对映选择性全合成 (+)-Stephadiamine。
Enantioselective Total Synthesis of (+)-Stephadiamine.
机构信息
Laboratory of Synthesis and Natural Products (LSPN), Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN, BCH5304, CH-1015 Lausanne, Switzerland.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China.
出版信息
J Am Chem Soc. 2023 Mar 8;145(9):5001-5006. doi: 10.1021/jacs.3c00884. Epub 2023 Feb 27.
An asymmetric synthesis of (+)-stephadiamine has been accomplished featuring (a) an enantioselective dearomatizative Michael addition to generate a quaternary stereocenter; (b) a domino sequence involving reductive generation of nitrone from γ-nitro ketone followed by a highly regio- and diastereo-selective intramolecular [3 + 2] cycloaddition to construct the aza[4,3,3]propellane core with concurrent generation of two quaternary stereocenters and two functional groups ready for subsequent transformations; (c) the Curtius rearrangement of the sensitive α,α-disubstituted malonic acid mono ester for the installation of α,α-disubstituted amino ester moiety; (d) a benzylic C-H oxidation under photoredox catalytic conditions; and (e) a highly diastereoselective ketone reduction affording δ-hydroxyester preorganized for lactonization.
（+）-Stephadiamine 的不对称合成已经完成，其特征在于：(a) 通过对映选择性非芳香族 Michael 加成生成季立体中心；(b) 涉及γ-硝基酮还原生成硝酮，然后高度区域和立体选择性的分子内[3 + 2]环加成，构建具有两个季立体中心和两个功能基团的氮杂[4,3,3]螺桨核心，同时生成两个季立体中心和两个功能基团，为后续转化做好准备；(c) 敏感的α,α-二取代丙二酸单酯的Curtius 重排，用于安装α,α-二取代氨基酯部分；(d) 在光氧化还原催化条件下进行苄位 C-H 氧化；(e) 高度非对映选择性酮还原，得到δ-羟基酯，为内酯化做好预组织。
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