Efficient preparative-scale enzymatic synthesis of specifically deuteriated bile acids

Abstract

The regio- and stereo-specific syntheses of [3α-²H]-3β-hydroxy-7,12-dioxo-5β-cholan-24-oic acid, [7β-²H]-7α-hydroxy-3,12-dioxo-5β-cholan-24-oic acid, and [12β-²H]-12α-hydroxy-3,7-dioxo-5β-cholan-24-oic acid have been carried out on preparative scale by coupling the reduction of 3,7,12-trioxo-5β-cholan-24-oic acid, catalyzed by 3β,17β-, 7α-or 12α-hydroxysteroid dehydrogenase, to the oxidation of [1-²H]glucose, catalyzed by glucose dehydrogenase. The transfer of deuterium from glucose to bile acid was mediated by catalytic amounts of coenzyme continuously recycled in situ. The isotopic purity of deuteriated bile acids, determined by ¹H n.m.r. spectrometry, was ≥ 94%.