Synthesis of coenzyme A esters of 3alpha,7alpha,12alpha-trihydroxy- and 3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oic acids for the study of beta-oxidation in bile acid biosynthesis.
3alpha,7alpha,12alpha-Trihydroxy- and 3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oyl CoAs were chemically synthesized by the conventional method for the study of side chain cleavage in bile acid biosynthesis. 3alpha,7alpha,12alpha-Triformyloxy- and 3alpha,7alpha-diformyloxy-5beta-cholan-24-als were initially subjected to the Reformatsky reaction with methyl alpha-bromopropionate, and the products were then converted into methyl 3alpha,7alpha,12alpha-triformyloxy- and 3alpha,7alpha-diformyloxy-24-oxo-5beta-cholestan-26-oates. Protection by acetalization of the 24-oxo-group of these methyl esters with ethylene glycol, followed by alkaline hydrolysis, gave 3alpha,7alpha,12alpha-trihydroxy- and 3alpha,7alpha-dihydroxy-24,24-ethylenedioxy-5beta-cholestan-26-oic acids. These acids were condensed with coenzyme A by a mixed anhydride method, and the resulting CoA esters were treated with 4M-hydrocholic acid to remove the protecting group to give 24-oxo-5beta-cholestanoic acid CoA esters. The chromatographic behaviors of these CoA esters were also investigated.
Kurosawa
T
T
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, 061-0293, Hokkaido, Japan. kurohsuh@hucc.hokudai.ac.jp
Fujiwara
M
M
Nakano
H
H
Sato
M
M
Yoshimura
T
T
Murai
T
T
D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002776:Cholestanes / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003065:Coenzyme A / Q000378:metabolism*; D004952:Esters; D010084:Oxidation-Reduction; D013057:Spectrum Analysis
D001647:Bile Acids and Salts; D002776:Cholestanes; D004952:Esters; D003065:Coenzyme A