Potential Bile Acid Metabolites. XV. : Synthesis of 4β-Hydroxylated Bile Acids; Unique Bile Acids in Human Fetal Bile

Abstract

The 4β-hydroxylated derivatives of lithocholic, deoxycholic, chenodeoxycholic, and cholic acids were synthesized from their respective parent compounds. The principal reactions employed were 1) β-face cis-dihydroxylation of Δ³ intermediates with osmium tetroxide-N-methylmorpholine N-oxide, 2) selective cathylation of vicinal 3β, 4β-diols followed by oxidation of the resulting 4β-monocathylates, or direct selective oxidation at C-3 of 3β, 4β-diols with pyridinium chlorochromate, and 3) stereoselective reduction of the 3-oxo compounds with tert-butylamine-borane complex. The results of analysis of the prepared 4β-hydroxylated bile acids with a diequatorial trans-glycol structure and their 3β-epimers by proton and carbon-13 nuclear magnetic resonance spectroscopies are briefly discussed along with the mass spectrometric properties.