分子内氧化偶联反应在合成复杂吲哚生物碱骨架中的应用

Intramolecular Oxidative Coupling: Applications in Synthesis of Complex Indole Akaloid Scaffolds

通过含有吲哚底物的分子内氧化偶联反应,成功地构建了Communesin家族生物碱的螺吲哚啉季碳中心,从而完成了(-)-Communesins A,B和F的对映选择性合成.接下来我们发展了分子内氧化偶联/缩合串联反应策略,得到了天然产物(-)-Vincorine的核心四环骨架,然后再经过五步转化完成了Vincorine的全合成.从药物化学角度来看,分子内氧化偶联/缩合串联提供了一个快速方便地合成含有多环吲哚啉骨架的方法.采用相同的串联反应策略,我们分别从色胺衍生的β-酮酸酰胺和丙二酸二酰胺出发,一步构建了多环螺吲哚啉和多环吲哚啉并吡咯环骨架分子.

Intramolecular oxidative coupling of tryptamine incorporated amide was used to create the quaternary spiroin- doline carbon center of communesins, which enabled a short asymmetric synthesis of （--）-communesins A and B and F. The fused tetra-ring framework of Vincorine was established by an intrarnolecular oxidative coupling/condensative cyclization process, which was further advanced to （--）-vincorine in 5 steps. From a medicinal standpoint, such a cascade process pro- vides a highly diverse, efficient method for the construction ofpolycyclic spiroindoline scaffolds. Starting from easily accessi- ble tryptamine incorporated β-ketoamides and malonamides, polyclic spiroindolines and pyrroloindolines could be directly obtained bv adopting the same cascade strategy.