Formylated bile acids: Improved synthesis, properties, and partial deformylation

Abstract

Pure performylated bile acids are obtained in quantitative yield by anew formylation procedure. The procedure involves heating the bile acids in 90% formic acid containing catalytic amount of perchloric acid and then adding acetic anhydride slowly until effervescence occurs. Pure performylated bile acids are then isolated simply by diluting the reaction mixture with water. Contrary to what was believed by past investigations, the formyl groups on these compounds are quite stable to various reaction conditions. The stability and ready availability of these compounds make them more suitable candidates than their counterpart—bile acid acetates for use as starting material in various synthetic schemes, such as C-24 labeled bile acids, etc. The partial deformylation of these formates can be effected by using methanolic ammonia, sodium methoxide in methanol, or sodium hydroxide in aqueous acetone. The resulting 3-hydroxy formyl bile acids are obtained in high yield and are the best starting materials for the synthesis of bile acids with specific modification at 3-hydroxyl group, such as the synthesis of bile acid 3-monosulfates and 3-monoglucuronides.