Nuclear analogs of β -lactam antibiotics. IX. Synthesis of 7-methoxy 2-isocephems and O-2 isocephems

The syntheses of 7-methoxy-7-phenoxyacetamido-3-methyl-Δ3-isocephem-4-carboxylic acid 11a, 7-methoxy-7-phenoxyacetamido-3-rnethyl- Δ3-O-2-isocephem-4-carboxylic acid 11b and 7-methoxy-7-(2-thienyl)acetamido-3-acetoxymethyl- Δ3-O-2-isocephem-4-carboxylic acid 11c are described. A sequence analogous to that used to prepare 7-methoxy cephalosporins was used: Schiff base anions were thiomethylated and the Schiff bases hydrolyzed to free amines. The amines were acylated and thiomethyl to methoxyl conversion effected with mercuric ion catalysis. Removal of protective esters gave the acids 11a, 11b, and 11c. Compound 11c showed a modest level but broad spectrum of antibacterial activity.