Site-selective and Metal-free Aliphatic C-H Oxidation Enabled Synthesis of [5,24,25-D3]-(25S)-Δ7-Dafachronic acid

Liu, W.; Li, X.; Chen, J.; Li, T.; Dong, M.; Lei, X.*
Chem. Eur. J. 2015, 21, 5345-5349

Abstract: Steroid hormones play significant roles in both worms and mammalians. (25S)-Δ7-Dafachronic acid (Δ7-DA, 1) is a member of dafachronic acid hormonal series which regulates both development and lifespan of C. elegans. Despite its importance, effective tools for the illumination of its mode of action are lacking. Herein, we report an efficient synthesis of trideuterated […]

Abstract: Steroid hormones play significant roles in both worms and mammalians. (25S)-Δ7-Dafachronic acid (Δ7-DA, 1) is a member of dafachronic acid hormonal series which regulates both development and lifespan of C. elegans. Despite its importance, effective tools for the illumination of its mode of action are lacking. Herein, we report an efficient synthesis of trideuterated Δ7-DA, [5,24,25-D3]-(25S)-Δ7-dafachronic acid (Δ7-DA-d3, 2), as a useful chemical tool for subsequent biological studies. Key steps for this bioinspired synthesis approach include site-selective aliphatic C-H oxidation mediated by methyl(trifluoromethyl)-dioxirane (TFDO), and the iridium/phosphine-oxazoline catalysed late-stage asymmetric deuterium reduction.