Total Synthesis of Desmethyl Macrolide Antibiotics

Macrolide antibiotics occupy a special place in the history of organic chemistry and medicine. This account chronicles the evolution of our approach that ultimately led to the successful total syntheses of four desmethyl (i.e., Me -> H) analogues of telithromycin, a semisynthetic derivative of the flagship macrolide antibiotic, erythromycin. 1 Introduction 2 Project Rationale and Retrosynthetic Analysis 3 Lessons Learned from the Total Synthesis of 4,8,10-Tridesmethyl Telithromycin 4 Total Synthesis of 4,10-Didesmethyl Telithromycin 5 Total Synthesis of 4,8-Didesmethyl Telithromycin 6 Total Synthesis of 4-Desmethyl Telithromycin 7 Biological Evaluation of Desmethyl Telithromycin Analogues 8 Concluding Remarks