Chemical synthesis of 7-oxygenated 12α-hydroxy steroid derivatives to enable the biochemical characterization of cytochrome P450 8B1, the oxysterol 12α-hydroxylase enzyme implicated in cardiovascular health and obesity.

Cholic acid is the endogenous 12α-hydroxylated bile acid, which possesses enhanced cholesterol absorption properties compared to its 12-desoxy counterpart, chenodeoxycholic acid. The oxysterol 12α-hydroxylase enzyme is cytochrome P450 8B1 (P450 8B1), which regioselectively and stereoselectively incorporates the 12α-hydroxy group in 7α-hydroxycholest-4-en-3-one, the biosynthetic precursor of cholic acid. Despite the vital role of P450 8B1 activity in cardiovascular health, research studies of other 12α-hydroxy steroid derivatives are rare.