Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität, München, and Center for Integrated Protein Science, 81377 Munich, Germany.
Nat Chem. 2011 Jun 19;3(7):543-5. doi: 10.1038/nchem.1072.
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 Sharpless 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.
洛林碱（1）是一种小分子生物碱，尽管其结构看似简单，但对合成化学家来说却极具挑战性。它已经存在了一个多世纪，并且已经进行了广泛的生物学研究，但迄今为止仅完成了两个全合成。在这里，我们报告了洛林碱的不对称全合成，该合成步骤不到十步，非常简短。我们的合成包括 Sharpless 环氧化反应、Grubbs 烯烃复分解反应和前所未有的环间氨基溴化反应，将一个八元环氨基甲酸酯转化为溴代吡咯里西啶。该合成具有高度的化学和立体选择性，并可获得洛林碱类生物碱的几个成员。它提供了足够的材料，支持一个旨在研究植物、真菌、昆虫和细菌之间复杂相互作用的项目，这些相互作用是由洛林碱类生物碱介导的。
