Practical syntheses of enantiomerically pure key intermediates of opioid receptor-like 1 (ORL1) antagonists

Takashi Yoshizumi, Akio Ohno, Tomohiro Tsujita, Hirobumi Takahashi, Osamu Okamoto, Ichiro Hayakawa, Hideo Kigoshi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Practical syntheses of enantiomerically pure key intermediates of opioid receptor-like 1 (ORL1) antagonists are described. Our synthetic methodology features the preparation of multigram quantities of seven-membered key intermediate (-)-3 and six-membered one (-)-4 without the use of toxic tin reagents. In the case of (-)-3, the key step involved diastereoselective reduction using a sterically hindered reducing reagent. Our methodology allows for facile scale-up to afford the products in multigram quantities [in the case of (-)-4, >100-g quantities). These convenient approaches facilitate structure-activity relationship studies including in vivo cardiovascular adverse effects.

Original languageEnglish
Article numberF22608SS
Pages (from-to)1153-1162
Number of pages10
JournalSynthesis
Issue number7
DOIs
Publication statusPublished - Apr 1 2009
Externally publishedYes

Keywords

  • Asymmetric synthesis
  • Cycloalkano[1,2-b]pyridines
  • Multigram-scale preparation
  • ORL1 antagonist
  • Stereoselective reduction

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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    Yoshizumi, T., Ohno, A., Tsujita, T., Takahashi, H., Okamoto, O., Hayakawa, I., & Kigoshi, H. (2009). Practical syntheses of enantiomerically pure key intermediates of opioid receptor-like 1 (ORL1) antagonists. Synthesis, (7), 1153-1162. [F22608SS]. https://doi.org/10.1055/s-0028-1087989