Synthesis and Antifungal Activity of 4‐ and 6‐(1H‐Pyrrol‐1‐yl) Coumarins, and their Thiocyanato Derivatives

• Published in: ChemistrySelect (Weinheim) 2019-05, Vol.4 (19), p.5398-5406
• Main Authors: Brites, Nathan P., Dilelio, Marina C., Martins, Guilherme M., Carmo, Gabriele do, Morel, Ademir F., Kaufman, Teodoro S., Silveira, Claudio C.
• Format: Article
• Language: English
• Subjects: antifungal activity; bioactive (1H-pyrrol-1-yl)-coumarins; novel heterocycles; pyrrole syntheses; selective thiocyanation
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201900842

Facile and efficient syntheses of 4‐(1H‐pyrrol‐1‐yl)‐coumarins and 6‐(1H‐pyrrol‐1‐yl)‐coumarins from the corresponding aminocoumarins are reported. The transformations were optimized and their corresponding scope and limitations were assessed. Selected (1H‐pyrrol‐1‐yl)‐coumarins were further subjected to a mild thiocyanation, undergoing selective functionalization on the pyrrole nucleus. A set of 10 differently substituted compounds was submitted to activity testing against various fungal strains. It was found that the introduction of a SCN moiety increased the antifungal activity, turning some compounds into fungicidal agents, to the point that one of the thiocyanato derivatives displayed an antifungal profile comparable to those of fluconazole and nystatin. The coupling of privileged structures results in functionally advantageous compounds. A library of 4‐ and 6‐(1H‐pyrrol‐1‐yl)‐coumarins and their thiocyanato derivatives was prepared under optimized reaction conditions. Their antifungal activity was tested against a panel of 9 clinically relevant strains of yeasts. The introduction of a SCN moiety turned some compounds into fungicidal agents, and one of the thiocyanato derivatives exhibited an antifungal profile comparable to those of fluconazole and nystatin.