Bile acids, tertiary

C24 bile acids are synthesised in the liver from cholesterol. The bacterial enzyme 7-a dehydroxylase converts CDCA into LCA and converts CA into DCA. UDCA a tertiary bile acid is also shown. 

The tertiary bile acids are formed in the liver as well as in the gut. (s. fig. 3.3) Intestinally absorbed lithocholic acid is enzymatically converted to sulpholitho-cholic acid in the liver. Ketolithocholic acid is transformed to (hypercholeretic) ursodeoxycholic acid in both the intestine and the liver. When passing through the canaliculi, UDC is partly reabsorbed by epithelial cells and returned to the liver via the blood circulation (= cholehepatic shunt). (41) The latter is chemically and structurally identical to chenodeoxycholic acid, of which it is deemed to be the 7P-epimer ... 

Another steric factor becomes important when working with bile acids or other A/B cis-(5p)-steroids 14. Despite the fact that the C9 —H bond is the most electronically favored for electrophilic substitution, ring A which is perpendicular to the steroidal plane blocks the access to it. The fluorine, which has to approach with a solvent molecule, attacks the other tertiary sites at C5, Cl 4 and C17.42... 

MIESCHER DEGRADATION. Adaptation of the Barbier-Wieland carboxylic acid degradation to pcrmil simultaneous elimination of three carbon atoms, as in degradation of the bile acid side chain to the methyl ketone stage. Conversion of the methyl ester of the bile acid to the tertiary alcohol, followed by dehydration, bromination. dehydrohalogenatinn, and oxidation of the diene yields die required degraded ketone. 

Steroids, bile acids, and similar compounds pose certain problems when they require to be derivatized for separation by GC. The hydroxyl groups in the respective structures differ greatly in their reaction rate, which will depend on their nature (whether they are primary, secondary, or tertiary) and also, to a certain extent, on their steric environment. 

GC-MS analysis of urine and bile extracts showed the major eliminated metabolites of IPBP to be ring hydroxylated derivatives of the tertiary carbinol and the propionic acid. Minor amounts of ring hydroxylated atrolactic acid and the primary carbinol were also found (Fig. 2). While the atrolactic acid was found to be a major circulating matabolite no detectable quantity of this acid could be found in the urine or bile. The failure to detect the primary carbinol in the plasma and the detection of only small eliminated quantities of its ring hydroxylated derivative implied its rapid metabolic conversion to the propionic acid. Other minor metabolites included 2- -biphenylyl-l,2-propranediol a possible precursor for the atrolactic acid. 

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