title: Isolation and chemical synthesis of a major, novel biliary bile acid in the common wombat (Vombatus ursinus): 15alpha-hydroxylithocholic acid.
abstract: 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 15alpha-hydroxylithocholic acid (3alpha,15alpha-dihydroxy-5beta-cholan-24-oic acid). Taurine-conjugated CDCA constituted 78% of biliary bile acids, and (taurine-conjugated) 15alpha-hydroxylithocholic acid constituted 11%. Proof of structure of the latter compound was obtained by its synthesis from CDCA via a Delta14 intermediate. The synthesis of its C-15 epimer, 15beta-hydroxylithocholic acid (3alpha,15beta-dihydroxy-5beta-cholan-24-oic acid), is also reported. The taurine conjugate of 15alpha-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 15alpha-hydroxylithocholic acid is synthesized in the wombat hepatocyte by 15alpha-hydroxylation of lithocholic acid that was formed by bacterial 7alpha-dehydroxylation of CDCA in the distal intestine. Thus, the wombat appears to use 15alpha-hydroxylation as a novel detoxification mechanism for lithocholic acid.
authors.affiliation: Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajosui, Setagaya, Tokyo 156-8550, Japan.
authors.forename: Genta
authors.initials: G
authors.lastname: Kakiyama
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tamegai
authors.forename: Takashi
authors.initials: T
authors.lastname: Iida
authors.forename: Kuniko
authors.initials: K
authors.lastname: Mitamura
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ikegawa
authors.forename: Takaaki
authors.initials: T
authors.lastname: Goto
authors.forename: Nariyasu
authors.initials: N
authors.lastname: Mano
authors.forename: Junichi
authors.initials: J
authors.lastname: Goto
authors.forename: Peter
authors.initials: P
authors.lastname: Holz
authors.forename: Lee R
authors.initials: LR
authors.lastname: Hagey
authors.forename: Alan F
authors.initials: AF
authors.lastname: Hofmann
mesh_terms: D000818:Animals; D002793:Cholic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid; D008095:Lithocholic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification; D008394:Marsupialia / Q000378:metabolism*