BioCIS, Université Paris-Sud, Université Paris-Saclay, CNRS, 92290 Châtenay-Malabry, France.
Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), Université Paris-Sud, Université Paris-Saclay, CNRS, UMR 8182, 91405 Orsay Cedex, France.
Nat Chem. 2017 Feb 27;9(8):793-798. doi: 10.1038/nchem.2735.
Bipleiophylline is a highly complex monoterpene indole alkaloid composed of two pleiocarpamine units anchored on an aromatic spacer platform. The synthesis of bipleiophylline is considered as a mountain to climb by the organic chemistry community. Here, a unified oxidative coupling protocol between indole derivatives and 2,3-dihydroxybenzoic acid, mediated by silver oxide, has been developed to produce the core of bipleiophylline. This method also allows the independent preparation of benzofuro[2,3-b]indolenine and isochromano[3,4-b]indolenine scaffolds, depending only on the nature of the aromatic platform used. The procedure has been applied to simple indole derivatives and to more challenging monoterpene indole alkaloids, thereby furnishing natural-product-like structures. The use of scarce pleiocarpamine as the starting indole allows the first syntheses of bipleiophylline and of its biosynthetic precursor, voacalgine A. The structure of the latter has been reassigned in the course of our investigations by 2D NMR and displays an isochromano[3,4-b]indolenine motif instead of a benzofuro[2,3-b]indolenine.
比莱啡碱是一种高度复杂的单萜吲哚生物碱，由两个 pleiocarpamine 单元锚定在芳香间隔平台上组成。比莱啡碱的合成被有机化学界视为一座难以攀登的山峰。在这里，我们开发了一种统一的氧化偶联协议，通过氧化银介导，使吲哚衍生物和 2,3-二羟基苯甲酸之间发生反应，从而产生比莱啡碱的核心结构。该方法还可以独立制备苯并呋喃[2,3-b]吲哚啉和异吲哚并[3,4-b]吲哚啉支架，这仅取决于所使用的芳香平台的性质。该方法已应用于简单的吲哚衍生物和更具挑战性的单萜吲哚生物碱，从而提供了类似于天然产物的结构。使用稀有的 pleiocarpamine 作为起始吲哚，使得比莱啡碱及其生物合成前体 voacalgine A 的首次合成成为可能。在我们的研究过程中，通过二维 NMR 对后者的结构进行了重新分配，显示出异吲哚并[3,4-b]吲哚啉的结构，而不是苯并呋喃[2,3-b]吲哚啉。
