Synthesis and antibacterial activity of 1-hydroxy-1-methyl-1,3-dihydrofuro[3,4-b]quinoxaline 4,9-dioxide and related compounds

A Free-Wilson analysis of the antibacterial activity found in a variety of quinoxaline 1,4-dioxides prepared and tested in these laboratories unexpectedly predicted that potent activity should be found in the case where the heterocyclic ring system was substituted with an acetyl group in the 2 position and a hydroxymethyl group in the 3 position (2). The synthesis and antibacterial activity of this compound, which was actually isolated in the hemiketal form (3), and of several of its derivatives are reported. 1-Hydroxy-1-methyl-1,3-dihydrofuro[3,4-b]quinoxaline 4,9-dioxide (3) possesses exceptional activity in vivo against Escherichia coli, Salmonella choleraesuis, and Pasteurella multocida.