Antimicrobial oxazolidinones

Antimicrobial oxazolidinones were successfully synthesized with the help of single-mode microwave heating on a polystyrene resin. In this case, the use of commercial multimode ovens was associated with inconsistent yields and purities, presumably due to the nonhomogeneity of the heating and a lack of sufficient temperature and pressure controls. A representative reaction is presented in Scheme 61. These solid-supported reactions proceeded smoothly in 5-10 minutes, with the boronic acid added in six equivalents and a small library with variations in both the N-acyl and the biaryl functionalities was created [145]. 

Scheme 61 Polymer-supported synthesis of antimicrobial oxazolidinones...

Antimicrobial oxazolidinones have been successfully synthesized by means of single-mode MW irradiation on a polystyrene resin. In this reaction the use of domestic multimode ovens was associated with inconsistent yields and purity, presumably because of the inhomogeneity of the MW field and lack of sufficient tern-... 

Oxazolidinones are a new class of synthetic antimicrobial agents, which have activity against many important pathogens, including methicillin-resistant Staphylococcus aureus and others. Oxazolidinones (e.g. linezolid or eperezolid) inhibit bacterial protein synthesis by inhibiting the formation of the 70S initiation complex by binding to the 50S ribosomal subunit close to the interface with the 3OS subunit. 

Combs and coworkers have presented a study on the solid-phase synthesis of oxa-zolidinone antimicrobials by microwave-mediated Suzuki coupling [38], A valuable oxazolidinone scaffold was coupled to Bal resin (PS-PEG resin with a 4-formyl-3,5-dimethoxyphenoxy linker) to afford the corresponding resin-bound secondary amine (Scheme 7.18). After subsequent acylation, the resulting intermediate was transformed to the corresponding biaryl compound by microwave-assisted Suzuki coupling. Cleavage with trifluoroacetic acid/dichloromethane yielded the desired target structures. 

Moellering R.C. (2003). Linezolid The first oxazolidinone antimicrobial. Annals of Internal Medicine 138 135-142. 

Microwave-Assisted Solid-Phase Organic Synthesis (MA-SPOS) of Oxazolidinone Antimicrobials... 

A microwave-assisted solid-phase synthesis of the antimicrobial oxazo-lidinone pharmacophore is described herein as a demonstration of the utility of this emerging technology toward drug discovery.4 The optimization process and full experimental details for the synthesis of a small library of oxazolidinones are exemplified. 

This MA-SPOS of the oxazolidinone class of antimicrobial/antibiotics allows for the rapid synthesis of libraries of compounds that simultaneously... 

The oxazolidinones are a new class of synthetic antimicrobial agents. Produced in 1987, they were found to be active in vitro against antibiotic-susceptible and -resistant cocci and did not demonstrate cross-resistance with any other antibiotics. 

Wang, D., Sherer, E., Duffy, E. A computational suite for the discovery of designer oxazolidinones suitable for IV and oral usage, in 45th Interscience Conference on Antimicrobial Agents and... 

The preparation of an antimicrobial nylon 66 material by covalent bonding to biocidal cyclic N-chloramine moieties, including hydantoins, oxazolidinones, and imidazolidinones and its properties are considered. These cyclic materials were stable over at least 3 months dry storage, and after loss of activity by reaction with reducing Na thiosulphate, the activity was easily restored by exposure to free chlorine. Biocidal swatch tests showed that nylon fabrics containing N-chlorinated hydantoin functional groups produced a 7.2 log decrease in Staphylococcus aureus and a log 7.1 decrease in Escherichia coli after a contact time of only 10 minutes. The antimicrobial nylon should have many applications, e.g. in clothing, sutures, carpets, bmshes, etc. 

Linezolid (Zyvox) is a synthetic antimicrobial agent of the oxazolidinone class. 

Dowling PM, Miscellaneous antimicrobials lonophores, nitrofurans, nitroimidazoles, rifamycins, oxazolidinones and other, in Giguere S, Prescott JF, Baggot JD, Walker RD, Dowling PM, eds.. Antimicrobial Therapy in Veterinary Medicine, 4th ed., Blackwell, Ames, lA, 2006 285-300. 

Chiral 2-oxazolidinones are an important class of heterocycles. These compounds are known for their synthetic utility as chiral auxiliaries and their pharmacological properties, specifically as antimicrobial agents. One of the most synthetically appealing methods for the synthesis of these compounds is the annulation of an acyclic precursor. In 2007, Gabriele and co-workers reported the synthesis of the 2-oxazolidinones 168 from a,a-disubstituted 2-ynylamines 167 using an unprecedented Pd-catalyzed water-promoted sequential oxidative aminocarbonylation-cyclocarbonylation process with secondary amines in the presence of carbon monoxide, oxygen, water, and potassium iodide (KI) (Scheme 78) (140). 

Quinupristin/dalfopristin and oxazolidinones have bactericidal activity against staphylococci including the methicilUn resistant strains. These would be a welcome addition to the antimicrobial arsenal should adequate clinical trials prove their efficacy. 

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