RESUMEN
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.
Asunto(s)
Alcaloides Indólicos/síntesis química , Monoterpenos/síntesis química , Alcaloides/química , Biomimética , Reacción de Cicloadición , Teoría Funcional de la Densidad , Hidroxibenzoatos/química , Modelos Químicos , Acoplamiento Oxidativo , Óxidos/química , Compuestos de Plata/química , EstereoisomerismoRESUMEN
We report the Friedel-Crafts coupling of a tyrosine unit with tryptophan-derived pyrrolindolenium ions which are configurationally stable. The reaction allowed the stereoselective and divergent access to the required quaternary stereocenters found in diazonamide A and azonazine at the junction of the tyrosine and tryptophan units.
Asunto(s)
Dipéptidos/química , Compuestos Heterocíclicos de 4 o más Anillos/química , Indoles/química , Compuestos Onio/química , Oxazoles/química , Pirroles/química , Triptófano/química , Tirosina/química , Catálisis , Estructura Molecular , EstereoisomerismoRESUMEN
The straightforward entry to benzofuroindoline containing natural product-like scaffolds has been achieved by a challenging [3 + 2] oxidative coupling between phenols and indoles. The reaction proceeds by NIS-oxidation of the indole followed by the trapping of the resulting electrophilic intermediate by phenol.
