Vancomycin mimic

More remarkable are the cyclic peptidocalixarenes 7a,b that have been prepared as vancomycin mimics.23 In particular, compound 7b (which has the smaller ring) shows a minimum inhibitory concentration against some Grampositive bacteria, only twice as high as the concentration reported for vancomycin. 

The vancomycin mimics, 7, discussed above are an important example of biologically active calix[4]arene derivatives. In this case the whole macrobicy-clic structure including the calixarene skeleton with its cavity seems to be important for the pharmacological effect. In the following sections we discuss derivatives in which the calixarene serves more or less as an easily available scaffold for the assembly of biologically relevant fragments such as peptides or carbohydrates. 

Although the total syntheses of vancomycin and derivatives can be heralded as top achievements in organic synthesis [1], they are of course not practical for obtaining these compounds for application purposes. Therefore, there has been considerable interest in the preparation of simplified mimics of vancomycin, having especially (part of) the binding cavity for D-Ala-D-Ala. 

Synthesis of Bicyclic Peptide 9 an Alkene-bridged Mimic of the Vancomycin C-D-E Cavity... 

Recently, Zhang et al. applied RuAAC reaction to synthesize a 1,5-triazole bridged bicyclic structure as a mimic of the CDE-ring of vancomycin (Fig. 1 Id), which is a highly important glycopeptide antibiotic for treating bacterial infections... 

Zhang J, Kemmink J, Rijkers DTS, Liskamp RMJ (2013) Synthesis of 1,5-triazole bridged vancomycin CDE-ring bicycUc mimics using RuAAC macrocyclization. Chem Commun 49 4498-4500... 

Fig. 10.2 Distally-bridged peptidocalixarene mimics the mode of binding of vancomycin antibiotics by binding D-Ala-D-Ala by the suggested binding mechanism (Image from Casnati et al. [4])...

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