Artigo Acesso aberto Revisado por pares

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

2014; American Chemical Society; Volume: 5; Issue: 10 Linguagem: Inglês

10.1021/ml500279k

ISSN

1948-5875

Autores

Dražen Pavlović, Stjepan Mutak, Daniele Andreotti, Stefano Biondi, Francesca Cardullo, Alfredo Paio, Elisa Piga, Daniele Donati, Sergio Lociuro,

Tópico(s)

Synthesis and Catalytic Reactions

Resumo

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 addition, ketolide 11o showed excellent in vitro antibacterial activity against H. influenzae strain as compared to telithromycin. These results indicate that C-21 substituted γ-lactone ketolides have potential as a next generation macrolide antibiotics.

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