%0 Journal Article
%T Hydroxysteroid Dehydrogenase-Catalyzed Highly Regio-, Chemo-, and Enantioselective Hydrogenation of 3-Keto in Steroids.
%A Zeng C
%A Xu S
%A Shen J
%A Zhao S
%A Xu X
%A Peng L
%J Org Lett
%V 26
%N 1
%D 2024 01 12
%M 38127069
%F 6.072
%R 10.1021/acs.orglett.3c03557
%X 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.