A new approach to the side chain formation of 24-alkyl-22-hydroxy steroids: Application to the preparation of early brassinolide biosynthetic precursors

A new synthetic route to 22S-hydroxy-24R-methyl steroids has been developed and applied for the preparation of cathasterone, (22S)-hydroxycampesterol, and 6-deoxocathasterone, which are precursors in the early stages of the biosynthesis of brassinolide. The construction of the steroid side chain with the correct stereochemistry at C-24 is based on the use of Claisen rearrangement. The introduction of the 22-hydroxyl group has been achieved by epoxidation of the Δ22-double bond, nucleophilic opening of the intermediate mesyl epoxide with sodium sulfide, and desulfurization of the formed tetrahydrothiophenes with Raney nickel.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A new synthetic route to 22S-hydroxy-24R-methyl steroids has been developed. ► 22-Hydroxy-23,26-thioderivatives were used as key intermediates. ► Cathasterone, 22S-hydroxycampesterol, and 6-deoxocathasterone have been prepared. ► Steroidal 6-methyl ethers are oxidized with methyl(trifluoromethyl)dioxirane to 6-ketones.