Synthesis and antibacterial activity of the tricyclic ketolides TE-802 andits analogs

The novel 6-O-methyl tricyclic ketolides, TE-802 and its analogs were synth esized by two successive cyclization reactions, 11,12-cyclic carbamate form ation by intramolecular Michael addition and 9,11-diazaheptene ring constru ction by intramolecular dehydration reaction. These new tricyclic ketolides exhibited good in vitro antibacterial activity against not only erythromyc in-susceptible strains but also erythromycin-resistant Staphylococcus aureu s and Streptococcus pneumoniae, which are problematic pathogens of nosocomi al and community-acquired respiratory tract infections, respectively.