Petasis adducts of tryptanthrin – synthesis, biological activity evaluation and druglikeness assessment. (28th July 2021)

• Record Type: Journal Article
• Authors: Brandão, Pedro; Marques, Carolina; Pinto, Eugénia; Pineiro, Marta; Burke, Anthony J.
• Is Part Of: New journal of chemistry. Volume 45:Number 32(2021)
• Page Start: 14633
• Page End: 14649
• Publication Date: 2021-07-28
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/d1nj02079j
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : The first example of a tryptanthrin-based Petasis multicomponent reaction is reported, with one of the new derivatives showing moderate fungicidal activity. Abstract : Tryptanthrin is a valuable tetracyclic alkaloid, which displays a wide variety of biological activities. The application of this type of scaffold as a starting material for the discovery of new drug candidates is of major importance in medicinal chemistry. In this work, we report one of the few examples of tryptanthrin-based multicomponent reaction approaches for drug discovery, and the first using the Petasis reaction. The optimized BINOL-catalyzed reaction conditions allowed the synthesis of a library of new tryptanthrin derivatives bearing considerable structural diversity. An asymmetric version was also established, achieving the desired enantiomerically pure derivative with 99% ee and 71% yield. The resulting library was screened against one Gram-positive and one Gram-negative bacteria, two yeasts, and three filamentous and four dermatophyte fungal strains with clinical relevance, with compound 5bea displaying moderate fungicidal activity.