Synthesis of 3alpha,7alpha,14alpha-trihydroxy-5beta-cholan-24-oic acid: a potential primary bile acid in vertebrates.
A method for the synthesis of 3alpha,7alpha,14alpha-trihydroxy-5beta-cholan-24-oic acid which is a possible candidate of bile acid metabolite in vertebrates was developed. The principal reactions involved were 1). stereoselective remote-hydroxylation of methyl ursodeoxycholate diacetate with dimethyldioxirane, 2). site-selective protection at C-3 by tert-butyldimethylsilylation of the resulting 3alpha,7alpha,14alpha-trihydroxy ester, 3). oxidation of the diol with pyridinium dichromate adsorbed on activated alumina, 4). stereoselective reduction of the 7-ketone with zinc borohydride, and 5). cleavage of the protecting group at C-3 with p-toluenesulfonic acid. A facile elimination of the 14alpha-hydroxy group under an acidic or neutral condition is also described. The synthetic reference compound is now available for comparison with unidentified biliary bile acids detected in vertebrate bile.
Department of Chemistry, College of Humanities and Sciences, Nihon University, Tokyo, Japan.
Genta
G
Kakiyama
Takashi
T
Iida
Takaaki
T
Goto
Nariyasu
N
Mano
Junichi
J
Goto
Toshio
T
Nambara
D000818:Animals; D001647:Bile Acids and Salts / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D002793:Cholic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D014714:Vertebrates / Q000378:metabolism
C490075:3,7,14-trihydroxycholanoic acid; D001647:Bile Acids and Salts; D002793:Cholic Acids