Design and Synthesis of 16-Membered Cyclopeptides Active Against Vancomycin-resistant Enterococci (VRE)

Authors

  • Jieping Zhu Laboratory of Synthesis and Natural Products, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN, CH-1015 Lausanne, Switzerland

DOI:

https://doi.org/10.2533/chimia.2013.916

Keywords:

Antibiotic, Cyclopeptide, Macrocycle, Snar reaction, Vancomycin

Abstract

The design, synthesis and antibiotic activities of the modified carboxylate binding pocket (D-O-E ring) of vancomycin (1) are summarized in this short account. The preliminary structure–activity relationship (SAR) studies indicated that both the structure of the 16-membered macrocycle including the absolute configuration of the modified AA4 unit and the presence of a hydrophobic chain were important for anti-VRE activities of these series of synthetic analogues. Compounds 9c and 9d in which the central amino acid (AA4) of vancomycin was replaced by (2R,3R)-?-hydroxy-?-amino acid and (2R,3R)-?,?-diamino acid, respectively, were found to be useful templates in searching for active compounds against both vancomycin-sensitive and -resistant strains. Two of these compounds (16d and 16n) having an elongated peptide chain at the C-terminal were found to be active against a broad spectrum of both vancomycin-sensitive (Staphylococcus aureus) and -resistant strains (E. faecium, E. faecalis).

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Published

2013-12-18

How to Cite

[1]
J. Zhu, Chimia 2013, 67, 916, DOI: 10.2533/chimia.2013.916.