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

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

瀬沼 勝 柴崎 昌隆 西本 茂 柴田 恵次郎 岡村 公生 伊達 忠正

出版者

公益社団法人日本薬学会

雑誌

Chem. Pharm. Bull. (ISSN:00092363)

巻号頁・発行日

vol.37, pp.3204-3208, 1989

被引用文献数

1

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Practical resolution of (2RS, 3RS)-2-hydroxy-3-(4-methoxyphenyl)-3-(2-nitrophenylthio)propionic acid (2) was examined by the use of several basic amino acids. L-Lysine was found to be the most effective resolving agent to obtain (+)-(2S, 3S)-2,a key intermediate for the synthesis of diltiazem (1). This new method should be applicable to the industrial production of 1 in view of the simplicity of the procedure, the ready availability of L-lysine, and the high yield of the desired isomer. The absolute stereochemistry of (+)-2 was determined to be 2S, 3S by X-ray crystallographic analysis.

著者

瀬沼 勝 藤井 武彦 瀬戸 正彦 岡村 公生 伊達 忠正 絹巻 明生

出版者

公益社団法人日本薬学会

雑誌

Chemical & pharmaceutical bulletin (ISSN:00092363)

巻号頁・発行日

vol.38, no.4, pp.882-887, 1990-04-25

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The direct resolution of (3aRS, 6SR, 6aSR)-1,3-dibenzyl-6-hydroxy-3,3a, 6,6a-tetrahydro-1H-furo[3,4-d]imidazole-2,4-dione [(±)-9], a key intermediate for biotin, with optically active amines was examined. Reaction of (±)-9 with cinchonidine readili gave the cinchonidine salt of the (4S, 5R)-aldehyde-carboxylic acid (12), acidification of which gave (3aS.6R, 6aR)-9,convertible to biothin. N-alkyl-D-glucamines (14) were also found to be effective resolving agents for (±)-9 applicable for industrial use. Reutilizatin of the unwanted epimer [(3aR, 6S, 6aS)-9] was effected by facile oxidation to the meso-diacid (3) with sodium chlorite.