Syntheses and Biological Evaluations of Highly Functionalized Hydroxamate Containing and N-Methylthio Monobactams as Anti-Tuberculosis and ß-Lactamase Inhibitory Agents.

Both the resurgence of tuberculosis (TB) and antibiotic resistance continue to threaten modern healthcare and new means of combating pathogenic bacterial infections are needed. The syntheses of monobactams possessing hydroxamate and N-methylthio functionality are described, as well as their anti-TB, in vitro ß-lactamase inhibitory, and general antimicrobial evaluations. A number of compounds exhibited significant anti-TB and ß-lactamase inhibitory activity, with MIC values in the range of 25 to < 0.19 µM against Mycobacteria tuberculosis (M.tb), and Ki values in the range of 25-0.03 µM against purified NDM-1 and VIM-1 lystate metallo ß-lactamases. This work suggests that these scaffolds may serve as promising leads in developing new antibiotics and/or ß-lactamase inhibitors.

New and concise syntheses of the bicyclic oxamazin core using an intramolecular nitroso Diels-Alder reaction and ring-closing olefin metathesis.

Herein two new and concise synthetic approaches for making an unsaturated bicyclic oxamazin core are reported. The first involves the use of an intramolecular Diels-Alder reaction to form both of the fused rings in one step. The second approach incorporates ring-closing olefin metathesis in the final step to form the second fused ring of the core. The scope of the second approach was also expanded further to afford larger ringed bicyclic systems.