Synthesis of sulfate esters of lithocholic acid, glycolithocholic acid, and taurolithocholic acid with sulfur trioxide-triethylamine

Abstract

The facile synthesis of lithocholic acids sulfates by a procedure that produced the desired products in over 90% yield is described. Lithocholic acid sulfate and glycolithocholic acid sulfate were synthesized by reacting lithocholic acid or glycolithocholic acid with sulfur trioxide-triethylamine complex in dimethylformamide for 0.5-1 hr. Taurolithocholic acid sulfate was obtained by conjugating lithocholic acid sulfate with taurine in dimethylformamide at 90 degrees C for 0.5 hr. The one-pot synthesis of taurolithocholic acid sulfate starting from lithocholic acid is also described. This procedure, which generated lithocholic acid sulfate in situ, produced taurolithocholic acid sulfate in 98% yield, compared to an overall yield of less than 10% obtained by previously published procedures.