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

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.

DOI: 10.1007/s11745-015-4050-8

Extracted Key Phrases

7 Figures and Tables

Cite this paper

@article{Omura2015ChemicalSO, title={Chemical Synthesis of the Epimeric (23R)- and (23S)-Fluoro Derivatives of Bile Acids via Horner–Wadsworth–Emmons Reaction}, author={Kaoru Omura and Yuuki Adachi and Yuuki Kobayashi and Shoutaro Sekiguchi and Biao Zhou and Takashi Iida}, journal={Lipids}, year={2015}, volume={50}, pages={919-926} }