Synthesis and antibacterial activity of asparagine derivatives of aminobenzylpenicillin

In order to improve the antibacterial activity of aminobenzylpenicillin, penicillin derivatives having an asparagine moiety in the 6-acyl side chain (11a approximately g, 12a, b, f, g) were synthesized. The structure-activity relationship of new penicillins, N4-alkyl-asparaginylaminobenzylpenicillins, was investigated. N4-Methyl-D-asparaginylamoxicillin (11a), TA-058, was found to possess a broad spectrum of antibacterial activity against Gram-positive and Gram-negative bacteria. In acute toxicity, TA-058 showed good tolerance in mice (LD50 greater than 10 g/kg, i.v.).