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

Authors

Nicholas Butler, University of WollongongFollow
John B. Bremner, University of WollongongFollow
Anthony C. Willis, Australian National University
Leonardo Lucantoni, Griffith University
Vicky M. Avery, Griffith University
Paul A. Keller, University of WollongongFollow

RIS ID

138697

Publication Details

Butler, N. M., Bremner, J. B., Willis, A. C., Lucantoni, L., Avery, V. M. & Keller, P. A. (2019). Desymmetrization Reactions of Indigo with Grignard Reagents for the Synthesis of Selective Antiplasmodial [1 H,3′ H]-3-Aryl-2,2′-diindol-3′-ones. Journal of Organic Chemistry, 84 11228-11239.

Abstract

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 [1H,3′H]-3-substituted 2,2′-diindol-3′-ones were synthesized by this methodology, with several showing submicromolar inhibition and exquisite selectivity against 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.