The synthesis and evaluation of benzofuranones as beta-lactamase substrates

6- and 7-Carboxy-3-phenylacetamido-3H-1-benzofuran-2-one have been synthesi zed as potential p-lactamase substrates and/or inhibitors. These compounds were prepared by lactonization of the corresponding, appropriately substitu ted phenylglycines. The latter compounds were prepared by either the Streck er or the Bucherer-Berg method. The benzofuran-2-ones were less stable in a queous solution than the analogous acyclic phenaceturate esters but compara bly stable to analogous benzopyran-2-ones. They differed from the latter co mpounds however in that the C-3 hydrogen of the furan-2-ones, adjacent to t he lactone carbonyl group, was distinctly acidic; 7-carboxy-3-phenylacetami do-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 inhi bitors and are thus unlikely to have antibiotic activity. The structural ba sis for these observations is discussed. (C) 2001 Elsevier Science Ltd. All rights reserved.