Chemical synthesis of (22E)-3α,6β,7β-trihydroxy-5β -chol-22-en-24-oic acid and its taurine and glycine conjugates: A major bile acid in the rat

Genta Kakiyama, Takashi Iida, Atsushi Yoshimoto, Takaaki Goto, Nariyasu Mano, Junichi Goto, Toshio Nambara, Lee R. Hagey, Alan F. Hofmann

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

A method for the synthesis of Δ22-β-muricholic acid (Δ22-β-MCA), (22E)-3α,6β,7β -trihydroxy-5β-chol-22-en-24-oic acid, and its taurine and glycine conjugates (Δ22-β-muricholyltaurine and Δ 22-β-muricholylglycine) is described. The key intermediate, 3α,6β,7β-triformyloxy-23,24-dinor-5β-cholan-22-a1, was prepared from β-muricholic acid (β-MCA) via the 24-nor-22-ene and 24-nor-22,23-diol derivatives. Wittig reaction of the aldehyde with (carbomethoxymethylene) triphenylphosphorane and subsequent hydrolysis gave (unconjugated) Δ22-β-MCA. Condensation reaction of the unconjugated acid with taurine or glycine methyl ester using diethylphosphorocyanide yielded the naturally occurring taurine or glycine conjugate (N-acylamidate) of Δ22-β-MCA. These synthetic reference compounds are now available for investigation of the metabolism of β-MCA by bacterial and hepatic enzymes in the rat and should also be useful as substrates for reductive deuteration or tritiation to give the 22,23-2H or 3H-β-MCA.

Original languageEnglish
Pages (from-to)567-573
Number of pages7
JournalJournal of lipid research
Volume45
Issue number3
DOIs
Publication statusPublished - 2004 Mar

Keywords

  • Glyco-Δ-β -muricholic acid
  • Tauro-Δ-β-muricholic acid
  • Unsaturated bile acid
  • Δ-β-muricholylglycine
  • Δ-β-muricholyltaurine

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Chemical synthesis of (22E)-3α,6β,7β-trihydroxy-5β -chol-22-en-24-oic acid and its taurine and glycine conjugates: A major bile acid in the rat'. Together they form a unique fingerprint.

Cite this