Desmethyl Macrolide Analogues to Address Antibiotic Resistance: Total Synthesis and Biological Evaluation of 4,8,10-Tridesmethyl Telithromycin

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2011 Jun 7

PMID 21643527

Citations 14

Authors

Venkata Velvadapu

Tapas Paul

Bharat Wagh

Dorota Klepacki

Olgun Guvench

Alexander MacKerell Jr

Rodrigo B Andrade

Affiliations

Soon will be listed here.

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).

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