SYNTHESIS OF NEW DNA GYRASE INHIBITORS - APPLICATION OF THE DMSO OXIDATION TO THE CONVERSION OF THE AMINE INTO THE IMINE

A novel type of pyridonecarboxylic acid with a planar thiazolopyrazine -incorporated tetracyclic skeleton, -oxo-1-thia-1H-yclopenta[cd]phenal ene-9-carboxylic acid (3), was prepared. Compound 3 was a potent inhib itor of DNA gyrase and exhibited attractive antibacterial activity aga inst both Gram-positive and Gram-negative bacteria. In the course of t he synthetic studies, we have found a new oxidation method of the amin e 4 to the imine 5 with DMSO activated by trifluoroacetic anhydride or oxalyl chloride. The DMSO/trifluoroacetic anhydride method gave the b yproduct 8, an unusual (methylthio)methyl adduct. The DMSO/oxalyl chlo ride method gave the byproducts 9 and 10, a (methylthio)methyl ester, and a halogen adduct, respectively. The mechanisms of these oxidations are also discussed.