Stereospecific synthesis and two-dimensional 1H-NMR investigation of isoursocholic acid.
This report describes the chemical synthesis of isoursocholic acid (3 beta, 7 beta, 12 alpha-trihydroxy-5 beta-cholanoic acid) from its corresponding 3 alpha-analog. The method consists of refluxing a mixture of ursocholic acid, triphenylphosphine, and diethyl azodicarboxylate in benzene solution with an acid such as formic acid. The sterically pure ester (3 beta-formate) so formed after saponification with LiOH-aqueous methanol then allowed an easy access to the epimer of the starting acid. Large scale preparative separation and purification of the final product and synthetic intermediates were accomplished by flash column chromatography of their methyl ester derivatives. Structural assignment of the isourscholic acid molecule was confirmed by complete analysis of proton NMR spectra using 2-D NMR correlation experiments which rigorously established the (3 beta/3 alpha) and (7 beta/7 alpha) hydroxyl configurations in the isoursocholic and ursocholic acids. It is suggested that the isoursocholic acid will be useful as a reference compound and as a substrate in studies dealing with the hepatic inversion of the 3 beta-hydroxy group.
Dayal
B
B
Department of Medicine, UMDNJ-New Jersey Medical School, Newark 07103.
Salen
G
G
D001647:Bile Acids and Salts / Q000737:chemistry; D002247:Carbon Isotopes; D002793:Cholic Acids / Q000138:chemical synthesis*; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry; D015394:Molecular Structure; D013237:Stereoisomerism
D001647:Bile Acids and Salts; D002247:Carbon Isotopes; D002793:Cholic Acids; C030712:ursocholic acid