3,4-Seco-12α-hydroxy-5β-cholan-3,4,24-trioic Acid, a Novel Secondary Bile Acid: Isolation from the Bile of the Common Ringtail Possum (Pseudocheirus peregrinus) and Chemical Synthesis

The major bile acids present in gallbladder bile of the common ringtail possum (Pseudocheirus peregrinus), an Australian marsupial, were isolated by preparative HPLC and identified by NMR and by comparison with synthetic standards. The major compound present (52%) was 3α,12α-dihydroxy-7-oxo-5β-cholan-24-oic acid (7-oxodeoxycholic acid), about three fourths conjugated with taurine. Also present was 3α,7β,12α-trihydroxy-5β-cholan- 24-oic acid (20%; ursocholic acid) largely in unconjugated form. In addition, 3,4-seco-12α-hydroxy-5β-cholan-3,4,24- trioic acid was present in unconjugated form and constituted 8% of biliary bile acids. Proof of the structure of this novel 3,4-seco acid was obtained by its chemical synthesis from deoxycholic acid via an intermediary 3β,4β-dihydroxy derivative that was then oxidatively cleaved with sodium periodate. As all primary bile acids have a hydroxyl or oxo substituent at C-7, the absence of such in the seco-bile acid suggests that it is a secondary bile acid, synthesized by bacterial enzymes present in the intestine.