Vancomycin chemical structure

In an attempt to change and broaden the capabilities of the vancomycin CSP, the glycopeptide was derivatized with (R)- and (S )-(l-naphthylethyl) isocyanate (NEIC) and then bonded to a silica-gel support [48]. A variety of chiral compounds was tested on the two composite stationary phases and the results were compared with the ones obtained using the underivatized vancomycin CSP. The advantages of the NEIC derivatization were not as obvious or substantial as they were in the case of cyclodextrin phases [49]. Moreover, the exact chemical structures of the synthesized NEIC derivatives of vancomycin were not reported. 

Vancomycin Vancomycin (32.7.2) was isolated in 1956 from the products of the functional activity of actinomycetes Streptomyces orientalis (cnrrently Nocardia orientalis). Based on its chemical structure and contents, vancomycin is classified as a glycopeptide antibiotic. Its molecular mass is significantly more than practically any other used antibiotics [325-330]. 

Figure 1.3 Chemical structures of glycopeptides antibiotics vancomycin (1) [1], eremomycin (2) [15a], ristocetin A (3) [15b], and teicoplanin (4) [15c],...

The chemical structure of lipid II is shown, and the binding sites of vancomycin and nisin are indicated. 

FIGURE 7.1 Characterization of cell division inhibitor PC190723. (A) Chemical structure of PC190723. (B) In vivo efficacy of PC190723 in a murine model of infection. Mice were injected intraperitoneally (IP) with a lethal inoculum of S. aureus ATCC 19636 at time 0. One hour after infection the animals received 3 mg/kg (uneven dashed line), 10 mg/kg (dotted line), or 30 mg/kg (dark line) of PC190723 negative control (vehicle only, dashed black line) or 3 mg/kg of the vancomycin control antibiotic (thick dark line) by subcutaneous (SC, top) or intravenous (IV, bottom) administration. Mortality was recorded daily for 7 days. (Source From Haydon, DJ. et al. 2008. Science 321, 1673, 2008. Reprinted with permission from AAAS.)... 

Fig. 7.15 Chemical structures of the glycopeptide-type antibiotics vancomycin, teicoplanin and ristocetin A. For teicoplanin the prevalent derivative (A2-2, 85%) of the teicoplanin complex is shown.

Figure 4.16 Chemical structures of the macrocyclic glycopeptide antibiotics (a) vancomycin, (b) teicoplanin, (c) avoparcin, (d) ristocetin A, that have been used as chiral selectors in CSPs for HPLC. Reproduced from Ward and Farris, J. Chromatogr. A 906 (2001), copyright (2001), with permission from Elsevier.

Figure 6 Cooperative binding of vancomycin (filled structures in the stereo plot (c) to the cell-wall surrogate 4. The deviations in the ITC titration curves found by assuming independent binding sites (a) disappeared when the model was switched to include cooperativity. (Reproduced from Ref. 64. American Chemical Society, 2006.)...

FIGURE 5.4 Chemical structures of (a) (—)-erythromycin and (b) (—)-vancomycin hydrochloride. 

Vancomycin, a natural product that was first approved in 1955, is still the prototype for structural variations with the same mechanism of action the binding to the terminal L-Lys-D-Ala-D-Ala tripeptide in Gram-positive cell wall biosynthesis. The compounds below are semi-synthetic modifications of the same basic structural class (glycopeptides) as the prototype vancomycin, thus following in the chemical footsteps of the (1-lactams currently, there are three semi-synthetic glycopeptides, oritavancin 39, telavancin 40 and dalba-vancin 41, in late stage clinical development. 

Figure 2 A selection of nonribosomal peptides. Chemical and structural features that contribute to the vast diversity of this class of metabolites are highlighted Heterocycle (bacitracin), lactone (surfactin, daptomycin), ornithine and lactam (Tyrocidine), sugar, chlorinated aromats, C-C crosslink (Vancomycin), N-formyl groups (Coelichelin and linear gramicidin), fatty acid (daptomycin), dihydroxybenzoate and trimeric organization (bacillibactin), dimeric organization (gramicidin S), and ethanolamine (linear gramicidin).

The Gellman laboratories later reported the chemical synthesis of a 17-mer based on the 12-helix forming trani-2-aminocyclopentanoic acids [64]. Charged amine fimctionalities in combination with neutral monomer units were incorporated into the oligomer to provide an amphiphilic secondary structure (Fig. 35). When tested for bactericidal and bacteriostatic activity against a vancomycin-resistant bacterial strain, this material exhibited activity similar to that of a known 23-mer... 

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