title: 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 (1)H and (13)C NMR spectral differences between the (23R)- and (23S)-epimers were also discussed.
authors.affiliation: Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo, 156-8550, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Omura
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Adachi
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Shoutaro
authors.initials: S
authors.lastname: Sekiguchi
authors.forename: Biao
authors.initials: B
authors.lastname: Zhou
authors.forename: Takashi
authors.initials: T
authors.lastname: Iida
mesh_terms: D001647:Bile Acids and Salts / Q000138:chemical synthesis* / Q000737:chemistry*; D002635:Chenodeoxycholic Acid / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy
chemical_list: D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid