Chemical synthesis of (22E)-3α,6β,7β-trihydroxy-5β-chol-22-en-24-oic acid and its taurine and glycine conjugates

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

Journal of Lipid Research (Mar 2004)

Chemical synthesis of (22E)-3α,6β,7β-trihydroxy-5β-chol-22-en-24-oic acid and its taurine and glycine conjugates

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

Affiliations

Genta Kakiyama: Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo 156-8550, Japan; Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan; Department of Medicine, University of California, San Diego, La Jolla, California 92093-0813
Takashi Iida: Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo 156-8550, Japan; Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan; Department of Medicine, University of California, San Diego, La Jolla, California 92093-0813
Atsushi Yoshimoto: Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo 156-8550, Japan; Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan; Department of Medicine, University of California, San Diego, La Jolla, California 92093-0813
Takaaki Goto: Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo 156-8550, Japan; Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan; Department of Medicine, University of California, San Diego, La Jolla, California 92093-0813
Nariyasu Mano: Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo 156-8550, Japan; Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan; Department of Medicine, University of California, San Diego, La Jolla, California 92093-0813
Junichi Goto: Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo 156-8550, Japan; Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan; Department of Medicine, University of California, San Diego, La Jolla, California 92093-0813
Toshio Nambara: Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo 156-8550, Japan; Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan; Department of Medicine, University of California, San Diego, La Jolla, California 92093-0813
Lee R. Hagey: Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo 156-8550, Japan; Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan; Department of Medicine, University of California, San Diego, La Jolla, California 92093-0813
Alan F. Hofmann: Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo 156-8550, Japan; Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan; Department of Medicine, University of California, San Diego, La Jolla, California 92093-0813

Journal volume & issue: Vol. 45, no. 3
pp. 567 – 573

Abstract

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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 Δ22-β-muricholylglycine) is described. The key intermediate, 3α,6β,7β-triformyloxy-23,24-dinor-5β-cholan-22-al, 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.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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