School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Chem Commun (Camb). 2019 Mar 19;55(24):3544-3547. doi: 10.1039/c8cc09949a.
A unified strategy enabled the enantioselective syntheses of (-)-scholarisine G, (+)-melodinine E, (-)-leuconoxine and (-)-mersicarpine from a common 2-alkylated indole intermediate bearing an all-carbon quaternary stereogenic center. The Smith-modified Madelung indole synthesis was used to couple simple o-toluidine with chiral lactone (+)-8, incorporating the key elements for further cyclizations. Lactone (+)-8 was prepared via a palladium-catalyzed intermolecular asymmetric allylic alkylation. The unified and protecting-group-free reaction sequences allowed the synthesis of these alkaloids in a maximum of 10 steps and with high efficiency.
一种统一的策略使（-）-scholarisine G、（+）-melodinine E、（-）-leuconoxine 和（-）-mersicarpine 能够从带有全碳季立体中心的共同 2-烷基化吲哚中间体进行对映选择性合成。Smith 修饰的 Madelung 吲哚合成用于与手性内酯（+）-8 偶联简单的邻甲苯胺，其中包含进一步环化的关键元素。内酯（+）-8 通过钯催化的分子间不对称烯丙基烷基化反应制备。统一的和无保护基的反应序列允许这些生物碱以最高 10 步和高效率合成。
