichloridate was synthesized. Unprotected adenosine was phosphorylated with this reagent on 5'-hydroxyl group in a yield around 15%.

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Studies on the Metabolism of Borate. III. Variations of Fructose 6-Phosphate Levels and Fructose 1, 6-Diphosphate Levels in some Organs and Blood after Administration of Borate, and Effects of Boron on Anaerobic Glycolysis.

Masuo Akagi, Takayuki Misawa, Hiroyasu Kaneshima

1963 Volume 11 Issue 11 Pages 1461-1464
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1461

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Both the levels of fructose-6-phosphate (F6P) and fructose 1, 6-diphosphate (FDP) in biological materials such as livers, brains, kidneys and blood of rats and guinea pigs were investigated at 4 hours after oral administration of borax in a single dose of 140 mg. and 240 mg./kg. as boron to the former animals and to the latter respectively, and boron effects upon anaerobic glycolysis were also examined with liver homogenates and brain homogenates of rats. FDP levels in livers of these animals received borax had a tendency to rise obviously within 4 hours. Anaerobic glycolysis of glucose was found to be inhibited considerably by boron (0.01 M boric acid), being the inhibition rates higher with liver homogenates than with brain homogenates of rats.

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Structure of Leucotylin

Itiro Yosioka, Tsutomu Nakanishi

1963 Volume 11 Issue 11 Pages 1468-1470
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1468

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A New Synthetic Method of Nucleosides

Takuzo Nishimura, Bunji Shimizu, Issei Iwai

1963 Volume 11 Issue 11 Pages 1470-1472
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1470

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Pyridazinenitriles

Hiroshi Igeta

1963 Volume 11 Issue 11 Pages 1472-1473
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1472

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Die Konstitution und Konfiguration der Tetrodonsaure

Kyosuke Tsuda, Chihiro Tamura, Ryuji Tachikawa, Kiyoshi Sakai, Osamu A ...

1963 Volume 11 Issue 11 Pages 1473-1475
Published: November 25, 1963
Released on J-STAGE: March 31, 2008

DOIhttps://doi.org/10.1248/cpb.11.1473

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