Enantioselective catalytic approach to the C23–C28 subunit of 24α-methyl steroids

• Published in: Steroids 2019-08, Vol.148, p.82-90
• Main Authors: Yakimchyk, Viktoryia S., Kazlova, Volha V., Hurski, Alaksiej L., Savchenko, Rimma G., Kostyleva, Svetlana A., Zhabinskii, Vladimir N., Khripach, Vladimir A.
• Format: Article
• Language: English
• Subjects: Campesterol; Catalysis; cis-22-Dehydrocampesterol; Decarbonylation; Michael addition; Molecular Conformation; Ni-catalyzed decarboxylation; Pyrrolidines - chemistry; Stereoisomerism; Steroids - chemical synthesis; Steroids - chemistry
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2019.05.003

[Display omitted] •A new catalytic way to C23–C28 fragment of campestanes is reported.•Two ways of reductive denitromethylation have been developed.•The subunit can be attached to a steroid by the Julia-Kocienski olefination. Enantioselective synthesis of C23–C28 subunit of campestane steroids based on catalytic methods is reported. The synthesis was started from (S)-2-isopropyl-4-nitrobutan-1-ol, which is easily accessible by the reaction between isovaleraldehyde and nitroethylene catalyzed by only 2% of (S)-trimethylsilyldiphenylprolinol. Removal of one “extra” carbon from the nitroalcohol was achieved by Ni-catalyzed hydrodecarboxylation of the redox-active ester intermediate. The synthesized C23–C28 fragment was attached to a steroidal core by Julia-Kocienski reaction of a steroidal aldehyde with metallated C23–C28 sulfone. The obtained product of olefination was easily transformed to a precursor of campesterol and (Z)-22-dehydrocampesterol.