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

Area of Science:

• Organic Chemistry
• Biochemistry
• Synthetic Chemistry

Background:

• Bile acids are crucial biological molecules with diverse physiological roles.
• Existing methods for modifying bile acids often yield unstable intermediates.
• Bile acid acetates have been used as synthetic precursors, but with limitations.

Purpose of the Study:

• To develop a novel, high-yield method for preparing performylated bile acids.
• To investigate the stability and synthetic utility of these performylated bile acids.
• To establish performylated bile acids as superior starting materials for targeted bile acid synthesis.

Main Methods:

• A new formylation procedure involving heating bile acids in formic acid with perchloric acid catalyst, followed by acetic anhydride addition.
• Isolation of performylated bile acids by simple dilution with water.
• Partial deformylation using methanolic ammonia, sodium methoxide, or sodium hydroxide.

Main Results:

• Performylated bile acids obtained in quantitative yield.
• Formyl groups demonstrated unexpected stability under various reaction conditions.
• Partial deformylation yielded 3-hydroxy formyl bile acids in high yield.

Conclusions:

• The new formylation procedure provides stable performylated bile acids efficiently.
• Performylated bile acids are more suitable precursors than bile acid acetates for synthetic applications.
• These compounds facilitate the synthesis of C-24 labeled bile acids and specifically modified 3-hydroxy bile acids, such as 3-monosulfates and 3-monoglucuronides.