First chemical synthesis, aggregation behavior and cholesterol solubilization properties of pythocholic acid and 16-hydroxycholic acid

Abstract

The first chemical synthesis of pythocholic acid, a major component of python's bile, and 3α,7α,12α,16α-tetrahydroxy-5β-cholan-24-oic acid (16α-hydroxycholic acid), a minor component in Shoebill stork's bile, was achieved starting from readily available cholic acid in overall yields of 5% and 5.5%, respectively, through a common intermediate. A biomimetic template-directed remote functionalization strategy was utilized to selectively functionalize C-16 of the steroid skeleton. This synthesis involves a series of regio and chemoselective transformations. Pythocholic acid showed unusually low critical micellar concentration (CMC) with high cholesterol solubilization ability.