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Published on: September 21, 2011
From alpha to beta: a two-step strategy for stereoinversion of C16 glucocorticoids
Jianhai Wei1,2, Yajiao Zhang1,2, Yuan Tao1,2
1Engineering Center of Catalysis and Synthesis for Chiral Molecules, Fudan University, 200433 Shanghai, China. rfchen@fudan.edu.cn.
None:
C16-Methylcorticoids are important anti-inflammatory agents whose activity depends on the C16 methyl configuration. However, access to C16β analogues remains challenging. Herein, we report the first concise two-step stereoinversion of C16α-methylcorticoids to C16β diastereomers through C17 hydroxyl elimination followed by Mn-catalyzed Mukaiyama hydration. Betamethasone, beclomethasone, clobetasol, clobetamethasone, and difluorolaxone were obtained in useful yields with high diastereoselectivities (19 : 1 to >99 : 1 dr).
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