7 beta-hydroxy bile alcohols: facile synthesis and 2D 1H NMR studies of 5 beta-cholestane-3 alpha, 7 beta, 12 alpha, 25-tetrol.
A rapid and easily performed procedure for the synthesis of 5 beta-cholestane-3 alpha, 7 beta, 12 alpha, 25-tetrol by means of an efficient homologation sequence of the intermediate, 3 alpha, 7 beta, 12 alpha-triformyloxy-24-oxo-25-diazo-25-homo-5 beta-cholane is described. The reaction sequence involved treating the intermediate, alpha-diazoketone in methanol with 3% AgNO3 or Ag2O, anhydrous Na2CO3, Na2S2O/H2O resulting in the formation of homoursocholic acid in high yield. Esterification of the homoursocholic acid in methanol containing a catalytic amount of methanesulfonic acid under microwave irradiation conditions gave methyl homourscholate. The subsequent treatment of methyl homoursocholate with methyl magnesium iodide provided 5 beta-cholestane-3 alpha, 7 beta, 12 alpha, 25-tetrol in 88% yield. The products and synthetic intermediates prepared in these studies were fully characterized by the results of 1D and 2D NMR, and high-resolution mass spectral studies. These studies will help in further investigation of the defect of cholic acid biosynthesis in patients with cerebrotendinous xanthomatosis (CTX) as well as other inborn errors of bile acid metabolism.
Dayal
B
B
Department of Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, USA.
Ertel
N H
NH
Padia
J
J
Rapole
K R
KR
Salen
G
G
D001647:Bile Acids and Salts / Q000378:metabolism*; D002777:Cholestanols / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D016339:Spectrometry, Mass, Fast Atom Bombardment; D019294:Xanthomatosis, Cerebrotendinous / Q000378:metabolism*
D001647:Bile Acids and Salts; D002777:Cholestanols; C010556:cholestane-3,7,12,25-tetrol