Stereoselective Reduction of Steroidal 4‑Ene-3-ketones in the Presence of Biomass-Derived Ionic Liquids Leading to Biologically Important 5β-Steroids
The stereoselective reduction of the steroidal 4-ene-3-ketone moiety (enone) affords the 5β-steroid backbone that is a key structural element of biologically important neuroactive steroids. Neurosteroids have been currently studied as novel and potent central nervous system drug-like compounds for t...
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| Published in: | ACS omega Vol. 9; no. 6; pp. 7043 - 7052 |
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| Main Authors: | , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
American Chemical Society
13-02-2024
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| Online Access: | Get full text |
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| Summary: | The stereoselective reduction of the steroidal 4-ene-3-ketone moiety (enone) affords the 5β-steroid backbone that is a key structural element of biologically important neuroactive steroids. Neurosteroids have been currently studied as novel and potent central nervous system drug-like compounds for the treatment of, e.g., postpartum depression. As a green methodology, we studied the palladium-catalyzed hydrogenation of steroidal 4-ene-3-ketones in the presence of ionic liquids derived from natural carboxylic acids. The hydrogenation proceeds with improved 5β-selectivity in the presence of tetrabutylammonium carboxylates as additives compared to the exclusive use of an organic solvent. Under optimal conditions, using tetrabutylammonium d-mandelate, the reduction of testosterone led to 5β-dihydrotestosterone in high yield and stereoselectivity and no byproduct formation was observed. Moreover, the catalyst could be recycled. The presence of additional substituents on the steroid backbone showed a significant effect on the 5β-selectivity. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 2470-1343 2470-1343 |
| DOI: | 10.1021/acsomega.3c08963 |