Pyrrole-Based Enaminones As Building Blocks for the Synthesis of Indolizines and Pyrrolo[1,2-]pyrazines Showing Potent Antifungal Activity

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Oct 28

PMID 37894702

Authors

Diter Miranda-Sanchez

Carlos H Escalante

Dulce Andrade-Pavon

Omar Gomez-Garcia

Edson Barrera

Lourdes Villa-Tanaca

Francisco Delgado

Joaquin Tamariz

Affiliations

Soon will be listed here.

Abstract

As a new approach, pyrrolo[1,2-]pyrazines were synthesized through the cyclization of 2-formylpyrrole-based enaminones in the presence of ammonium acetate. The enaminones were prepared with a straightforward method, reacting the corresponding alkyl 2-(2-formyl-1-pyrrol-1-yl)acetates, 2-(2-formyl-1-pyrrol-1-yl)acetonitrile, and 2-(2-formyl-1-pyrrol-1-yl)acetophenones with DMFDMA. Analogous enaminones elaborated from alkyl ()-3-(1-pyrrol-2-yl)acrylates were treated with a Lewis acid to afford indolizines. The antifungal activity of the series of substituted pyrroles, pyrrole-based enaminones, pyrrolo[1,2-]pyrazines, and indolizines was evaluated on six spp., including two multidrug-resistant ones. Compared to the reference drugs, most test compounds produced a more robust antifungal effect. Docking analysis suggests that the inhibition of yeast growth was probably mediated by the interaction of the compounds with the catalytic site of HMGR of the species.

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