Synthesis of 1β-hydroxydeoxycholic acid in H-2 and unlabeled forms

Abstract

1β-hydroxydeoxycholic acid in unlabeled and stable isotope labeled forms was required for use as a biomarker for Cytochrome P450 3A4/5 activity. A lengthy synthesis was undertaken to deliver the unlabeled compound and in the process, to develop a route to the deuterium labeled compound. The synthesis of the unlabeled compound was completed but in a very low yield. Concurrent with the synthetic approach, a biosynthetic route was pursued and this approach proved to be much more rapid and afforded the compound in both unlabeled and deuterium labeled forms in a 1-step oxidation from deoxycholic acid and [D₄ ]deoxycholic acid, respectively.

Keywords: Cytochrome P450 3A4; NMR; Steroid; biocatalysis.