title: Improved chemical synthesis, X-ray crystallographic analysis, and NMR characterization of (22R)-/(22S)-hydroxy epimers of bile acids.
abstract: We report an improved synthesis of the (22R)- and (22S)-epimers of 3α,7α,12α,22-tetrahydroxy-5β-cholan-24-oic acid and 3α,7α,22-trihydroxy-5β-cholan-24-oic acid from cholic acid (CA) and chenodeoxycholic acid (CDCA), respectively. The principal reactions involved were as follows: (1) oxidative decarboxylation of the bile acid peracetates with lead tetraacetate, and (2) subsequent Reformatsky reaction of the 23,24-dinor-22-aldehydes with ethyl bromoacetate in the presence of activated Zn as a catalyst with the reaction temperature maintained precisely at 75 °C. The absolute configuration of the chiral center at C-22 of each epimer was established by single-crystal X-ray diffraction data using its ethyl ester-peracetate derivative. The (1)H- and (13)C-NMR spectra that permit the (22R)- and (22S)-epimers to be distinguished are reported as well as the specific (1)H shift effects induced by C(5)D(5)N. Bile acids having hydroxyl groups at C-22 are present in a variety of animal biles, previously have been difficult to identify, and are known to have distinctive physicochemical and biological properties.
authors.affiliation: Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo, 156-8550, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Omura
authors.forename: Ayumi
authors.initials: A
authors.lastname: Ohsaki
authors.forename: Biao
authors.initials: B
authors.lastname: Zhou
authors.forename: Manaka
authors.initials: M
authors.lastname: Kushida
authors.forename: Takashi
authors.initials: T
authors.lastname: Mitsuma
authors.forename: Akiko
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Lee R
authors.initials: LR
authors.lastname: Hagey
authors.forename: Alan F
authors.initials: AF
authors.lastname: Hofmann
authors.forename: Takashi
authors.initials: T
authors.lastname: Iida
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry; D001647:Bile Acids and Salts / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D002635:Chenodeoxycholic Acid / Q000737:chemistry; D019826:Cholic Acid / Q000737:chemistry; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008956:Models, Chemical; D015394:Molecular Structure; D015203:Reproducibility of Results; D015032:Zinc / Q000737:chemistry
chemical_list: D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D019826:Cholic Acid; D015032:Zinc