P-bromopenicillanic acid

Penam P-Lactamase Inhibitors. Penam is the trivial name given derivatives of the penicillin nucleus (31) the chemical name of which is 4-thia-l-azabicyclo[3.2.0]heptane. Table 6 gives activity data for a diverse group of penams. The report that 6-p-bromopenicillanic acid [26631-90-3], [2(5)-(2(X,5(X,6P)]-6-bromo-3,3-dimediyl-7-oxo-4-diia-l-azabicyclo[3.2.0]lieptane-2-carboxylic acid, (31, R = Br, R = H, R" = R " = CH3) is a potent... 

Both 6-yS-bromopenicillanic acid (24) and 6-y5-iodopenicillanic acid (25) were as potent as clavulanic acid and inhibited the same range of /S-lactamase enzymes Table 6.7) [18, 43, 66], They acted synergistically with ampicillin and cefazolin to inhibit yS-lactamase containing S. aureus, those members of the Enterobacteriaceae which contain plasmid yS-lactamases such as the TEM enzyme, and a Klebsiella spp. which contains a chromosomal yS-lactamase. They did not however inhibit most of the yff-lactamases of organisms such as Enterobacter spp. Providencia spp., P. aeruginosa, or Serratia spp. Table 6.8) [66]. 

Aminopenicillanic acid (8) was converted to 6(5)-bromopenicillanic acid by trapping of the diazo-intermediate with hydrogen bromide. Esterification of the dicyclohexylamine salt (93) with p-methoxybenzyl bromide, followed by oxidation, afforded the sulphoxide (94) in 60% yield from 6-APA. Elaboration of this sulphoxide to the disulphide (96) was effected by the procedure established by Kamiya et al. [98] the sulphenic acid (95), formed by heating the sulphoxide to reflux in toluene, was intercepted by reaction with 2-mercaptobenzothiazole to yield the disulphide (96). The latter was transformed by base-catalysed double bond isomerization to the conjugated ester disulphide (97) [95% yield from (94)]. Reductive formylation of disulphide (97) then provided the formylthio-derivative (98). Cyclization of the oxalimide (99), obtained by ozonolysis of... 

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