Potential bile acid metabolites. 25. Synthesis and chemical properties of stereoisomeric 3alpha,7alpha,16- and 3alpha,7alpha,15-trihydroxy-5beta-cholan-24-oic acids.
Epimeric 3alpha,7alpha,16- and 3alpha,7alpha,15-trihydroxy-5beta-cholan-24-oic acids and some related compounds were synthesized from chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), respectively. The key reaction involved one-step remote oxyfunctionalization of unactivated methine carbons at C-17 of CDCA and at C-14 of UDCA as their methyl ester-peracetate derivatives with dimethyldioxirane (DMDO). After dehydration of the resulting 17alpha- and 14alpha-hydroxy derivatives with POCl(3) or conc. H(2)SO(4), the respective Delta(16)- and Delta(14)-unsaturated products were subjected to hydration via hydroboration followed by oxidation to yield the 3,7,16- and 3,7,15-triketones, respectively. Stereoselective reduction of the respective triketones with tert-butylamine-borane complex afforded the epimeric 3alpha,7alpha,16- or 3alpha,7alpha,15-trihydroxy derivatives exclusively. A facile formation of the corresponding epsilon-lactones between the side chain carboxyl group at C-24 and the 16alpha- (or 16beta-) hydroxyl group in bile acids is also clarified.
Iida
Takashi
T
College of Humanities and Sciences, Nihon University, Japan. takaiida@chs.nihon-u.ac.jp
Hikosaka
Masahiro
M
Kakiyama
Genta
G
Shiraishi
Keisuke
K
Schteingart
Claudio D
CD
Hagey
Lee R
LR
Ton-Nu
Huong-Thu
HT
Hofmann
Alan F
AF
Mano
Nariyasu
N
Goto
Junichi
J
Nambara
Toshio
T
D001647:Bile Acids and Salts / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism
D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid