“含芳基取代全碳季碳的氢化吲哚”单元不对称构建及在石蒜科生物碱合成中的应用

The alkaloids having a hydroindole nucleus with arylsubstiuted all-carbon quaternary stereocenter have attracted considerable interest in the chemistry community due to broad range of biological activities. However, less enantioselective strategy has been explored in the installation of functionalized hydroindole. Encompassing the asymmetric synthesis of hydroindole nucleus, unprecedented enantioselective catalytic intramolecular hydroamination and intramolecular aminooxygenation of prochiral cyclohexa-2,5-dienes could be designed on the basis of enantioselective desymmetrization, this would provid a new method for the expeditious assembly of hydroindole nucleus bearing the crucial arylsubstiuted all-carbon quaternary stereocenter. On the basis of this key asymmetric methodology, the chiral total synthesis of two Amaryllidaceae alkaloids, (–)-Amabiline and (–)-Augustamine, will be explored. The studies would not only chemically enrich the construction of a chiral all-carbon quaternary stereocenter embedded in the useful functionalized hydroindole nucleus but also illustrate a potential of asymmetric catalysis based on cyclohexadienes chemistry in the asymmetric synthesis of related nature products.

“含芳基取代全碳季碳的氢化吲哚”单元的天然生物碱具有很好的生物活性，一直受到有机合成化学家的青睐，而该结构单元的有机催化条件下的不对称构建研究还非常有限。鉴于此，本项目拟以“含芳基取代全碳季碳的氢化吲哚”单元的不对称构建为研究目标，利用对映选择性去对称化概念，设计新颖的 “不对称催化的 2, 5-环己二烯胺分子内氢胺化反应与胺氧化反应”，策略性地实现该类氢化吲哚单元与芳基取代全碳季碳的一步不对称催化构建，并以此为关键反应，简捷地、高效地、多样性地实现石蒜科生物碱 (–)-Amabiline 与 (–)-Augustamine 的不对称全合成。该项目研究不仅能为“芳基取代全碳季碳氢化吲哚”单元的不对称催化构筑提供新方法，而且拓展了不对称催化的环己双烯去对称化研究在天然产物全合成中的应用。

我们课题组一直关注基于邻亚甲基苯醌参与的串联环化反应，利用高亲电性的邻亚甲基苯醌合成砌块，该项目主要开展了一下四个方面的工作。1）次级膦氧与原位生成的邻亚甲基苯进行的phospha-Michael 加成环化反应研究； 2）Lewis 酸催化的邻亚甲基苯醌与富电子苯酚进行的串联1，4-加成环化反应研究；3）Lewis 碱催化的邻亚甲基苯醌与MBH 碳酸脂进行的[4+3]串联环化反应研究；4）Lewis 酸催化的邻亚甲基苯醌与芳基腙进行的[串联环化反应研究。这些方法发展不仅仅有效补充了这些有机合成骨架的合成方法，而且为将来邻亚甲基苯醌化学的反应设计提供思路。