3-Sulfonyl-1-carba-1-dethiacephems

Article abstract of DOI:10.1021/jm00131a005

The stability of the 1-carba-1-dethiacephalosporin framework has allowed the synthesis of a range of 3-sulfonyl-1-carba-1-dethiacephems unavailable for a variety of reasons in the cephem arena.The known p-nitrobenzyl 7β-(phenylacetamido)-3-<<(trifluoromethyl)sulfonyl>oxy>-1-carba-1-dethia-3-cephem-4-carboxylate served as a precursor to this series of compounds.Displacement of the enol triflate with various sulfinates in acetonitrile or DMF and deprotection of the intermediates led to 7β-<<(2-amino-4-thiazolyl)(methoxyimino)acetyl>amino>-3--1-carba-1-dethia-3-cephem-4-carboxylic acids.The 3-sulfonyl-1-carba-1-dethiacephems display potent activity against both Gram-positive and Gram-negative bacteria.The following MIC's (μg/mL) for the 3-cyclopropyl sulfone are representative: Staphylococcus aureus = 4, Streptococcus pyogenes = 1, Haemophilus influenzae = 0.25, Escherichia coli = 0.03, Enterobacter cloacae = 0.25, Proteus rettgeri = 0.25.The excellent in vitro antibacterial activity of this series indicates the potential of the carbacephalosporin framework for exploring substituents which are unknown or which produce unstable cephems.