Desmethyl Macrolides: Synthesis and Evaluation of 4,10-Didesmethyl Telithromycin.
Novel sources of antibiotics are required to keep pace with the inevitable onset of bacterial resistance. Continuing with our macrolide desmethylation strategy as a source of new antibiotics, we report the total synthesis, molecular modeling and biological evaluation of 4,10-didesmethyl telithromycin (4), a novel desmethyl analogue of the 3rd-generation drug telithromycin (2). Telithromycin is an FDA-approved ketolide antibiotic derived from erythromycin (1). We found 4,10-didesmethyl telithromycin (4) to be four times more active than previously prepared 4,8,10-tridesmethyl congener (3) in MIC assays. While less potent than telithromycin (2), the inclusion of the C-8 methyl group has improved biological activity suggesting it plays an important role in antibiotic function.
Department of Chemistry, Temple University, Philadelphia, PA 19122.
Venkata
V
Velvadapu
Ian
I
Glassford
Miseon
M
Lee
Tapas
T
Paul
Charles
C
Debrosse
Dorota
D
Klepacki
Meagan C
MC
Small
Alexander D
AD
Mackerell
Rodrigo B
RB
Andrade