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  • 标题:Stereo-Selective Preparation of Teneraic Acid, trans-(2S,6S)-Piperidine-2,6-dicarboxylic Acid, via Anodic Oxidation and Cobalt-Catalyzed Carbonylation
  • 本地全文:下载
  • 作者:Yusuke Amino ; Seiichi Nishi ; Kunisuke Izawa
  • 期刊名称:Chemical and Pharmaceutical Bulletin
  • 印刷版ISSN:0009-2363
  • 电子版ISSN:1347-5223
  • 出版年度:2017
  • 卷号:65
  • 期号:9
  • 页码:854-861
  • DOI:10.1248/cpb.c17-00391
  • 语种:English
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    Teneraic acid (piperidine-2,6-dicarboxylic acid) is a naturally occurring imino acid that comprises three stereoisomers due to its two asymmetric centers at C2 and C6. The configuration of natural teneraic acid is reported to correspond to trans -(2 S ,6 S ). However, a few studies are focused on the stereospecific synthesis of trans -(2 S ,6 S )-teneraic acid. The present study investigates a convenient synthetic method that includes regiospecific anodic oxidation and stereospecific cobalt-catalyzed carbonylation to obtain trans -(2 S ,6 S )-teneraic acid. Methyl ( S )- N -benzoyl-α-methoxypipecolate, the key intermediate that displays a structure that corresponds to an intermediate ( N -α-hydroxyalkyl amide) of intramolecular amidocarbonylation, was obtained via an anodic oxidation of methyl ( S )- N -benzoylpipecolate. Subsequently, cobalt-catalyzed carbonylation converted the methyl ( S )- N -benzoyl-α-methoxypipecolate to trans -(2 S ,6 S )- N -benzoyl-teneraic acid dimethyl ester in good optical purity (>95% enantiomeric excess (ee)) and modest yield (63%). Finally, de-protection occurred via acidic hydrolysis to obtain trans -(2 S ,6 S )-teneraic acid. The stereochemistry of synthesized teneraic acid was confirmed as corresponding to trans -(2 S ,6 S ) by comparing its physical properties with those of a cis-meso -isomer and those of a trans -(2 S ,6 S )-isomer that were reported in previous studies.

  • 关键词:teneraic acid;piperidine-2,6-dicarboxylic acid;stereoisomer;amidocarbonylation;anodic oxidation;carbonylation
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