Partial synthesis of the two 3α:7α:12α-trihydroxycoprostanic acids and of similar bile acids with extended side chains

Abstract

The Kolbe electrolytic cross-coupling synthesis was used to synthesize homocholic, bishomocholic, 3[alpha]:7[alpha]:12[alpha]-tri-hydroxy-25-L-coprostanic and two (25-Land 25-D)-3[alpha]:7[alpha]:12[alpha]-trihydroxyhomocoprostanic acids, the latter 2 compounds being thus related to L- and D-[beta]-methylglutaric acids and hence to L- and D-glyceraldehyde. The two (25-L and 25-D)-3[alpha]:7[alpha]:12[alpha]-trihydroxyhomo-coprostanic acids were degraded by the Wieland-Barbier method into the 2 corresponding (25-L and 25-D)-3[alpha]:7[alpha]:12[alpha]-trihydroxycoprostanic acids. These latter 2 acids were identical with the 2 naturally occurring 3[alpha]:7[alpha]:12[alpha]-trihydroxycoprostan-26-oic acids (Japanese "[alpha]-" and "[beta]-" trihydroxycoprostanic acids respectively), which were isolated from the biles of various species. The formation of a new asymmetric center by the oxidation in vivo of a methyl group in cholesterol to give bile alcohols or bile acids may be considered to be non-specific, in the sense that both optical isomers are obtained.