The synthesis and evaluation of benzofuranones as beta-lactamase substrates.
6- and 7-Carboxy-3-phenylacetamido-3H-1-benzofuran-2-one have been synthesized as potential beta-lactamase substrates and/or inhibitors. These compounds were prepared by lactonization of the corresponding, appropriately substituted phenylglycines. The latter compounds were prepared by either the Strecker or the Bücherer-Berg method. The benzofuran-2-ones were less stable in aqueous solution than the analogous acyclic phenaceturate esters but comparably stable to analogous benzopyran-2-ones. They differed from the latter compounds however in that the C-3 hydrogen of the furan-2-ones, adjacent to the lactone carbonyl group, was distinctly acidic; 7-carboxy-3-phenylacetamido-3H-1-benzofuran-2-one exists largely as an enolate at pH 7.5. The furan-2-ones were beta-lactamase substrates with reactivity very similar to the analogous acyclic phenaceturates. They were not, however, DD-peptidase inhibitors and are thus unlikely to have antibiotic activity. The structural basis for these observations is discussed.
Adediran
S A
SA
Department of Chemistry, Wesleyan University, Middletown, CT 06459, USA.
Cabaret
D
D
Drouillat
B
B
Pratt
R F
RF
Wakselman
M
M
D001572:Benzofurans / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis / Q000187:drug effects; D007700:Kinetics; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity / Q000502:physiology; D001618:beta-Lactamases / Q000737:chemistry / Q000378:metabolism*
D001572:Benzofurans; D007783:Lactones; D001618:beta-Lactamases