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

Abstract

Herein we report an unprecedented and efficient methodology for accessing 6-alkoxy-Δ^4,6-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- Δ^4,6-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.

Keywords: 6-alkoxy-Δ(4,6)-diene-3-one; Keto/enol ether conversion; Molecular iodine; Sterols.