An efficient synthesis of loline alkaloids
An efficient synthesis of loline alkaloids
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DOI：
10.1038/nchem.1072
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发表时间：
2011-07-01
期刊：
影响因子：
21.8
通讯作者：
Trauner, Dirk
中科院分区：
文献类型：
--
作者：
Cakmak, Mesut;Mayer, Peter;Trauner, Dirk
Loline (1) 是一种小生物碱，尽管其结构看起来很简单，但却给合成化学家带来了令人惊讶的挑战。它已为人所知一个多世纪了，并且一直是广泛的生物学研究的主题，但迄今为止仅实现了两种全合成。在这里，我们报告了黑麦草碱的不对称全合成，其步骤少于十个，非常短。我们的合成结合了夏普少环氧化、格拉布斯烯烃复分解和前所未有的跨环氨基溴化，将八元环氨基甲酸酯转化为溴吡咯里西啶。该合成具有高度的化学选择性和立体选择性，并且可以得到黑麦草碱生物碱家族的多个成员。它提供了足够的材料来支持旨在研究由黑麦草碱生物碱调节的植物、真菌、昆虫和细菌之间复杂相互作用的计划。
Loline (1) is a small alkaloid that, in spite of its simple-looking structure, has posed surprising challenges to synthetic chemists. It has been known for more than a century and has been the subject of extensive biological investigations, but only two total syntheses have been achieved to date. Here, we report an asymmetric total synthesis of loline that, with less then ten steps, is remarkably short. Our synthesis incorporates a Sharp less epoxidation, a Grubbs olefin metathesis and an unprecedented transannular aminobromination, which converts an eight-membered cyclic carbamate into a bromopyrrolizidine. The synthesis is marked by a high degree of chemo- and stereoselectivity and gives access to several members of the loline alkaloid family. It delivers sufficient material to support a programme aimed at studying the complex interactions between plants, fungi, insects and bacteria brokered by loline alkaloids.