title: Desmethyl Macrolide Analogues to Address Antibiotic Resistance: Total Synthesis and Biological Evaluation of 4,8,10-Tridesmethyl Telithromycin.
abstract: There is an urgent need to discover new drugs to address the pressing problem of antibiotic-resistance. Macrolide antibiotics such as erythromycin (1) are safe, broad-spectrum antibiotics used in the clinic since 1954. Herein we report the synthesis and evaluation of 4,8,10-tridesmethyl telithromycin (3), a novel desmethyl analogue of the 3rd-generation drug telithromycin (2), which is a semisynthetic derivative of 1. Analogue 3 was found to possess antibiotic activity and was superior to telithromycin (2) when tested against resistant strains of S. aureus possessing an A→T mutation at position 2058 (E. coli numbering).
authors.affiliation: Department of Chemistry, Temple University, Philadelphia, PA 19122.
authors.forename: Venkata
authors.initials: V
authors.lastname: Velvadapu
authors.forename: Tapas
authors.initials: T
authors.lastname: Paul
authors.forename: Bharat
authors.initials: B
authors.lastname: Wagh
authors.forename: Dorota
authors.initials: D
authors.lastname: Klepacki
authors.forename: Olgun
authors.initials: O
authors.lastname: Guvench
authors.forename: Alexander
authors.initials: A
authors.lastname: Mackerell
authors.forename: Rodrigo B
authors.initials: RB
authors.lastname: Andrade