Synthesis of 24-nor-5 beta-cholan-23-oic acid derivatives: a convenient and efficient one-carbon degradation of the side chain of natural bile acids.
An efficient procedure for obtaining nor-bile acids from natural (C24) bile acids is described. Treatment of formylated bile acids with sodium nitrite in a mixture of trifluoroacetic anhydride with trifluoroacetic acid gives, through a "second order" Beckmann rearrangement, 24-nor-23-nitriles. These compounds, on alkaline hydrolysis, afford the corresponding nor-bile acids in high yields. The sequence was successfully applied to the synthesis of 3 alpha-hydroxy-24-nor-5 beta-cholan-23-oic (norlithocholic) acid, 3 alpha,6 alpha- (norhyodeoxycholic), 3 alpha,7 alpha- (norchenodeoxycholic), 3 alpha,7 beta- (norursodeoxycholic), and 3 alpha,12 alpha-dihydroxy-24-nor-5 beta-cholan-23-oic (nordeoxycholic) acids, as well as 3 alpha,7 alpha,12 alpha-trihydroxy-24-nor-5 beta-cholan-23-oic (norcholic) acid. 13C-NMR spectra of their methyl esters are reported. The procedure provides a more rapid alternative to the Barbier-Wieland degradation for shortening by one methylene group the side chain of natural (C24) bile acids.
Schteingart
C D
CD
Department of Medicine, University of California, San Diego, La Jolla 92093.
Hofmann
A F
AF
D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis; D002793:Cholic Acids / Q000138:chemical synthesis*; D003840:Deoxycholic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis; D006868:Hydrolysis; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation
C051380:23-norchenodeoxycholic acid; D001647:Bile Acids and Salts; D002793:Cholic Acids; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; C033582:23-nordeoxycholic acid; C036933:norcholic acid