Preparation and structure-activity relationships of some 6 alpha-substituted penicillins

The influence on the antibacterial activity of introducing a 6 alpha-methoxy group into carbenicillin, and various 6 alpha-substituents into sulbenicillin and piperacillin was examined. Further variations of the side chain aryl group were examined in the 6 alpha-methoxy substituted series. This led to the identification of disodium 6 beta-(D,L-2-carboxy-2-thien-3-ylacetamido)-6 alpha-methoxypenicillanate (5b) as a beta-lactamase stable derivative with useful activity against Enterobacteriaceae, and disodium 6 beta-[D-2-(4-aminophenyl)-2-sulfoacetamido]-6 alpha-methoxypenicillanate (6e) with slightly lower activity against the Enterobacteriaceae but more active against Pseudomonas aeruginosa.