Synthesis and biological evaluation of an electronically activated isooxacephem Original Research Article

New isooxacephem (±)-3-ethyl 2-hydrogen (6RS,7RS)-8-oxo-7-(phenylacetamido)-4-oxa-1-azabicyclo[4.2.0]oct-2-ene-2,3-dicarboxylate (8) was synthesized from (±)-dibenzyl 2-[cis-2-oxo-3-(phenylacetamido)-4-styryl-1-azetidinyl]-2-[t-butyldimethylsiloxy(methoxycarbonyl)methyl]malonate (1) in six steps. This bicyclic β-lactam was found to possess notable biological activities against several pathogenic microorganisms in vitro, including Staphylococcus aureus 95, S. aureus FDA 209P, Escherichia coli ATCC 39188, Salmonella typhi O-901, Pseudomonas aeruginosa 18S-H, P. aeruginosa 1101-75, and Klebsiella pneumoniae NCTC 418. The electronic activation of the β-lactam moiety by an ester group plays a prominent role in the biological activity of this novel isooxacephem.