Short and efficient syntheses of protoberberine alkaloids using palladium-catalyzed enolate arylation.
Short and efficient syntheses of protoberberine alkaloids using palladium-catalyzed enolate arylation.
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DOI：
10.1002/anie.201409164
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发表时间：
2014-12-22
期刊：
影响因子：
--
通讯作者：
Donohoe TJ
中科院分区：
文献类型：
--
作者：
Gatland AE;Pilgrim BS;Procopiou PA;Donohoe TJ
本文报道了一种具有生物活性的生物碱小檗碱的合成方法，并利用钯催化的烯酸芳化反应形成异喹啉核心。总收率为50%，比以前的单一合成有了很大的提高。通过设计，这种模块化的路线允许通过取代现成的芳基溴和酮偶联伙伴快速合成原小檗碱家族的其他成员（例如，假黄花碱和棕榈碱）。此外，通过将烯醇酸芳基化与原位功能化相结合，取代基可以快速和区域选择性地引入到生物碱C13位置，如脱氢根碱的全合成所证明的那样。通过避免亲电芳取代反应来制造异喹啉，可以直接获得具有更多不同电子性质的类似物，例如这里合成的含氟衍生物。
A concise synthesis of the biologically active alkaloid berberine is reported, and a versatile palladium-catalyzed enolate arylation is used to form the isoquinoline core. The overall yield of 50 % is a large improvement over the single, previous synthesis. By design, this modular route allows the rapid synthesis of other members of the protoberberine family (e.g., pseudocoptisine and palmatine) by substitution of the readily available aryl bromide and ketone coupling partners. Moreover, by combining enolate arylation with in situ functionalization, substituents can be rapidly and regioselectively introduced at the alkaloid C13 position, as demonstrated by the total synthesis of dehydrocorydaline. The avoidance of electrophilic aromatic substitution reactions to make the isoquinoline allows direct access to analogues possessing more varied electronic properties, such as the fluorine-containing derivative synthesized here.