The synthesis of taurine-conjugated bile acids and bile acid sulfates labeled with ¹⁴C or ³H in the taurine moiety

Studies of bile acid transport systems require radio-labeled taurine-conjugated bile acids with high specific activity. An established synthetic procedure was optimized to provide mild, fast, and effective conjugation of radio-labeled taurine with different types of bile acids, including those with labile 7α-hydroxy-3-oxo-Δ⁴ or 3β,7α-dihydroxy-Δ⁵ structures. Taurine labeled with ¹⁴C or ³H was reacted with excess bile acid anhydride formed from the tributylamine salt and ethylchloroformate (2/1 M/M) in aqueous dioxane for 15 min at room temperature. The yields were higher than 95% and less than 2% side products were formed. Bile acid sulfates were conjugated with ¹⁴C- or ³H-labeled taurine by using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline as the coupling reagent. The products were effectively purified by chromatography of the sodium salts on Sephadex LH-20. The yields of taurine-conjugated bile acid sulfates were 65-70%.