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

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.