5-Benzylidene-4-Oxazolidinones are Synergistic with Antibiotics for the Treatment of Staphylococcus Aureus Biofilms

The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative treatment approaches to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms and in combination with common antibiotics are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.</div

Enaminones via Ruthenium-Catalyzed Coupling of Thioamides and α‑Diazocarbonyl Compounds

Enaminones can be prepared via the Rh₂(OAc)₄-catalyzed coupling of α-diazocarbonyl compounds with thioamides. However, rhodium is the most expensive and least abundant among the dominant precious metals used for catalysis. Furthermore, a very limited substrate scope is known for the intermolecular rhodium catalyzed coupling reaction. Therefore, there is a need to find a more economical catalyst substitute with a broad substrate scope. In this paper, we describe the use of Ru­(II) catalysts for the synthesis of enaminones. The reaction can be performed efficiently with the Grubbs first-generation catalyst or [(Ph)₃P]₃RuCl₂ in a sealed tube. Both catalysts are much less expensive than Rh₂(OAc)₄. Secondary and tertiary thioamides, when reacted with α-diazodiesters, α-diazoketoesters, α-diazodiketones, and α-diazomonoketones give enaminones. Primary thioamides give thiazole derivatives when reacted with α-diazomonoketones. However, with other diazo compounds, primary thioamides also give enaminones. All enaminones are obtained in good yields and with good diastereoselectivity. Accordingly, the method described in this paper is an efficient and economical alternative to the Rh₂(OAc)₄-catalyzed coupling process