Syntheses of racemic trans-3-hydroxycarbonyl-6-(phenylacetamido)carbapenem (13), trans-3-phosphono-6-(phenylacetamlido)carbapenem (17), and P-lactam based prodrugs 19 and 22 were accomplished. Carbapenern 13 was found to possess antibacterial activity, comparable with imipenem (+)-3, against Staphylococcus aureus FDA 209P, S. aureus 95, Escherichia coli ATCC 39188, Klebsiella pneumoniae NCTC 418, Pseudomonas aeruginosa 1101-75, P. acruginosa 18S-H, and Xanthomonas inaltophilia GN 12873. Like imipenern ((+)-3), carbapenem 13 was not stable to X. inaltophilia oxyiminocephalospormase type II. Its phosphonate analog 17, however, was neither a significant antibacterial agent nor a good P-lactamase inhibitor. Chemical combinations of trans carbapenem 13 with cis carbapenem 6 (compound 19) as well as clavulanic acid (20) with cis carbapenem 6 (compound 22) via a tetrachloroethane linker exhibited remarkable activity against P-lactamase producing microorganisms in vitro. (c) 2005 Elsevier SAS. All rights reserved.
