Synthesis of ?-Muricholic Acid by One-Pot Enzymatic Mitsunobu Inversion using Hydroxysteroid Dehydrogenases

The biocatalyzed conversion of hyocholic acid (3?,6?,7?-trihydroxy-5?-cholan-24-oic acid) into ?-muricholic acid (3?,6?,7?-trihydroxy-5?-cholan-24-oic acid) has been obtained exploiting a small library of 7?- and 7?-HSDHs (hydroxysteroid dehydrogenases). The process has been optimized and performed avoiding the isolation of the 7-oxo intermediate using the appropriate coupled enzymes for the in situ cofactor regeneration. Moreover, the biocatalyzed reduction of 6,7-dioxolithocholic acid (3?-hydroxy-6,7-dioxo-5?-cholan-24-oic acid) was also investigated.