Racemic trans-3-hydroxycarbonyl-6-(phenylacetamido)carbapenem 13 and trans-3-phosphono-6-(phenylacetamido)carbapenem 17 were synthesized. Formation of the carbapenem nuclei in 13 involved an internal Wittig reaction of the corresponding monocyclic β-lactam 10 using NaH in THF. The key step in the transformation of carbapenam 15 to 3-phosphonocarbapenem 17 involved either a decarboxylative-bromination reaction and subsequent elimination or a bromination reaction followed by decarboxylative-elimination. Carbapenem 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. aeruginosa 18S-H, and Xanthomonas maltophilia GN 12873. Like imipenem ((+)-3), carbapenem 13 was not stable to X. maltophilia oxyiminocephalosporinase type II. Its phosphonate analog 17, however, was neither a significant antibacterial agent nor a good β-lactamase inhibitor.
Date:
2005
Relation:
International Journal of Scientific Research. 2005;14:59-70
