Chemical synthesis of (22E)-3 alpha,6 beta,7 beta-trihydroxy-5 beta-chol-22-en-24-oic acid and its taurine and glycine conjugates: a major bile acid in the rat.
A method for the synthesis of Delta(22)-beta-muricholic acid (Delta(22)-beta-MCA), (22E)-3 alpha,6 beta,7 beta-trihydroxy-5 beta-chol-22-en-24-oic acid, and its taurine and glycine conjugates (Delta(22)-beta-muricholyltaurine and Delta(22)-beta-muricholylglycine) is described. The key intermediate, 3 alpha,6 beta,7 beta-triformyloxy-23,24-dinor-5 beta-cholan-22-al, was prepared from beta-muricholic acid (beta-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) Delta(22)-beta-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 Delta(22)-beta-MCA. These synthetic reference compounds are now available for investigation of the metabolism of beta-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-(2)H or (3)H-beta-MCA.
Kakiyama
Genta
G
Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo 156-8550, Japan.
Iida
Takashi
T
Yoshimoto
Atsushi
A
Goto
Takaaki
T
Mano
Nariyasu
N
Goto
Junichi
J
Nambara
Toshio
T
Hagey
Lee R
LR
Hofmann
Alan F
AF
D000818:Animals; D001647:Bile Acids and Salts / Q000138:chemical synthesis* / Q000737:chemistry; D019826:Cholic Acid / Q000138:chemical synthesis* / Q000737:chemistry; D002793:Cholic Acids; D005998:Glycine / Q000737:chemistry*; D015394:Molecular Structure; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013654:Taurine / Q000737:chemistry*
C493044:(22E)-3 alpha,6 beta,7 beta-trihydroxy-5 beta-chol-22-en-24-oic acid; D001647:Bile Acids and Salts; D002793:Cholic Acids; D013654:Taurine; D019826:Cholic Acid; D005998:Glycine