Lipids

, Volume 50, Issue 9, pp 919–926 | Cite as

Chemical Synthesis of the Epimeric (23R)- and (23S)-Fluoro Derivatives of Bile Acids via Horner–Wadsworth–Emmons Reaction

  • Kaoru Omura
  • Yuuki Adachi
  • Yuuki Kobayashi
  • Shoutaro Sekiguchi
  • Biao Zhou
  • Takashi Iida
Methods
  • 237 Downloads

Abstract

A method for the synthesis of two (23R)- and (23S)-epimeric pairs of 23-fluoro-3α,7α,12α-trihydroxy-5β-cholan-24-oic acid and 23-fluoro-3α,7α-dihydroxy-5β-cholan-24-oic acid is described. The key intermediates, 23,24-dinor-22-aldehyde peracetates were prepared from cholic and chenodeoxycholic acids via the 24-nor-22-ene, 24-nor-22ξ,23-epoxy, and 23,24-dinor-22-aldehyde derivatives. The Horner–Wadsworth–Emmons reaction of the 23,24-dinor-22-aldehydes using triethyl 2-fluoro-2-phosphonoacetate in the presence of LiCl and 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), and subsequent hydrogenation of the resulting 23ξ-fluoro-22-ene ethyl esters, followed by hydrolysis, gave a mixture of the epimeric (23R)- and (23S)-fluorinated bile acids which were resolved efficiently by preparative RP-HPLC. The stereochemical configuration of the fluorine atom at C-23 in the newly synthesized compounds was confirmed directly by the X-ray crystallographic data. The 1H and 13C NMR spectral differences between the (23R)- and (23S)-epimers were also discussed.

Keywords

Bile acid Epimeric (23R)-/(23S)-fluoro-bile acids Horner–Wadsworth–Emmons reaction α-Fluoro-α,β-unsaturated esterification 

Abbreviations

MMO

4-Methylmorpholine N-oxide

DBU

1,8-Diazabicyclo[5,4,0]undec-7-ene

NMR

Nuclear magnetic resonance

HPLC

High-performance liquid chromatography

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Copyright information

© AOCS 2015

Authors and Affiliations

  • Kaoru Omura
    • 1
  • Yuuki Adachi
    • 1
  • Yuuki Kobayashi
    • 1
  • Shoutaro Sekiguchi
    • 1
  • Biao Zhou
    • 1
  • Takashi Iida
    • 1
  1. 1.Department of Chemistry, College of Humanities and SciencesNihon UniversitySetagayaJapan

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