Vancomycin chemistry

Chemistry, biology, and medicine of glycopeptide antibiotics, in particular synthesis of vancomycin 99AG(E)2096. 

The most prominent application of the Ru-arene chemistry has been for the preparation of biaryl ethers in the syntheses of portions of vancomycin,467 ristocetin (Equation (127)),462,468-473 and teicoplanin (see also Section 10.14.1.2).474-476 Additional applications477-479 have included the syntheses of the macrocyclic biaryl ether-containing compounds K-13480,481 and OF4949-III,481,482 several macrocyclic depsipeptides,483,484 and poly(phenylene oxide) polymers.485... 

NaCNBH3 (10 mM) in phosphate buffer (pH = 3). The slurry is sonicated for 1 h, centrifuged, and the cyanoborohydride solution eliminated. The modified silica is washed with water and methanol, and then dried. This chemistry of binding provided for vancomycin a substantial bonding density of 120 p,mol/g (0.40 p,mol/m ) [70] (see Table 2.2). Surface coverage data for ristocetin A [75] and glycopeptide MDL 63,246 [43,44] were not provided by the authors. 

Another factor that remarkably affects the enantioresolution of given enantiomeric pairs has been shown to be the binding chemistry used for the silica immobilization of glycopeptides (see Section 2.2). This was illustrated in the case of ristocetin A, which was covalently bonded to silica microparticles by immobilization onto epoxy-activated silica under mild conditions [22], and compared with the corresponding commercially available CSP, where the macrocycle was immobilized as previously reported for vancomycin, rifamycin B, thiostrepton [7], and teicoplanin [30]. The comparison proved that immobilization of ristocetin A onto epoxy-activated silica could significantly improve the enantioselectivity and the resolution of the corresponding CSP in the separation of a-amino acids under RP conditions [22]. 

As an example of amino acid synthesis, let us consider approaches to the constituents of the antibiotic vancomycin (7), where a variety of methods have been used. This section outlines some of the approaches that have used chiral auxiliaries and takes from a number of approaches rather than describing a complete synthetic sequence. One amino acid residue has been prepared by lactim chemistry, where an amino acid is used as the auxiliary (Scheme 2.7).22... 

Nicolaou KC, Cho SY, Hughes R, Winssinger N, Smethurst C, Labischinski H, Endermann R, Solid and solution phase synthesis of vancomycin and vanxcomycin analogues with activity against vancomycin-resistant bacteria, Chemistry, 7(17) 3798-823, 2001. 

THE CHEMISTRY AND BIOLOGY OE VANCOMYCIN AND OTHER GLYCOPEPTIDE ANTIBIOTIC DERIVATIVES... 

Heck AJ, Bonnici PJ, Breukink E, Morris D, Wills M. Modification and inhibition of vancomycin group antibiotics by formaldehyde and acetaldehyde. Chemistry 2001 7(4) 910-16. 

Other cla.sses of therapeutically important compounds that have been. synthesized successfully by u.sing solid-pha.se combinatorial chemistry include carbohydrates and natural products. Polysaccharides ate important for various carbohydrate-protein interactions. Carbohydrate antibiotics, including vancomycin and aminoglycosides, have been the targets of combinatorial chemistry, as well as complex oligosaccharides like the one shown in Figure 3-9." A vari-... 

Figure 7 Illustration of CE-UV for identification of peptides binding to vancomycin by using affinity recognition in CE. How the concentration of vancomycin in the electrophoresis buffer (20 mM phosphate, pH 7.4) affects the electrophoretic mobility of Fmoc-Gly-D-Ala-D-Ala (L, black circles) but not Fmoc-Gly-L-Ala-L-Ala (open circles). Specific conditions indicated elsewhere (86a). (Reproduced with permission of the copyright holder, publisher and Journal of Organic Chemistry.)...

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