Conventional and flow synthesis of antibiotic carbene silver derivatives

Antibiotic resistance is undermining public health; it is imperative that new classes of antibiotics are discovered and developed by companies and academic institutions alike. Previous research by this group used the excellent adaptability of N-heterocyclic carbene (NHC)-silver compounds, which allowed for the discovery of the lead compound 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene silver(I) acetate (SBC3) [1]. SBC3 breaks the methicillin-resistance in Staphylococcus aureus (MRSA) [2] and has proven effective in in vivo tests using Galleria mellonella [3]. More recently, encouraging parts of the antibiotic mechanism of SBC3 were discovered, which underlines the ability of SBC3 to break antibiotic resistance patterns [4]. And SBC3 was tested successfully against biofilms in vitro and against MRSA in-infected mice in vivo [5]. In addition, a telescoped continuous flow route was developed which surpassed the previous batch approach. This provided for a scalable means to afford the targets in higher yield.