对映选择性全合成双喹啉生物碱：一种模块化的“从内到外”方法。
The Enantioselective Total Synthesis of Bisquinolizidine Alkaloids: A Modular "Inside-Out" Approach.
机构信息
Organic Chemistry Laboratory, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.
Inorganic Chemistry Laboratory, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.
出版信息
Angew Chem Int Ed Engl. 2018 Feb 23;57(9):2432-2435. doi: 10.1002/anie.201712852. Epub 2018 Feb 12.
Bisquinolizidine alkaloids are characterized by a chiral bispidine core (3,7-diazabicyclo[3.3.1]nonane) to which combinations of an α,N-fused 2-pyridone, an endo- or exo-α,N-annulated piperidin(on)e, and an exo-allyl substituent are attached. We developed a modular "inside-out" approach that permits access to most members of this class. Its applicability was proven in the asymmetric synthesis of 21 natural bisquinolizidine alkaloids, among them more than ten first enantioselective total syntheses. Key steps are the first successful preparation of both enantiomers of C -symmetric 2,6-dioxobispidine by desymmetrization of a 2,4,6,8-tetraoxo precursor, the construction of the α,N-fused 2-pyridone by using an enamine-bromoacrylic acid strategy, and the installation of endo- or, optionally, exo-annulated piperidin(on)es.
双稠哌啶生物碱的结构特征为一个手性双并吡咯烷核（3,7-二氮杂双环[3.3.1]壬烷），其上连接有各种组合的 α,N-稠合 2-吡啶酮、内或外 α,N-稠合哌啶（吗啉）以及外部烯丙基取代基。我们开发了一种模块化的“从内到外”方法，可用于获得此类化合物的大多数成员。该方法在 21 种天然双稠哌啶生物碱的不对称合成中的适用性得到了证明，其中包括十个以上的首次对映选择性全合成。关键步骤包括通过不对称拆分 2,4,6,8-四氧代前体首次成功制备 C-对称的 2,6-二氧代双并吡咯烷的两种对映异构体，使用烯胺-溴代丙烯酸策略构建 α,N-稠合 2-吡啶酮，以及引入内或外，可选地，稠合的哌啶（吗啉）。
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