Studies on Morphinan Derivatives. II. The Synthesis of d-3-Methyl-N-methylmorphinan, a New Antitussive

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概要

• 論文の詳細を見る

• N-Methyl-5,6,7,8-tetrahydroisoquinolinium bromide (IV) was reacted with p-methylbenzyl chloride by means of Grignard reaction to obtain 1-(4-methylbenzyl)-2-methyl-1,2,5,6,7,8-hexahydroisoquinoline (V). V was immediately reduced to 1-(4-methylbenzyl)-2-methyl-1,2,3,4,5,6,7,8-octahydroisoquinoline (VI) with sodium borohydride. VI was resolved by means of L(+)-tartaric acid. d, l and dl-VI were cyclized to d, l and dl-3-methyl-N-methylmorphinan (II), respectively, by treating them with 85% phosphoric acid at 135-150°. Several 3-methyl-N-alkyl and alkenyl-morphinan derivatives were synthesized from 3-methylmorphinan (VIII), which was prepared by demethylation of II, by treating it with alkyl and alkenyl halides. Antitussive activities of d-II were 1.5 times as strong as that of dextrometorphan (Ib), and a toxicity of d-II was lower than that of Ib. Furthermore, d-II did not form any physical dependence.

• 公益社団法人日本薬学会の論文
• 1972-08-25

著者

• 犬飼 紀喜

  Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.,

• 村上 増雄

  Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.

• 井田 昶

  Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.

• 河原 茂実

  山之内製薬株式会社中央研究所

• 岩本 英徳

  Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.

• 岩本 英徳

  Central Research Laboratories Yamanouchi Pharmaceutical Co. Ltd.

• 河原 茂実

  Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.

• 長野 憲明

  Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.

• 井田 昶

  Central Research Laboratories Yamanouchi Pharmaceutical Co. Ltd.

• 犬飼 紀喜

  Tsukuba Research Laboratories Yamanouchi Pharmaceutical Co. Ltd.

• 長野 憲明

  Central Research Laboratories Yamanouchi Pharmaceutical Co. Ltd.

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