Synthesis of 2-Carbamoyl-4-Oxo-1,5-Diazabicyclo [3.2.1] Octane Derivatives as a Possible Inhibitors of Serine β-Lactamases

Antibiotic resistance is becoming ever more severe due in part to the increasing use of antibiotic drugs. One significant contributor to this problem is the production of β-lactamase enzymes that provide resistance to common β-lactam antibiotics. The scope of this research is to synthesize and study the β-lactamase inhibitors of 2-carbamoyl-4-oxo-1,5-diazabicyclo [3.2.1] octane derivatives. Currently the research process is in the beginning stages of synthesizing three compounds: (R)-hexahydro-6-oxopyrimidine-4-carboxylic acid (1a) , hexahydro-2,2-dimethyl-6-oxopyrimidine-4-carboxylic acid (1b) and hexahydro-6-oxo-2-phenylpyrimidine-4-carboxylic acid (1c) . The future steps are to synthesize (R) -3-(methoxycarbonyl)-hexahydro-6-oxopyrimidine-4-carboxylic acid (2a) , (R)-dimethyl tetrahydro-4-oxopyrimidine-1,6(2H)-dicarboxylate (3a) and (R)-methyl hexahydro-6-oxopyrimidine-4-carboxylate (4a) . All the compounds will be evaluated for the inhibitory activities against pure TEM-1 and P99 β-lactamase.