title: Chemical synthesis of the (25R)- and (25S)-epimers of 3α,7α,12α-trihydroxy-5α-cholestan-27-oic acid as well as their corresponding glycine and taurine conjugates.
abstract: The (25R)- and (25S)-epimers of C(27) 3α,7α,12α-trihydroxy-5α-cholestan-27-oic acid as well as their corresponding N-acylamidate conjugates with glycine or taurine were prepared starting from cholic acid in 14 steps. The principal reactions involved were (1) reduction of a key intermediary C(24)allo-cholic acid performate with NaBH(4)/triethylamine/ethyl chloroformate, (2) iodination of the resulting 3,7,12-triformyloxy-5α-cholan-24-ol with I(2)/triphenylphosphine; (3) nucleophilic substitution of the iodo derivative with diethylmethyl malonate/NaH; and (4) hydrolysis of the resulting 3,7,12-triformyloxy-25-methyl-26,27-diethyl ester with KOH, followed by decarboxylation of the geminal dicarboxylic acid with LiCl. N-Acylamidation of the resulting (25R)/(25S)-3α,7α,12α-trihydroxy-5α-cholestan-27-oic acid mixture with glycine or taurine afforded the corresponding epimeric mixtures of the glycine and taurine conjugates. The (25R)- and (25S)-epimers of the three variants of unconjugated and conjugated 3α,7α,12α-trihydroxy-5α-cholestan-27-oic acid were efficiently separated by HPLC on a reversed-phase C(18) column and their structural characteristics, particularly the chiral center at C-25, delineated using (1)H and (13)C NMR. These synthetic compounds should be useful as authentic reference standards for establishing their presence in bile as well as being useful in studies on the biosynthesis of allo-bile acids from cholesterol.
authors.affiliation: Department of Chemistry, College of Humanities & Sciences, Nihon University, Setagaya, Tokyo, Japan.
authors.forename: Shoujiro
authors.initials: S
authors.lastname: Ogawa
authors.forename: Kuniko
authors.initials: K
authors.lastname: Mitamura
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ikegawa
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Krasowski
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: D001647:Bile Acids and Salts / Q000096:biosynthesis / Q000737:chemistry; D002777:Cholestanols / Q000138:chemical synthesis / Q000737:chemistry*; D019826:Cholic Acid / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism
chemical_list: C562007:3,7,12-trihydroxycholestan-27-oic acid; D001647:Bile Acids and Salts; D002777:Cholestanols; D019826:Cholic Acid