Quinolizidine-Based Alkaloids: A General Catalytic, Highly Enantio- and Diastereoselective Synthetic Approach
Quinolizidine-Based Alkaloids: A General Catalytic, Highly Enantio- and Diastereoselective Synthetic Approach
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DOI：
10.1055/s-0035-1561289
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发表时间：
2016-01
期刊：
影响因子：
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通讯作者：
Chris Lindemann;C. Schneider
中科院分区：
文献类型：
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作者：
Chris Lindemann;C. Schneider
摘要以一种简单、灵活、立体选择性的方法合成了11个喹嗪类生物碱。作为以多克规模运行的关键步骤，使用有机催化的、高度对映体和非对映体选择性的乙烯基化合物Mukaiyama-Mannich反应，提供已经携带两个立体中心的高度官能化的产物。喹嗪酮核随后通过两个酯基与胺部分的环化反应组装。而桥头碳原子和相邻手性中心的绝对构型是在最初的乙烯基曼尼希反应中建立的，在4-位的立体中心是在最后一步中通过酰胺活化和有机金属加成引入的，利用底物的立体化学控制。利用这一统一的策略，简单以及更复杂的生物碱，在良好的总产率和高立体选择性。其中一些QBA是首次合成，本研究有助于确定它们的绝对构型和相对构型。
Abstract Eleven quinolizidine-based alkaloids (QBAs) were synthesized in a straightforward, flexible, and stereoselective manner. As the key step, which was run on a multi-gram scale, the organocatalytic, highly enantio- and diastereoselective vinylogous Mukaiyama–Mannich reaction was used furnishing highly functionalized products carrying already two stereogenic centers. The quinolizidinone core was subsequently assembled through cyclization reactions of both ester groups with the amine moiety. Whereas the absolute configuration of the bridgehead carbon atom and the adjacent chiral center were established in the initial vinylogous Mannich reaction, the stereogenic center at the 4-position was introduced in the last step through amide activation and organometallic addition exploiting stereochemical control from the substrate. Taking advantage of this unified strategy, simple as well as more complex alkaloids were accessible in good overall yields and with high stereoselectivity. Some of the QBAs were synthesized for the first time and this study could help to assign their absolute and relative configurations.