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 2009
Externally publishedYes

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Opioid Receptors
Tin
Poisons

Keywords

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

ASJC Scopus subject areas

  • Organic Chemistry
  • Catalysis

Cite this

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

Practical syntheses of enantiomerically pure key intermediates of opioid receptor-like 1 (ORL1) antagonists. / Yoshizumi, Takashi; Ohno, Akio; Tsujita, Tomohiro; Takahashi, Hirobumi; Okamoto, Osamu; Hayakawa, Ichiro; Kigoshi, Hideo.

In: Synthesis, No. 7, F22608SS, 04.2009, p. 1153-1162.

Research output: Contribution to journalArticle

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, no. 7, F22608SS, pp. 1153-1162. https://doi.org/10.1055/s-0028-1087989
Yoshizumi, Takashi ; Ohno, Akio ; Tsujita, Tomohiro ; Takahashi, Hirobumi ; Okamoto, Osamu ; Hayakawa, Ichiro ; Kigoshi, Hideo. / Practical syntheses of enantiomerically pure key intermediates of opioid receptor-like 1 (ORL1) antagonists. In: Synthesis. 2009 ; No. 7. pp. 1153-1162.
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