A five-step total synthesis of the marine natural product synoxazolidinone A was achieved through a diastereoselective imine acylation/cyclization cascade. Synoxazolidinone B and a series of analogues were also prepared to explore the potential of these 4-oxazolidinone natural products as antimicrobial agents. These studies confirmed the importance of the chlorine substituent for antimicrobial activity and revealed simplified dichloro derivatives that are equally potent against several bacterial strains.

Recent efforts toward combating antibiotic resistance in bacteria have focused on Gram-positive bacteria; however, multidrug-resistant Gram-negative bacteria pose a significant risk to public health. An orthogonal approach to the development of new antibiotics is to develop adjuvant compounds that enhance the susceptibility of drug-resistant strains of bacteria to currently approved antibiotics. This paper describes the synthesis and biological activity of a library of aryl amide 2-aminoimidazoles based on a lead structure from an initial screen. A small molecule was identified from this library that is capable of lowering the minimum inhibitory concentration of β-lactam antibiotics by up to 64-fold.

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A five-step total synthesis of the marine natural product synoxazolidinone A was achieved through a diastereoselective imine acylation/cyclization cascade. Synoxazolidinone B and a series of analogues were also prepared to explore the potential of these 4-oxazolidinone natural products as antimicrobial agents. These studies confirmed the importance of the chlorine substituent for antimicrobial activity and revealed simplified dichloro derivatives that are equally potent against several bacterial strains.

Rapid Synthesis and Antimicrobial Activity of Novel 4-Oxazolidinone Heterocycles. -Oxazolidinone derivatives (VI) are synthesized by a one-step dehydration/ cyclization reaction of -keto amides (IV) bearing enolizable protons. Compounds (VI) are evaluated for their antimicrobial activity with (VIc) and (VIf) showing the best results. -(SHYMANSKA, N. V.; AN, I. H.; GUEVARA-ZULUAGA, S.; PIERCE*, J. G.; Bioorg. Med. Chem. Lett. 25 (2015) 21, 4887-4889, http://dx.

Synoxazolidinones A (Ia) and B (Ib) are screened for their antimicrobial activity against several bacterial strains (S.