Nuclear analogs of β-lactam antibiotics. Synthesis of 6,6-disubstituted acylaminopenems

Abstract

The preparation of 6α-methyl-2-methyl-6β-phenoxyacetamidopenem-3-carboxylate, 6α-methoxy-2-methyl-6β-phenoxyacetamidopenem-3-carboxylate, and 6α-methoxy-2-methyl-6β-phenylmalonylamidopenem-3-carboxylate from penicillin V and 6-aminopenicillanic acid is described. These penems have been isolated and characterized as their sodium or potassium salt. The chemical stability of the above compounds was determined as their half-life in aqueous buffer. In this way, it was found that the 6α-methyl analog was more stable than the parent 6-monosubstituted acylaminopenem while the remaining analogs were of comparable stability.