Total Synthesis of (−)-4,8,10-Tridesmethyl Telithromycin

Novel sources of antibiotics are required to address the serious problem of antibiotic resistance. Telithromycin (<b>2</b>) is a third-generation macrolide antibiotic prepared from erythromycin (<b>1</b>) and used clinically since 2004. Herein we report the details of our efforts that ultimately led to the total synthesis of (−)-4,8,10-tridesmethyl telithromycin (<b>3</b>) wherein methyl groups have been replaced with hydrogens. The synthesis of desmethyl macrolides has emerged as a novel strategy for preparing bioactive antibiotics.