Quinolone antimicrobial agents. 2. Methylenedioxy positional isomers of oxolinic acid

The synthesis and antimicrobial activity of the methylenedioxy positional isomers, 1-ethyl-1,4-dihydro-5,6-methylenedioxy-4-oxo-3-quinolinecarboxylic acid (9) and 1-ethyl-1,4-dihydro-7,8-methylenedioxy-4-oxo-3-quinolinecarboxylic acid (17), of oxolinic acid (18) have been accomplished. Isomer 9 was prepared by the reaction of N-ethyl-6,7-methylenedioxyisatoic anhydride with sodioethyl formylacetate [L. A. Mitscher, H. E. Gracey, G. W. Clark III, and T. Suzuki, J. Med. Chem., 21, 485 (1978)], while isomer 17 was prepared by thermal cyclization of diethyl 2-[(2,3-methylenedioxyanilino)methylene]malonate [D. Kaminsky and R. I. Meltzer, J. Med. Chem., 11, 160 (1968)]. Both of the new isomers are less active in vitro when compared to oxolinic acid (18) itself.