Hydroxysteroid Dehydrogenase-Catalyzed Highly Regio‑, Chemo‑, and Enantioselective Hydrogenation of 3‑Keto in Steroids

A highly
selective hydrogenation of 3-keto in steroids to 3-hydroxyl
steroids catalyzed by hydroxysteroid dehydrogenases (HSDHs) was demonstrated.
The Ct3α-HSDH-catalyzed hydrogenation generated 3α-hydroxyl
steroids as the main enantiopure isomers in high yields, while the
Ss3β-HSDH catalytic system afforded 3β-hydroxyl steroids
in excellent yields. In both catalytic systems, the hydrogenation
proceeded regioselectively at 3-keto with 7-, 11-, 17-, and 20-keto
almost unreacted, and chemoselectively with the CC bond and
ester group unattacked. Our HSDH-promoted hydrogenation showed advantages
like high regio-, chemo-, and enantioselectivity, good yields, mild
conditions, a wide substrate scope, and being suitable for gram-scale
synthesis. Notably, bioactive molecules like dehydroepiandrosterone,
brienolone, and alfaxalone were obtained facilely in high yields via
our hydrogenation approach.