An Improved Synthesis of the New Angiotensin Converting Enzyme Inhibitor CV-5975 via a Chemoenzymatic Process(Organic,Chemical)

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概要

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• A chemoenzymatic synthesis of the new angiotensin converting enzyme inhibitor CV-5975 (1) is described. The optically active key intermediate for the synthesis of 1, ethyl (R-6-(1-benzyloxycarbonyl-4-piperidyl)-2-hydroxyhexanoate ((R)-4), was prepared by kinetic resolution of the racemic α-hydroxyester ((RS)-4) with a lipase and also by asymmetric reduction of the α-oxoester (3) with baker's yeast, The enantiomeric excess (ee) of the a-hydroxyester ((R)-4) produced by these enzymatic procedures exceeded 60%. This optically active alcohol ((R)-4) was converted to its mesylate ((R)-5), which was then subjected to S_N2 reaction with the aminobenzothiazepine derivative (2) followed by deprotection to yield 1.

• 公益社団法人日本薬学会の論文
• 1987-06-25

著者

• 伊藤 克己

  Pharmaceutical Research Laboratories Iii Pharmaceutical Research Division Takeda Chemical Industries

• 郡 正城

  Pharmaceutical Research Laboratories, Takeda Chemical Industries, Ltd.,

• 伊藤 克己

  Central Research Division, Takeda Chemical Industries, Ltd.,

• 郡 正城

  Central Research Division, Takeda Chemical Industries, Ltd.,

• 杉原 弘貞

  Central Research Division, Takeda Chemical Industries, Ltd.,

• 伊藤 克巳

  武田薬品工業

• 伊藤 克已

  Central Research Division Takeda Chemical Industries Ltd.

• 郡 正城

  Pharmaceutical Research Laboratories Takeda Chemical Industries Ltd.

• 杉原 弘貞

  Pharamaceutical Research Laboratories I Pharmaceutical Research Division Takeda Chemical Industries

• 杉原 弘貞

  Central Research Division Takeda Chemical Industries. Ltd.

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