2-Substituted Penems with Amino Acid-Related Side Chains: Synthesis and Antibacterial Activity of a New Series of β-Lactam Antibiotics

Article abstract of DOI:10.1021/jm00021a013

A new series of 6-(hydroxyethyl)penems 2-substituted with amino acid-related side chains was synthesized.The nature of the amino acyl derivative proved to be crucial both from a synthetic point of view, as β-lactam ring opening can compete with C-2 nucleophilic substitution, and for antibacterial activity.Primary amino acid amides emerged as the most suitable side chains for enhancing permeability through a Gram-negative outer membrane.In vitro activity of the new 2-<(aminoamido)methyl>penems 3a-u was influenced by the nature and position of the amide moiety, the ring size for cyclic amides, and the configuration of the amino acid.Compounds bearing amides derived from small N-methyl amino acids (such as 3a) or from cyclic amino acids (such as prolinamide 3p and 4-hydroxyprolinamide 3r) showed broad spectrum in vitro activity against both Gram-positive and Gram-negative microorganisms.