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Synthesis and Structure-Activity Relationships of ?-Amino-?-lactone Ketolides: A Novel Class of Macrolide Antibiotics.

ABSTRACT: An efficient synthesis of ?-amino-?-lactone ketolide (3) was developed, which provided a versatile intermediate for the incorporation of a variety of aryl and heteroaryl groups onto the C-21 position of clarithromycin via HBTU-mediated amidation. The biological data for this important new class of macrolides revealed significantly potent activity against erythromycin-susceptible strains as well as efflux-resistant and erythromycin MLSB-resistant strains of S. pneumoniae and S. pyogenes. In addition, ketolide 11o showed excellent in vitro antibacterial activity against H. influenzae strain as compared to telithromycin. These results indicate that C-21 substituted ?-lactone ketolides have potential as a next generation macrolide antibiotics.

SUBMITTER: Pavlovic D

PROVIDER: S-EPMC4190632 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Synthesis and Structure-Activity Relationships of α-Amino-γ-lactone Ketolides: A Novel Class of Macrolide Antibiotics.

Pavlović Dražen D Mutak Stjepan S Andreotti Daniele D Biondi Stefano S Cardullo Francesca F Paio Alfredo A Piga Elisa E Donati Daniele D Lociuro Sergio S

ACS medicinal chemistry letters 20140815 10

An efficient synthesis of α-amino-γ-lactone ketolide (3) was developed, which provided a versatile intermediate for the incorporation of a variety of aryl and heteroaryl groups onto the C-21 position of clarithromycin via HBTU-mediated amidation. The biological data for this important new class of macrolides revealed significantly potent activity against erythromycin-susceptible strains as well as efflux-resistant and erythromycin MLSB-resistant strains of S. pneumoniae and S. pyogenes. In addit ...[more]

PMID: 25313326

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