Preparation and structure-activity relationships of some 6.ALPHA.-substituted penicillins.

Abstract

The influence on the antibacterial activity of introducing a 6a-methoxy group into carbenicillin, and various 6a-substituents into sulbenicillin and piperacillin was examined. Further variations of the side chain aryl group were examined in the 6a-methoxy substituted series. This led to the identification of disodium 613-(D,L-2-carboxy-2-thien-3-ylacetamido)-6a-methoxypenicillanate (5b) as a 13-lactamase stable derivative with useful activity against Enterobacteriaceae, and disodium 6~-[D-2-(4-aminophenyl)-2-sulfoacetamido]-6a-methoxypenicillanate (6e) with slightly lower activity against the Enterobacteriaceae but more active against Pseudontonas aeruginosa.

Spirocyclic penicillins

“…Reduction with zinc and ammonium chloride l 7 was free from side-chain racemisation and only (8) was isolated. However, reduction of (7) with triethylamine and hydrogen sulphide caused concomitant racemisation and both diastereoisomers, (8) and (9), were isolated in 36 and 31% yields respectively.…”

Studies on 6.ALPHA.-substituted penicillins. II Synthesis and structure-activity relationships of 6.BETA.-(2-aryl-2-sulfoacetamido)-6.ALPHA.-methoxy penicillanic acids.

“…Of particular biological interest were those derivatives which combined a 6a-methoxy group with an acid function in the 6(3-side chain (e.g., 1,2). These compounds showed in vitro activity against a broad range of Gram-negative bacteria; including ilactamase producing strains, although activity against Pseudomonas aeruginosa and Gram-positive bacteria was poor.…”