title: Site-selective and metal-free aliphatic C-H oxidation enabled synthesis of [5,24,25-D3]-(25S)-Δ(7)-dafachronic acid.
abstract: Steroid hormones play significant roles in both worms and mammalians. (25S)-Δ(7)-Dafachronic acid (Δ(7)-DA, 1) is a member of the dafachronic acid hormonal series that 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 Δ(7)-DA, [5,24,25-D3]-(25S)-Δ(7)-dafachronic acid ([D3]-Δ(7)-DA, 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-catalyzed late-stage asymmetric deuterium reduction.
authors.affiliation: Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730 (China), Fax: (+86) 10-80704785 http://www.chem.pku.edu.cn/leigroup/; National Institute of Biological Sciences (NIBS), Changping District, Beijing 102206 (China).
authors.forename: Weilong
authors.initials: W
authors.lastname: Liu
authors.forename: Xiangke
authors.initials: X
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Tiemei
authors.initials: T
authors.lastname: Li
authors.forename: Mengqiu
authors.initials: M
authors.lastname: Dong
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Lei
mesh_terms: D000818:Animals; D002384:Catalysis; D002782:Cholestenes / Q000138:chemical synthesis* / Q000737:chemistry; D003903:Deuterium / Q000138:chemical synthesis / Q000737:chemistry; D005027:Ethylene Oxide / Q000031:analogs & derivatives / Q000737:chemistry; D007495:Iridium / Q000737:chemistry; D010084:Oxidation-Reduction; D010720:Phosphines / Q000737:chemistry
chemical_list: D002782:Cholestenes; D010720:Phosphines; C533800:dafachronic acid; D007495:Iridium; C445840:methyl(trifluoromethyl)dioxirane; D003903:Deuterium; C044646:phosphine; D005027:Ethylene Oxide
keywords: CH oxidation; asymmetric hydrogenation; bioinspired synthesis; deuterium labeling; steroid hormone