CONFORMATION OF MONOBACTAMS - X-RAY STRUCTURE OF 4-METHYL-3-MONOBACTAMIC ACID, AND CONFORMATIONAL STUDIES WITH THE USE OF CAMBRIDGE DATA-BASE

Crystal structure of 4-methyl-3-monobactamic acid 6, a structural precursor of aztreonam, is presented, and its intermolecular interactions are compared with those found in crystal structures of penicillins. Cambridge Crystallographic Data Base is used for studies of conformation and configuration of monocyclic beta-lactams in the solid state and comparison with penicillins. The correlation of the beta-lactam C-N versus C=O bond lengths shows that in monocyclic beta-lactams the amide bond resonance is influenced by substituents located at the nitrogen atom. The above nitrogen atom is pyramidal in penicillin derivatives and only slightly pyramidal in monocyclic beta-lactams. The four-membered beta-lactam ring is always folded ill penicillin derivatives and in most of the monocyclic compounds, with the C3-C4 bond length longer for cis substituted derivatives. Close values of intramolecular distances between groups being potential hydrogen-bond donors or accepters in penicillins and monobactams suggest the importance of residue with electron-withdrawing properties and containing oxygen atoms being hydrogen bond accepters, located in beta position to the beta-lactam nitrogen atom, for expressing biological activity.