title: The synthesis and evaluation of benzofuranones as beta-lactamase substrates.
abstract: 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.
authors.affiliation: Department of Chemistry, Wesleyan University, Middletown, CT 06459, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Adediran
authors.forename: D
authors.initials: D
authors.lastname: Cabaret
authors.forename: B
authors.initials: B
authors.lastname: Drouillat
authors.forename: R F
authors.initials: RF
authors.lastname: Pratt
authors.forename: M
authors.initials: M
authors.lastname: Wakselman
mesh_terms: 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*
chemical_list: D001572:Benzofurans; D007783:Lactones; D001618:beta-Lactamases