Antibiotics 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. 

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

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. 

TABLE 1.2. Other Classes of Aminoglycoside-Aminocyclitol Antibiotics... 

A variety of bacterial genera have been shown to produce aminoglycoside-aminocyclitol antibiotics. These include Streptomyces, Micromonospora, Bacillus, and so on. Only those compounds emanating from Streptomyces are named -mycins (e.g., tobramycin) while others are -micins (gentamicin), -osins, -asins, or -acins. The biosynthetic pathways for the aminoglycosides and the control of their expression are not well-studied. Streptomycin is the exception. 

Spectinomycin Spectinomycin, 4a,7,9-trihydroxy-2-methyl-6,8-fcw-(methylamino)-per-hydroxypyrano-[2,3-b]benzodioxan-4-one (32.7.1), which is isolated from products of the actinomycete Streptomyces spectabilis, is an aminocyclitol, yet it is not an aminoglycoside antibiotic since it does not contain either an amino sugar region or a glycoside bond [316-324]. 

Spectinomycin (Trobicin), an aminocyclitol antibiotic chemically related to the aminoglycosides, is occasionally used to treat uncomplicated gonococcal urethritis in patients who are allergic to (3-lactam. Treatment failures have occurred, however, when spectinomycin was used in gonococcal pharyngitis or systemic gonococcal infection. 

Spectinomycin is an aminocyclitol antibiotic that is structurally related to aminoglycosides. It lacks amino sugars and glycosidic bonds. 

S ATP + hygromycin B <1> (<1> responsible for resistance against hygromycin B, an aminocyclitol antibiotic [1] resistance to hygromycin B also occurs in Escherichia coli, where a plasmid encodes a hygromycin B phos-... 

Aminoglycosides and aminocyclitols are antibiotics elaborated by bacteria of the genus Streptomyces and Micromonospora (1). Streptomycin, kanamycin, ami-... 

Apramycin is a broad-spectrum aminocyclitol antibiotic and component of the nebramycin complex, produced by a strain of Streptomyces tenebrarius. Use of this antibiotic is specifically aimed at mass therapy of colibacillosis and salmonellosis in veal calves and swine. It is administered to calves by intramuscular or oral route at a dose of 20-40 mg/kg body weight/day for 5 days, and to swine via the drinking water at a dosage of 7.5-12.5 mg/kg bw/day for 7 days, or via the feed at a rate of 100 mg/kg feed for 28 days. It is further used for treatment of colibacillosis in lambs given orally at a dosage of 10 mg/kg bw/day for 3-5 days, and for treatment of E. coli septicemia in poultry administered in the drinking water at a concentration of 250-500 mg/L for 7 days. In contrast to other aminoglycosides, apramycin is not used in human medicine. 

Spectinomycin is an aminocyclitol antibiotic produced by Streptomyces spectabilis. It is indicated for use via the oral and intramuscular or subcutaneous routes in the treatment of a variety of enteric, respiratory, and other infections of cattle, sheep, swine and poultry. Recommended dosages are 7.5-12.5 mg/kg bw for intramuscular injections and 1-5 mg/bird for subcutaneous injections in poultry. Spectinomycin is frequently combined with lincomycin and administered either intramuscularly at 15 mg/kg bw to calves, sheep, and swine (15), and at... 

Selective oxidation of sec -alcohols.1 The final steps in a synthesis of spec-tinomycin (3), an aminocyclitol antibiotic, involved a selective oxidation of one of three alcohol groups of 1 to provide 2, which furnishes 3 on deprotection (H2/Pd/ C, 90% yield). This oxidation can be carried out by conversion to a tributyltin ether followed by NBS oxidation to an a-hydroxy ketone in 80% yield (crude). Alternatively, reaction with Bu2SnO provides a stannylidene acetal, which is also oxidized by NBS to 2 in high yield. 

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