Antibiotics glycosylated derivatives

Salas JA, Mendez C (2005) Biosynthesis pathways for deoxysugars in antibiotic-producing actinomycetes isolation, characterization and generation of novel glycosylated derivatives. J Mol Microbiol Biotechnol 9 77-85... 

A recent example involves the synthesis of N-glycosyl derivatives of polyene macrolide antibiotics, such as the preparation of N-(deoxyfructosyl)nystatin (128) by reaction of nystatin with (+)-glucose (Scheme 30)."°... 

N-Glycosyl derivatives of daunorubicin have been prepared by direct condensation of the free sugar with the antibiotic these... 

Polyene antibiotics which possess a free amino group, e.g. amphotericin B, react with carbohydrates or their derivatives under appropriate conditions, yielding A -glycosyl derivatives. These derivatives formed water-soluble salts. The N-glucosyl and -glucuronyl derivatives showed similar antifungal activity to the parent compound but reduced systemic toxicity [398,399] and proved effective when administered intraperitoneally in the treatment of experimental candidiasis in mice [400]. 

Yoon and co-workersusing /hh couplings and NOE correlations, have identified L-olivose and o-boivinose in new glycosylated derivatives of macrolide antibiotic YC-17 produced by S. venezuelae mutant strain YJ003/pLOLV2. 

Perez M, Baig I, Brana AF et al (2008) Generation of new derivatives of the antitumor antibiotic mithramycin by altering the glycosylation pattern through combinatorial biosynthesis. ChemBioChem 9 2295-2304... 

Cell-free systems capable of in vitro synthesis of 6-methylsalicylic acid (6-MS A) and a related tetraketide, orsellinic acid, were developed long before the advent of recombinant DNA technologies in the field of natural product biosynthesis [113-115] (Fig. 5). Since then, the biosynthetic mechanisms and molecular recognition features of 6-methylsalicylic acid synthase (6-MSAS) have been extensively studied. 6-MSAS initiates synthesis with an acetyl group derived from acetyl Co A, extends the polyketide chain to a tetraketide via three decar-boxylative condensations of malonyl CoA-derived extender units, and uses NADPH to specifically reduce one of resulting carbonyls to a hydroxyl group. In its natural producer, Penicillium patulum, the product, 6-MSA is subsequently glycosylated to form the antibiotic patulin [116]. 

Whitney and coworkers [48] reported diastereoselective reactions between chiral nitrones and chiral dipolarophiles. The reaction of Vasella s nitrone 56 with the protected vinylglycine derivative 57 afforded isoxazolidines 58 with high diastereoselectivity (19 1) (Scheme 10.19). After removal of the glycosyl residue, the major isoxazolidine was converted into the antibiotic acivicin [48]. 

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