Transforming theophylline-7-acetic acid into novel beta-lactam derivatives via an unstable ketene containing imidazole moiety and assessing their antibacterial efficacy

Abstract

New β-lactams was synthesized by reacting theophylline-7-acetic acid with various Schiff bases in dry CH₂Cl₂ under a nitrogen atmosphere, utilizing the Mukaiyama reagent. The resulting β-lactams featured the theophylline moiety situated at the one position of the four-membered β-lactam ring. This approach represents a formal [2 + 2] cycloaddition of an imine to a novel ketene containing a theophyllinyl group. Remarkably, this chemoselective reaction exclusively yielded the cis-isomer of the β-lactam compound as the sole product. Subsequently, the newly synthesized compounds were evaluated for their antibacterial properties. The findings revealed that compounds 5f and 5g exhibited noteworthy antibacterial effects among the tested β-lactams. Specifically, compound 5f demonstrated activity against Staphylococcus aureus PTCC 2923, while compound 5g displayed activity against both Gram-negative bacteria and Staphylococcus epidermidis PTCC 1435.