Desymmetrization Reactions of Indigo with Grignard Reagents for the Synthesis of Selective Antiplasmodial [1H,3′H]-3-Aryl-2,2′-diindol-3′-ones

The nucleophilic addition of organomagnesium and organolithium species to the cheap and robust natural dye indigo led to desymmetrization of the heterocyclic nucleus via a Grignard addition-dehydration procedure. Twenty-seven diversely functionalized [1 H ,3' H ]-3-substituted 2,2'-diindol-3'-ones were synthesized by this methodology, with several showing submicromolar inhibition and exquisite selectivity agains P. falciparum parasites (3D7 and Dd2 strains) in vitro . This work demonstrates the utility of indigo dye as a highly versatile scaffold for the synthesis of structurally diverse, bioactive heterocycles.