Vancomycin glycosylation

The glycal epoxide method turned out to be useful for the construction of complex 2-branched [3-aryl glycosides, which are salient features of the potent antibiotic vancomycin [75a]. Glycal epoxide glycosylation with sodium salts of indoles pro-... 

Glycosyl Phosphates Deoxy sugars, which are vital components of various biomolecules such as vancomycin, erythromycin and daunomycin are difficult to be... 

Vancomycin and teicoplanin are complex cyclic glycopeptide antibiotics (O Fig. 11). Although the structures of these compounds were elucidated decades ago, total s)mtheses of vancomycin aglycone [150,151,152,153,154,155], fully glycosylated vancomycin [156], and teicoplanin [157,158] have only recently been reported. 

It has been observed that the incorporation of lipophilic chains into vancomycin can increase the potency of the dmg [159,160,161,162]. This is best exemplified by the observation that teicoplanin retains activity against some vancomycin-resistant bacterial strains. In one early study directed at improving the efficacy of these antibiotics, Ge et al. investigated the mechanism of action of a chloro-biphenyl derivative of vancomycin that showed activity against resistant bacteria [163]. The sulfoxide method of glycosylation was utilized to achieve the desired modification of the gluco-vancomycin precursor (O Scheme 28). 

The story of the involvement of glycosyl moieties in vancomycin activity is probably one of the most illustrative and also very topical as glycosyl derivatives of vancomycin quite recently proved to be very effective against multiply resistant (even vancomycin-resistant) bacteria. 

T. Doi, A. Kinbara, H. Inoue, and T. Takahashi, Donor-bound glycosylation for various glycosyl acceptors Bidirectional solid-phase semisynthesis of vancomycin and its derivatives, Chem. Asian J., 2 (2007) 188-198. 

For example, proteinogenic and non-proteinogerhc amino acids in l- and n-config-uration are assembled in non-ribosomal peptides. (3) Decorating enzymes can add sugar moieties to the peptide or polyketide backbone resulting in complex structures like the glycosylated antibiotic vancomycin. 

Macrocyclic antibiotics such as vancomycin or teicoplanin are large molecules with several peptide-type ring structures (besides numerous phenyl rings) moreover they are glycosylated. They can be used in the normal-phase and reversed-phase mode as well. 

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