Intramolecular nucleophilic amino attack in a monobactam: synthesis and stability of (2S,3S)- 3-[(2R)-2-amino-2-phenylacetamido]-2-methyl-4-oxo-1- azetidinesulfo nic acid.

The potentially orally bioavailable arylglycine-substituted monobactam, (2S,3S)- 3-[(2R)-2-amino-2-phenylacetamido]-2-methyl-4-oxo-1- azetidinesulfonic acid, was prepared as a crystalline solid. No significant antibacterial activity [i.e., MICs were greater than 128 (micrograms/mL)] was found when the monobactam was tested against Gram positive and Gram negative bacteria. Solution instability (greater than 2,000 times less stable than aztreonam) due to intramolecular nucleophilic amine attack on the beta-lactam is believed to be a contributing factor to the poor microbiological activity.