A novel and easy protocol to obtain 6-alkoxy-Δ4,6-diene-3-one derivatives from available sterols

• Published in: Steroids 2023-12, Vol.200, p.109323-109323, Article 109323
• Main Authors: Martínez-Pascual, Roxana, Felipe-Zaragoza, Lidia Gabriela, Peña-Rico, Miguel Ángel, Cruz-Nolasco, Alain, Pérez-Picaso, Lemuel, Núñez-López, Samuel, López-Torres, Adolfo, Viñas-Bravo, Omar
• Format: Article
• Language: English
• Subjects: 6-alkoxy-Δ4,6-diene-3-one; Keto/enol ether conversion; Molecular iodine; Sterols
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2023.109323

[Display omitted] •Simple methodology to access 6-alkoxy-Δ4,6-diene-3-one derivatives has been achieved.•Molecular iodine as a catalyst for a keto/enol ether transformation was used.•Molecular iodine induced Michel additions in a 16-dehydropregnenolone derivative. Herein we report an unprecedented and efficient methodology for accessing 6-alkoxy-Δ4,6-diene-3-one derivatives. Such scaffolds were serendipitously obtained in the course of the study of the reaction of Δ4-3-keto steroids with catalytic amounts of iodine in refluxing methanol. A series of 6-methoxy and 6-ethoxy- Δ4,6-diene-3-ones were prepared from easily-available sterols in a two-step sequence; first, oxidation of sterols furnished the Δ4-3-keto steroids, which were then refluxed with ethanol or methanol with I2 as catalyst to obtain a series of ten derivatives. Furthermore, this protocol was also effective for the introduction of a larger carbon chain at C-6. Druglikeliness properties of synthesized compounds were predicted using the SwissADME tool.