Enantioselective Total Synthesis of Cannogenol-3-O-α-L-rhamnoside via Sequential Cu(II)-Catalyzed Michael Addition/Intramolecular Aldol Cyclization Reactions
Enantioselective Total Synthesis of Cannogenol-3-O-α-L-rhamnoside via Sequential Cu(II)-Catalyzed Michael Addition/Intramolecular Aldol Cyclization Reactions
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DOI：
10.1021/acs.orglett.7b03513
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发表时间：
2018-01-05
期刊：
影响因子：
5.2
通讯作者：
Nagorny, Pavel
中科院分区：
文献类型：
--
作者：
Bhattarai, Bijay;Nagorny, Pavel
通过 18 个线性步骤，实现了天然卡烯内酯 cannogenol 和 cannogenol-3-O-α-L-rhamnoside 的简洁且可扩展的对映选择性全合成。该合成采用 Cu(II) 催化的对映选择性和非对映选择性 Michael 反应/串联羟醛环化和一锅还原/转座，从而快速（6 个线性步骤）组装含有 C19 氧化的功能化中间体，该中间体可以精制为 Cardenolide cannogenol。此外，还开发了一种在合成cannogenol的C3位实现区域和立体选择性糖基化的策略，并将其应用于cannogenol-3-O-α-L-鼠李糖苷的制备。
A concise and scalable enantioselective total synthesis of the natural cardenolides cannogenol and cannogenol-3-O-alpha-L-rhamnoside has been achieved in 18 linear steps. The synthesis features a Cu(II)-catalyzed enantioselective and diastereoselective Michael reaction/tandem aldol cyclization and a one-pot reduction/transposition, which resulted in a rapid (6 linear steps) assembly of a functionalized intermediate containing C19 oxygenation that could be elaborated to cardenolide cannogenol. In addition, a strategy for achieving regio- and stereoselective glycosylation at the C3 position of synthetic cannogenol was developed and applied to the preparation of cannogenol-3-O-alpha-L-rhamnoside.