Sulfa drugs–based Norbornenyl imides and reductive Heck reactions: Synthesis and antimicrobial screening

Abstract

In the field of our research interest, we designed new sulfa drugs–substituted norbornyl imides as prospective bioactive scaffolds by the reaction of endo‐endic anhydride with sulfa drugs followed by reductive Heck reactions of these products. Norbornenyl imides, as starting compounds, and their Heck products were achieved in good yields. Molecular characterization and stereochemistry of the compounds were investigated using Fourier transform infrared, liquid chromatography time‐of‐flight mass spectrometry, proton nuclear magnetic resonance, carbon 13 attached proton test, H‐H correlation spevtroscopy, and nuclear overhauser enhancement spectroscopy experiments. The Heck products of norbornenyl imides showed exo‐selectivity. All eight novel synthesized compounds, including two sulfa drugs–based norbornenyl imides and six exo‐5‐aryl‐ substituted norbornyl imides, as well as standard sulfonamides, were evaluated for antimicrobial activity against nine microorganisms consisting of Gram‐negative bacteria, Gram‐positive nonactinobacteria, actinobacteria, and yeast. The most active compound was 3a against actinobacteria. The efficacy of 2 and its derivatives against the studied strains were weaker than 3 and its derivatives, but all the studied samples exhibited antifungal potency.

N-Acylsulfonamide: a valuable moiety to design new sulfa drug analogues

“…6,7 Many research groups are still working to develop new effective and less toxic sulfa drugs that are able to circumvent the resistance developed by bacteria over the years. 8–12…”

“…6,7 Many research groups are still working to develop new effective and less toxic sulfa drugs that are able to circumvent the resistance developed by bacteria over the years. [8][9][10][11][12] Structurally close to its sulfonamide parent, the N-acylsulfonamide group exhibits an additional carbonyl that has the potential to establish new interactions with the amino acids of the DHPS active site. Furthermore, interest in N-acylsulfonamide derivatives has grown in recent years in different fields of medicinal chemistry 13 in the context of scaffold re-evolution/refining (i.e.…”