Aminocyclitols

A Acetylation, O-Phosphorylation, and O-Adenylylation. A/-Acetylation, O-phosphorjiation, and O-adenyljiation provide mechanisms by which therapeutically valuable aminocyclitol antibiotics, eg, kanamycia [8063-07-8] gentamicin [1403-66-3] sisomicin [32385-11-8], streptomycia [57-92-1], neomycin, or spectinomycin are rendered either partially or completely iaactive. Thus, eg, kanamycia B [4696-78-8] (50) can be iaactivated by modification at several sites, as shown. The elucidation of these mechanisms has allowed chemical modification of the sites at which the iaactivation occurs. Several such bioactive analogues, eg, dibekacia and amikacin have been prepared and are not subject to the iaactivation hence, they inhibit those organisms against which the parent antibiotics are iaeffective (96) (see Antibacterial agents, synthetic). 

Aminoglycosides. Antibiotics ia the amiaoglycoside group characteristically contain amino sugars and deoxystreptamiae or streptamiae. This family of antibiotics has frequentiy been referred to as aminocyclitol amiaoglycosides. Representative members are streptomycia, neomycin, kanamycia, gentamicin, tobramycia, and amikacin. These antibiotics all inhibit proteia biosynthesis. 

Enzymes transferring an acetyl moiety to one specific of several amino-groups of the aminocyclitol-aminoglycoside antibiotics (e.g. gentamicin, amikacin, kanamycin) are called aminoglycoside acetyltransferases... 

Beside AAC enzymes two different enzyme classes, nucleotidyltransferases (ANT enzymes), and phosphotransferases (APH enzymes) modify the hydroxyl groups of aminocyclitol-aminoglycoside antibiotics. 

Figure 10.27 Preparation of aminocyclitol precursors by chemoenzymatic tandem reactions.

Three mechanisms of resistance to the aminoglycoside-aminocyclitol (AGAC) group of antibiotics are recognized (Shaw et al. 1993). 

Table 9.4 Examples of aminoglycoside-aminocyclitol susceptibility to modifying enzymes... 

AGAC, aminoglycoside-aminocyclitol antibiotics (see Chapter 5) CMP, chloramphenicol. 

Other medicinally useful aminoglycoside antibiotics are based on the aminocyclitol 2-deoxystrepta-mine, e.g. gentamicin Ci from Micromonospora purpurea. Although streptamine and 2-deoxystrepta-mine are actually cyclohexane derivatives, they are both of carbohydrate origin and derived naturally from glucose. 

Semisyn. cephalosp. Tetracycline Semisyn. penicillin Aminocyclitol Macrolide Aminocyclitol Semisyn. penicillin Aminocyclitol... 

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