Desmethyl Macrolides: Synthesis and Evaluation of 4,8,10-Tridesmethyl Telithromycin

作者：Velvadapu Venkata; Paul Tapas; Wagh Bharat; Klepacki Dorota; Guvench Olgun; MacKerell Alexander Jr; Andrade Rodrigo B^*

来源：ACS Medicinal Chemistry Letters, 2011, 2(1): 68-72.

DOI：10.1021/ml1002184

• Total synthesis
• ketolide antibiotics
• antibiotic resistance
• telithromycin
• desmethyl
• analogues

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 third-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 Staphylococcus aureus possessing an A -> T mutation at position 2058 (Escherichia coli numbering).

• 出版日期2011-1