Potential bile acid metabolites. XVIII. Synthesis of stereoisomeric 3,6,12 alpha-trihydroxy-5 beta-cholanoic acids.
Two new 6-hydroxylated bile acids, 3 beta, 6 alpha, 12 alpha- and 3 beta, 6 beta, 12 alpha-trihydroxy-5 beta-cholanoic acids, were synthesized from deoxycholic acid. In addition, their C-3 epimers, 3 alpha, 6 alpha, 12 alpha- and 3 alpha, 6 beta, 12 alpha-trihydroxy acids, were prepared by a new route. The principal reactions used were 1) 6 beta-hydroxylation of 3-methoxy-3,5-dienes with m-chloroperbenzoic acid in aqueous dioxane; 2) catalytic hydrogenation of the resulting 6 beta-hydroxy-3-oxo-4-enes to the 6 beta-hydroxy-3-oxo-5 beta compounds with palladium on calcium carbonate catalyst in ethanol; and 3) stereoselective reduction of appropriate 3-oxo derivatives with potassium tri-sec-butylborohydride and tert-butylamine-borane complex. The thin-layer chromatographic, gas-liquid chromatographic, and high performance liquid chromatographic mobilities, and 1H- and 13C-nuclear magnetic resonance spectroscopic data of the four stereoisomers are presented. With this work all the 6-hydroxylated derivatives of lithocholic, deoxycholic, chenodeoxycholic, ursodeoxycholic, and cholic acids in the 5 beta series are now known and have been synthesized.
Iida
T
T
College of Engineering, Nihon University, Fukushima-ken, Japan.
Tamaru
T
T
Chang
F C
FC
Goto
J
J
Nambara
T
T
D001647:Bile Acids and Salts / Q000378:metabolism*; D002793:Cholic Acids / Q000138:chemical synthesis*; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism
D001647:Bile Acids and Salts; D002793:Cholic Acids; C028410:3,6,12-trihydroxycholanoic acid