Isolation and chemical synthesis of a major, novel biliary bile acid in the common wombat (Vombatus ursinus): 15α-hydroxylithocholic acid

The major bile acids present in the gallbladder bile of the common Australian wombat (Vombatus ursinus) were isolated by preparative HPLC and identified by NMR as the taurine N-acylamidates of chenodeoxycholic acid (CDCA) and 15α-hydroxylithocholic acid (3α,15α-dihydroxy-5β-cholan-24-oic acid). Taurine-conjugated CDCA constituted 78% of biliary bile acids, and (taurine-conjugated) 15α-hydroxylithocholic acid constituted 11%. Proof of structure of the latter compound was obtained by its synthesis from CDCA via a Δ14 intermediate. The synthesis of its C-15 epimer, 15β-hydroxylithocholic acid (3α,15β-dihydroxy-5β-cholan-24-oic acid), is also reported. The taurine conjugate of 15α-hydroxylithocholic acid was synthesized and shown to have chromatographic and spectroscopic properties identical to those of the compound isolated from bile. It is likely that 15α-hydroxylithocholic acid is synthesized in the wombat hepatocyte by 15α-hydroxylation of lithocholic acid that was formed by bacterial 7α-dehydroxylation of CDCA in the distal intestine. Thus, the wombat appears to use 15α-hydroxylation as a novel detoxification mechanism for lithocholic acid.