Novel sources of antibiotics are required to keep pace with the inevitable onset of bacterial resistance. Continuingwith our macrolide desmethylation strategy as a source of new antibiotics, we report the total synthesis, molecular modeling, andbiological evaluation of 4,10-didesmethyl telithromycin (4), a novel desmethyl analogue of the third-generation drugtelithromycin (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 MICassays. While less potent than telithromycin (2), the inclusion of the C-8 methyl group has improved biological activity,suggesting that it plays an important role in antibiotic function. 

Desmethyl macrolides: Synthesis and evaluation of 4,10-didesmethyl telithromycin

244th National Meeting (2012)

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