著者

藤井 澄三 小川 和男 板谷 泰助 伊達 忠正 稲垣 甚一郎 野原 富士夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.3, pp.408-413, 1995-03-15 (Released:2008-03-31)

参考文献数

25

被引用文献数

2 3

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A full account is given of the first syntheses of 6-mercaptopurine 7-N-oxide (4) and 6-methylthiopurine 7-N-oxide (5). The synthesis of 4 followed a "phenacylamine route", which started from condensation of 4, 6-dichloro-5-nitropyrimidine (15) with N-(4-methoxybenzyl)phenacylamine to form the phenacylaminopyrimidine derivative (11) and proceeded through conversion into the mercapto derivative, intramolecular cyclization between the NO2 nitrogen atom and the phenacyl carbanion to give 6-mercapto-9-(4-methoxybenzyl)purine 7-N-oxide (12), and removal of the 4-methoxybenzyl group. S-Methylation of 12 and removal of the 4-methoxybenzyl group afforded 5. The location of the oxygen function in 4, 5, and 12 was confirmed by X-ray crystallographic analysis of 5·H2O, which was shown to exist in the N(7)-OH form (19). A UV spectroscopic approach suggested that the neutral species of 4 exists in HO as the N(7)-OH tautomer (21), whereas that of 5 exists as an equilibrated mixture of the N(7)-oxide (5) and the N(7)-OH (19) tautomers. In the in vitro bioassay of antileukemic activity against murine L5178Y cells, the N-oxides 4 and 12 were found to be weakly cytotoxic.

著者

板谷 泰助 小川 和男 松本 浩郎 渡辺 朝子

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.28, no.9, pp.2819-2824, 1980-09-25 (Released:2008-03-31)

参考文献数

11

被引用文献数

7 8

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Heating N, N-diethyl-3, 9-dialkyladeninium halides (Ig-j) in aqueous sodium hydroxide gave 1-alkyl-5-(alkylamino)imidazole-4-carboxamides (IV) together with minor amounts of 1-alkyl-5-(alkylamino)imidazole-4-carbonitriles (III), which were converted into IV on further heating. N, N-Dimethyl-3, 9-dialkyladeninium halides (Ia-d) underwent hydrolysis more rapidly to provide IV selectively in 90-94% yields.

著者

藤井 澄三 小川 和男 斎藤 徹 板谷 泰助 伊藤 忠正 岡村 公生

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.2, pp.321-324, 1995-02-15 (Released:2008-03-31)

参考文献数

26

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Oxidation of 1-benzyladenine (12) with m-chloroperoxybenzoic acid in MeOH or in MeOH-0.5 M phosphate buffer (pH 6.6) has been found to afford 1-benzyladenine 7-oxide (13) as the main product. Nonreductive debenzylation of 13 gave adenine 7-oxide (14) in 63% yield. The structure of 13 was unequivocally established by an X-ray crystallographic analysis.

著者

藤井 澄三 小川 和男 斎藤 徹 小林 恵子 板谷 泰助 伊達 忠正 岡村 公生

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.1, pp.53-62, 1995-01-15 (Released:2008-03-31)

参考文献数

49

被引用文献数

3 4

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A detailed account is given of the first unequivocal synthesis of adenine 7-oxide (8). The synthesis started with peroxycarboxylic acid oxidation of 3-benzyladenine (6), readily obtainable from adenine (1) by benzylation, and proceeded through nonreductive debenzylation of the resulting 3-benzyladenine 7-oxide (7). The location of the oxygen function in 7 and 8 was confirmed by their chemical reactions including deamination and methylation and by X-ray crystallographic analysis. A UV spectroscopic approach suggested that the neutral species of 8 exists in H2O as an equilibrated mixture of the N(7)-oxide (8) and N(7)-OH (21) tautomers. Treatment of 6 with 30% aqueous H2O2 in MeOH in the presence of MeCN and KHCO3 at 30°C produced the N(7)-oxide 7 and 7-acetamido-3-benzyladenine (15) in 12% and 1% yields, respectively.

著者

小川 和男 西井 正廣 稲垣 甚一郎 野原 富士夫 斎藤 徹 板谷 泰助 藤井 澄三

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.40, no.5, pp.1315-1317, 1992-05-25 (Released:2008-03-31)

参考文献数

16

被引用文献数

2 7

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The synthesis of 8-methylguanine 7-oxide (3) was accomplished via a "phenacylamine route", which started from condensation of α-(4-methoxybenzylamino)propiophenone (6), prepared by coupling of α-bromopropiophenone (4) and 4-methoxybenzylamine (5), with 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone (7) and proceeded through cyclization of the resulting phenacylaminopyrimidinone (8) and removal of the 4-methoxybenzyl group. The N-oxide 3 and its 9-arylmethyl derivatives 9 and 11 showed only very weak antileukemic activity and no antimicrobial activity.

著者

小川 和男 西井 正廣 稲垣 甚一郎 野原 富士夫 斎藤 徹 板谷 泰助 藤井 澄三

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.40, no.2, pp.343-350, 1992-02-25 (Released:2008-03-31)

参考文献数

47

被引用文献数

8 10

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A full account is given of the first chemical synthesis of the antitumor antibiotic guanine 7-oxide (5) and its 9-substituted derivatives (24a-k and 26). Coupling of appropriate primary amines (17a-e, g-k) with phanecyl bromide (16) produced, after treatment with HCl, the corresponding N-substituted phenacylamine hydrochlorides (18a-e, g-k). A similar phenacylation of 4-amino-1-butanol (21) failed to give the desired compound 18f, so that 21 was heated with 2-bromomethyl-2-phenyl-1, 3-dioxolane (20) at 150-155°C for 3h to furnish, after treatment with HCl, the amino ketal hydrochloride 22 in 40% yield. Deketalization of 22 with hot 2N aqueous HCl afforded 18f in 96% yield. Condensations of the free bases, generated in situ from the hydrochlorides 18a-l and 1N aqueous NaOH, with the chloropyrimidinone 6 were effected in aqueous EtOH at the boiling point for 20 min or at 25-30°C for 3-24h, giving the 6-phenacylamino-4-pyrimidinones 19a-l in 54-90% yields. On treatment with 2N aqueous NaOH at room temperature for 10-60 min, the nitropyrimidinones 19a-k cyclized to provide the 9-substituted guanine 7-oxides 24a-k in 61-98% yields. A similar alkali-treatment of 19l failed to yield guanine 7-oxide (5). However, removal of the 9-(arylmethyl) group from 24i-k was effected with conc, H2SO4 at room temperature for 1-3h in the presence of toluene, producing the target N-oxide 5 in 56-89% yields. In the in vitro bioassay of antileukemic activity against murine L5178Y cells, none of the 9-substituted guanine 7-oxides (24a-k and 26) was more effective than the parent, natural N-oxide 5. Within this series, however, the benzyl analogues 24g-k with or without alkoxy functions were more cytotoxic, with IC50's of 13.0-48.0μg/ml, than the alkyl analogues 24a-f.

著者

板谷 泰助 小川 和男

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.33, no.5, pp.1906-1913, 1985-05-25 (Released:2008-03-31)

参考文献数

32

被引用文献数

2 4

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Reaction of 1-methyl-5-(methylamino) imidazole-4-carboxamide (6a) with a boiling mixture of ethyl orthoformate and acetic anhydride produced 3, 9-dimethylhypoxanthine (7a) in 60% yield and 1-methyl-5-(N-methylformamido) imidazole-4-carboxamide (5a) in 39% yield. Compound 5a was transformed into 7a by treatment with NaH in 78% yield. Compound 7a was alternatively prepared by cyclocondensation of 6a with diethoxymethane followed by oxidation with I2. The pyrimidine moiety of 7a has been shown to be reactive : 7a affords the 1, 2-dihydro derivative 9 under reductive conditions and undergoes ring opening to 5a in aqueous NaOH. 3-Ethyl-9-methyl-(7b), 3-benzyl-9-methyl-(7c), 9-ethyl-3-methyl-(7d), and 3, 9-dibenzylhypoxanthine (7e) were also prepared from the corresponding carboxamides 6b-e.

著者

板谷 泰助 松本 浩郎 渡辺 朝子 原田 恒博

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.33, no.6, pp.2339-2347, 1985-06-25 (Released:2008-03-31)

参考文献数

34

被引用文献数

10 17

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Treatment of 5-(methylamino)-1-β-D-ribofuranosylimidazole-4-carboxamide (5a) with CNBr in acetate buffer gave the 5-cyanomethylamino derivative 6a, which was cyclized to 3-methyl-guanosine (7) in the presence of NaOEt. Cyclocondensation of 7 with bromoacetone in the presence of K2CO3 provided 3-β-D-ribofuranosylwye (2), the most probable structure for the fluorescent nucleoside from Torulopsis utilis phenylalanine transfer ribonucleic acid (tRNAPhe). The glycosidic bonds of 2 and 7 have been shown to be unusually subject to cleavage under either acidic or basic conditions, but proved to be less labile under neutral conditions, as had been reported. The base moiety of 2 is also cleaved under basic conditions.

著者

藤井 澄三 高田 泰孝 小川 和男 板谷 泰助 松原 聰

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.2, pp.325-327, 1995-02-15 (Released:2008-03-31)

参考文献数

20

被引用文献数

2

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Treatment of N6-benzyladenine (2) with 15% aqueous H2O2 in trifluoroacetic acid at 65-70°C for 1 h was found to give the N(3)-oxide (3) and the N(7)-oxide (4) in 4% and 4% yields, respectively. The structure of 3 was established by its identity with a sample prepared from 6-chloropurine 3-oxide (6) and benzylamine, and the structure of 4 by its identity with a sample obtained from 1-benzyladenine 7-oxide (8) by Dimroth rearrangement. The N-oxides 3 and 4, together with previously reported N6-benzyladenine 1-oxide (1), were tested for cytokinin activity in the tobacco callus bioassay. Each of the three N-oxides was active at 4 μM concentration, being less active than the parent base 2 by a factor of 40.

著者

板谷 泰助 小川 和男 松本 浩郎 渡辺 朝子

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.28, no.8, pp.2522-2527, 1980-08-25 (Released:2008-03-31)

参考文献数

10

被引用文献数

3 5

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The reactions of N, N, 9-trialkyladenines (II) with alkyl halides in N, N-dimethylacetamide gave N, N, 3, 9-tetraalkyladeninium halides (IV) in good yields. N, N, 3-Trialkyl-adenines (III) underwent the alkylation more smoothly to provide an alternative synthesis of IV.

著者

小川 和男 西井 正廣 野原 富士夫 斎藤 徹 板谷 泰助 藤井 澄三

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.40, no.3, pp.612-616, 1992-03-25 (Released:2008-03-31)

参考文献数

46

被引用文献数

2 8

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A detailed account is given of the first chemical synthesis of hypoxanthine 7-N-oxide (5), which started from coupling of 6-chloro-5-nitro-4(3H)-pyrimidinone (7) with N-(4-methoxybenzyl)phenacylamine, generated in situ from the hydrochloride (8), and proceeded through cyclization of the resulting phenacylaminopyrimidinone (9) and removal of the 4-methoxybenzyl group. The results of catalytic hydrogenolysis, methylation followed by catalytic hydrogenolysis, and rearrangement under acidic conditions of 5 supported the correctness of the assigned structure. An ultraviolet spectroscopic approach suggested that the neutral species of 5 exists in H2O mainly as the N(7)-OH tautomer (21). In the in vitro bioassay of antileukemic activity against murine L5178Y cells, 5 was weakly cytotoxic, with IC50 of 100μg/ml. It did not show any antimicrobial activity even at 1000μg/ml. None of the 9-(4-methoxybenxyl) (11) and O-methyl (12, 13, and 14) derivatives was found to be antiieukemic or antimicrobial.