Synthesis of new aryl substituted 5-alkylidene-2(5H)-furanones

Abstract

The rapid emergence of bacterial resistance in recent years has demanded the development of new drugs and therapies with novel modes of action to supplement existing antibiotics. Brominated furanones or fimbrolides are a promising class of quorum sensing inhibitors that inhibit biofilm formation and the expression of virulence in in vitro and in vivo models. We report here an efficient synthesis of novel brominated 5-alkylidenefuran-2(5H)-ones, making use of γ-oxo-α,β-dibromoalkanoic acid 7 as the key intermediate. Brominated furanones were subjected to the Suzuki-Miyaura cross-coupling reaction to generate a library of novel aryl furanones. This methodology may be readily adapted to the synthesis of a wide variety of substituted furanones.

Design, Synthesis, and Biological Activity of Novel 5-((Arylfuran/1H-pyrrol-2-yl)methylene)-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-4-ones as HIV-1 Fusion Inhibitors Targeting gp41

“…2-Aryl-5-formylfurans 9a − e , k − n were obtained in 29−60% yields by palladium-catalyzed Suzuki−Miyaura cross-coupling , of 5-formyl-2-furylboronic acid 8 with the corresponding aryl bromides 5a − e , k − n by modification of a literature method . Reactions of 5-bromopyrrole-2-carboxaldehyde 7 with 3-carboxyarylboronic acids 5f − j used a modification of Bumagin’s method to give 2-aryl-5-formylpyrroles 9f − j (65−86%) (Scheme , Table ).…”