Synthesis of Steroidal Thioethers via [HDBU][OAc]‐Mediated Michael Addition of Thiols to 16‐Dehydropregnenolone

• Published in: ChemistrySelect (Weinheim) Vol. 7; no. 29
• Main Authors: Maksó, Lilla, Kovács, Krisztina, Andreidesz, Kitti, Gömöry, Ágnes, Mahó, Sándor, Skoda‐Földes, Rita
• Format: Journal Article
• Language: English
• Published: 05.08.2022
• Subjects: antitumor agents; catalysis; catalyst recycling; green chemistry; ionic liquids
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202200967

In the catalytic addition of thiols to 16‐dehydropregnenolone fourteen thioethers were prepared via thiol‐Michael addition reaction in the presence of different aliphatic and aromatic thiols as reagents. [HDBU][OAc] was proved to be an efficient catalyst and solvent providing thioether derivatives in good to excellent yields. The ionic liquid could be reused for five times without noticeable loss of activity. The structures of compounds were confirmed by 1H‐, 13C NMR and IR spectroscopy and mass spectral analysis. A series of these pregnenolone derivatives were evaluated for their cytotoxic activity on breast cancer (MDA‐MB‐231, MCF7) cell lines. [HDBU][OAc] was found to be an efficient catalyst and solvent in thiol‐Michael reactions of steroidal substrates and both aliphatic and aromatic thiols. It ensures a facile separation of products, it is stable under the reaction conditions and recyclable without loss of activity. Biological tests of some products showed a greater decrease in the viability of less curable MDA‐MB‐231 cells.