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 (&) biIe 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 alka- line hydrolysis, afford the corresponding nor-bile acids in high yields. The sequence was successfully applied to the synthesis of 3a-hydmy-24-nor-5fl-chotan-23-oic (norlithocholic) acid, 3a,6a- (norhyodeoxycholic), 3a,7a- (norchenodeoxycholic), 31470- (nor- unodeoxycholic), and 3a,12a-diiydroxy-24-nor-5~-cholan-23-oic (nordeoxycholic) acids, as well as 3a,7a,l2a-trihydroxy-24-nor-5j3- cho~an-23-oic (norcholic) acid. "C-NMR spectra of their methyl estera are reported. The procedure provides a more rapid alter- native to the Barbier-Wieland degradation for shortening by one methylene group the side chain of natural (Cf4) bile acids.- schteingsrt, C. D., and A. F. Hofmann. Synthesis of 24-nor-58- cholan-23-ok acid derivatives: a convenient and efficient one- carbon degradation of the side chain of natural bile acids.J Lipid Res. 1988. 29 1387-l395.