868684-99-5Relevant academic research and scientific papers
Design and synthesis of 16-membered cyclopeptides active against vancomycin-resistant Enterococci (VRE)
Zhu, Jieping
, p. 916 - 920 (2014/01/23)
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
Design and synthesis of simple macrocycles active against Vancomycin-resistant Enterococci (VRE)
Jia, Yanxing,Ma, Nianchun,Liu, Zuosheng,Bois-Choussy, Michele,Gonzalez-Zamora, Eduardo,Malabarba, Adriano,Brunati, Cristina,Zhu, Jieping
, p. 5334 - 5351 (2008/03/13)
16-membered meta,para-cyclophanes mimicking the vancomycin binding pocket (D-O-E ring) were designed and synthesized. The structural key features of these biaryl ether containing macrocycles are (1) the presence of β-amino-α-hydroxy acid or α,β-diamino acid as the C-terminal component of the cyclopeptide and (2) the presence of a hydrophobic chain or lipidated aminoglucose at the appropriate position. Cycloetherification by an intramolecular nucleophilic aromatic substitution reaction (S NAr) is used as the key step for the construction of the macrocycle. The atropselectivity of this ring-closure reaction is found to be sensitive to the peptide backbone and chemoselective cyclization (phenol versus primary amine) is achievable. Glycosylation of phenol was realized with freshly prepared 3,4,6-tri-O-acetyl-2-AMauroyl-2-amino-2-deoxy-α-D-glucopyranosyl bromide under phase-transfer conditions. Minimum in hibitory concentrations for all of the derivatives are measured by using a standard microdilution assay, and potent bioactivities against both sensitive and resistant strains are found for some of these compounds (MIC (minimum inhibitory concentration) 4 μgmL -1 against VRE). From these preliminary SAR studies, it was anticipated that both the presence of a hydrophobic substituent and an appropriate structure of the macrocycle were required for this series of compounds to be active against VRE.
Identification of synthetic compounds active against VRE: The role of the lipidated aminoglucose and the structure of glycopeptide binding pocket
Jia, Yanxing,Gonzalez-Zamora, Eduardo,Ma, Nianchun,Liu, Zuosheng,Bois-Choussy, Michele,Malabarba, Adriano,Brunati, Cristina,Zhu, Jieping
, p. 4594 - 4599 (2007/10/03)
A modified vancomycin binding pocket (D-O-E ring) incorporating an α-hydroxy-β-amino acid at the AA4 position is designed and synthesized. Some of these compounds display potent bioactivities against both sensitive- and resistant-strains (8 μg/ml against
