Chemical Synthesis of Uncommon Natural Bile Acids: The 9α-Hydroxy Derivatives of Chenodeoxycholic and Lithocholic Acids

• Iida Takashi

  College of Humanities & Sciences, Nihon University

• Namegawa Kazunari

  College of Humanities & Sciences, Nihon University

• Nakane Naoya

  College of Humanities & Sciences, Nihon University

• Iida Kyoko

  College of Humanities & Sciences, Nihon University

• Hofmann Alan Frederick

  Department of Medicine, University of California at San Diego

• Omura Kaoru

  College of Humanities & Sciences, Nihon University

抄録

The chemical synthesis of the 9α-hydroxy derivatives of chenodeoxycholic and lithocholic acids is reported. For initiating the synthesis of the 9α-hydroxy derivative of chenodeoxycholic acid, cholic acid was used; for the synthesis of the 9α-hydroxy derivative of lithocholic acid, deoxycholic acid was used. The principal reactions involved were (1) decarbonylation of conjugated 12-oxo-Δ⁹⁽¹¹⁾-derivatives using in situ generated monochloroalane (AlH₂Cl) prepared from LiAlH₄ and AlCl₃, (2) epoxidation of the deoxygenated Δ⁹⁽¹¹⁾-enes using m-chloroperbenzoic acid catalyzed by 4,4′-thiobis-(6-tert-butyl-3-methylphenol), (3) subsequent Markovnikov 9α-hydroxylation of the Δ⁹⁽¹¹⁾-enes with AlH₂Cl, and (4) selective oxidation of the primary hydroxyl group at C-24 in the resulting 3α,9α,24-triol and 3α,7α,9α,24-tetrol to the corresponding C-24 carboxylic acids using sodium chlorite (NaClO₂) in the presence of a catalytic amount of 2,2,6,6-tetramethylpiperidine 1-oxyl free radical (TEMPO) and sodium hypochlorite (NaOCl). The ¹H- and ¹³C-NMR spectra are reported. The 3α,7α,9α-trihydroxy-5β-cholan-24-oic acid has been reported to be present in the bile of the Asian bear, and its 7-deoxy derivative is likely to be a bacterial metabolite. These bile acids are now available as authentic reference standards, permitting their identification in vertebrate bile acids.

収録刊行物

• ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ

  ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 64 (9), 1397-1402, 2016

  公益社団法人 日本薬学会

キーワード

• 9α-hydroxy-bile acid
• C-9 5β-steroid hydroxylation
• decarbonylation
• monochloroalane
• Markovnikov-hydroxylation
• 2,2,6,6-tetramethylpiperidine 1-oxyl free radical

詳細情報

• CRID: 1390001204179059072
• NII論文ID: 130005261594
• NII書誌ID: AA00602100
• DOI: 10.1248/cpb.c16-00247
• ISSN: 13475223
• ISSN: 00092363
• NDL書誌ID: 027565598
• PubMed: 27319285
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027565598
• Web Site: https://www.jstage.jst.go.jp/article/cpb/64/9/64_c16-00247/_pdf
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可