Chemical Synthesis of the Epimeric (23R)- and (23S)-Fluoro Derivatives of Bile Acids via Horner-Wadsworth-Emmons Reaction.
Lipids
; 50(9): 919-26, 2015 Sep.
Article
en En
| MEDLINE
| ID: mdl-26193795
ABSTRACT
A method for the synthesis of two (23R)- and (23S)-epimeric pairs of 23-fluoro-3α,7α,12α-trihydroxy-5ß-cholan-24-oic acid and 23-fluoro-3α,7α-dihydroxy-5ß-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.
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Bases de datos:
MEDLINE
Asunto principal:
Ácidos y Sales Biliares
Idioma:
En
Revista:
Lipids
Año:
2015
Tipo del documento:
Article
País de afiliación:
Japón