title: The regio- and stereo-selective reduction of steroidal 4-en-3-ones using Na₂S₂O₄/NaHCO₃ and CuCl/NaBH₄.
abstract: This paper describes the regio- and stereoselective reduction of △⁴-3-keto moiety in certain steroids using Na₂S₂O₄/NaHCO₃ and CuCl/NaBH₄, respectively. Using either one of the two reduction agents in the reaction, the 17-substituents in the D ring were observed to have clearly influenced the stereoselective reduction of 4-ene in the A ring by the so-called conformational transmission effect. Na₂S₂O₄/NaHCO₃ regioselectively reduced CC at 4-position of 17-substituted-androst-4-en-3-one derivatives to 5α-H-3-one as the main isomer. And as an extended application, Epiandrosterone (11) was further synthesized from androst-4-en-3,17-dione (AD) via four steps. The total yield from this was about 45%. In the presence of CuCl/NaBH₄, △⁴-3-keto conjugated reduction of 17-spirocyclic ethylene ketal protected androst-4-en-3-one derivatives mainly produced 3α-hydroxy-5β-H isomers, at a yield around 81%. Considering the scaffold configuration of 3α-hydroxy-5β-H moiety coincided with that of bile acid analogs, this selective reduction could also be used as an alternative method for the synthetic study of bile acids using AD and its derivatives, which are from the microorganism degradation of natural sterols, as the potential materials. Meanwhile, configurations of the reductive compounds 5b, 6b, 9, 10 and 17e were identified by X-ray diffraction.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Wang
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chen
authors.forename: Yaoqing
authors.initials: Y
authors.lastname: Huang
authors.forename: Jesse
authors.initials: J
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000735:Androstenedione / Q000737:chemistry*; D000738:Androsterone / Q000138:chemical synthesis*; D001647:Bile Acids and Salts / Q000138:chemical synthesis*; D001894:Borohydrides / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D018360:Crystallography, X-Ray; D004227:Dithionite / Q000737:chemistry; D017693:Sodium Bicarbonate / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D001647:Bile Acids and Salts; D001894:Borohydrides; D004227:Dithionite; D000735:Androstenedione; D003300:Copper; C025364:sodium borohydride; D017693:Sodium Bicarbonate; D000738:Androsterone; C028419:cuprous chloride
keywords: 4-En-3-one; Conjugated reduction; Cuprous chloride; Sodium dithionite