Aminoglycoside antibiotics derivatives

Aminoglycoside antibiotics and / -substituted indoles are stained red. Pyrrole derivatives with free / -positions react at room temperature to yield blue-colored zones [11]. Exposure to the vapors of aqua regia deepens the colors. This reaction sometimes produces fluorescence [3]. The detection limit for monomethylhydrazine is 200 pg per chromatogram zone [3]. 

Aminoglycoside antibiotics la 107,270, 284,354,380,423,434 Amino groups lb 194 4-Aminohexoses, N-acetyl derivatives lb 233... 

Simple analogs of an aminoglycoside antibiotic, 2,6-dideoxy-4-0- (671) and -5-0-(2,3-dideoxy-2-fluoro-o -D-r/Z>o-hexopyranosyl)streptamine (672) were prepared by coupling of tri-O-acetyl-2-fluoro-D-glucal (666) with cyclitol derivatives 668 or 667 (through 669 and 670) as shown. 

The hydroxy groups in natural products like, for example, the macrolide antibiotics erythromycin, 1"1 and desmycosin, 2001 2011 as well as the 3-(hydroxymethyl)-2- or 3-cephems 2021 and derivatives of the amino sugar garamin 2031 have been converted into the carbamate function with CDI and amines. In the case of aminoglycoside antibiotics of the sisomicin series, thiocarbamates or dithiocarbamates have been prepared from alcohols or thiols using ImCSIm and amines.12041... 

Commercial neomycin is a complex mixture of aminoglycoside antibiotics originally isolated from a culture of Stn.tptomyc.zi, ( n.adiaz by Waksman and his co-workers in 1949. The principle components of the mixture are neomycin B(I) and neomycin C(II) together with a small quantity of neaminel, a degradation product of neomycin formerly known as neomycin A. Table 1 shows the content variability of neomycin B and C and neamine in commercial samples of neomycin as reported in the literature. Neomycins LP-A, LP-B and LP-C which chemically are the mono N-acetyl derivatives of neomycins A, B and C may also be present in small amounts. Several other minor components have recently been identified as paromamine, paromomycin I and paromomycin II. (Also known as neomycins D, E and F respectively). 

Neomycin has been separated from mixtures of other aminoglycoside antibiotics containing the 2-deoxystreptamine moiety as both the pertrimethylsilyl derivative and the N-trifluoro-acetyl pertrimethylsilyl derivative using a column of 0.75% 0V-1 on Gas Chrom q240. The procedure may be used to estimate the number of sugar moieties bound in the antibiotic as a close relationship exists between the number of rings and the retention time. 

Williams, P.D., Hottendorf, G.H. and Bennett, D.B. (1986a). Inhibition of renal membrane binding and nephrotoxicity of aminoglycosides. J. Pharmacol. Exp. Ther. 237 919-925. Williams, P.D., Laska, D.A. and Hottendorf, G.H. (1986b). Comparative toxicity of aminoglycoside antibiotics in cell cultures derived from human and pig kidney. In Vitro Toxicol. 1 23-32. 

D-Giucosamine and o-gaiactosamine, usually as A-acetyl derivatives, are part of the structures of several natural polysaccharides, whilst other uncommon aminosugars are components of the aminoglycoside antibiotics. We have also noted the occurrence of A-glycosides, where the nitrogen substitution is at the anomeric centre (see Box 12.3). 

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. 

TARGETING HIV-1 RNA WITH AMINOGLYCOSIDE ANTIBIOTICS AND THEIR DERIVATIVES... 

Table 1.19. Some aminoglycoside antibiotics which have gained significant therapeutic application. Producer microorganisms are listed in brackets. In addition to naturally produced aminoglycosides, a number of semi-synthetic derivatives have also found medical application. Examples include amikacin, a semi-synthetic derivative of kanamycin and netilmicin, an N-ethyl derivative of sissomicin...

The separation mechanism in the LC analysis of aminoglycosides is usually highly dependent on the applied derivatization technique, either precolumn or postcolumn. This is due to the fact that a prerequisite of aminoglycosides analysis is most often suitable derivatization to produce fluorescent derivatives the presence of primary amine groups in most of the aminoglycoside antibiotics enables a number of derivatives to be readily formed. 

Included in the class of macrocyclic lactones are avermectins and milbemycins, which are fermentation products possessing a 16-member cyclic lactone, a spiroketal moiety, and a disaccharide unit. Abamycin, ivermectin, doramectin, and eprinomycin are the avermectins most often available for anthelminthic treatment of livestock, whereas moxidectin is a milbemycin with worldwide acclaim as a cattle anthelminthic. Other anthelminthics currently used in food-producing animals are clorsulon, which is a benzenesulphonamide derivative praziquantel, which is a racemate derivative of pyrazino-isoquinoline and hygromycin B, which is an aminoglycoside antibiotic that exhibits anthelminthic properties. 

Examples for the use of acetals such as 3, of 3-nitropropanal (1), and of 3-nitropropanol (2) or its O-protected derivatives are given in the references.22-24 A recent, notable application from this group is a short, high-yield synthesis of l-acosamine,25 the arabino isomer of 3-amino-2,3,6-trideoxyhexoses that form part of many antitumor aminoglycoside antibiotics 26... 

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