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

The biocatalyzed conversion of hyocholic acid (3 alpha,6 alpha,7 alpha-trihydroxy-5 beta-cholan-24-oic acid) into omega-muricholic acid (3 alpha,6 alpha,7 beta-trihydroxy-5 beta-cholan-24-oic acid) has been obtained exploiting a small library of 7 alpha- and 7 beta-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 alpha-hydroxy-6,7-dioxo-5 beta-cholan-24-oic acid) was also investigated.