An approach to broad-spectrum cephalosporins.

Based on our view that cephalosporins with potent activities share active hydrogen(s) on the alpha-carbon of the side chain acyl, we undertook to introduce beta-ketoacid moieties onto the cephalosporin structure. Thus, starting with deacetylcephalosporin C (DCPC), first made available in quantities by our own fermentation technique, 7-amino-3'-O-acetoacetyldeacetylcephalosporanic acid (7-AACA) was made accesible. Acylation of 7-AACA with various beta-ketoacids followed by substitution at the 3'-position led to 7 beta-[2-(2-aminothiazol-4-yl)acetamido]-3-[[1-(2-dimethylaminoethyl)-1H-tetrazol-5-yl]thiomethyl]ceph-3-em-4-carboxylic acid (SCE-963, cefotiam), a potent broad-spectrum cephalosporin.