N-Acetyl neomycin

There seems to be an analogy between the non-effective chitin and N-acetylated neomycin versus highly effective chitosan and neomycin in ability to reduce the serum cholesterol. Chitosan, however, does not seem to possess a variety of intestinal functions such as antibiotic and other properties specific for neoitiycin. 

Neomycin precipitates bile acids and fatty acids from micellar solutions in vitro [279] and promotes faecal excretion of bile acids in man [280], facts supporting the hypothesis that this is due to the ability of the drug to interact with bile and fatty acids during the micellar phase of lipid absorption [281]. Precipitation is more complete with taurochenodeoxycholate micelles than with taurocholate micelles and of the derivatives of neomycin studied dimethylamino-propyl neomycin was the most active, followed in order by neomycin, dodeca-iV-methyl neomycin hexamethochloride and N-methylated neomycin [281]. Hexa-N-acetyl neomycin failed to precipitate any of the micellar components. The same order of activity was found when the compounds were tested for their hypocholesterolaemic effect in newborn chicks [281]. 

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). 

To determine the relative amounts of neomycins B, C and neamine by a radio chemical method, Kaiser 2 separated the -labelled N-acetyl derivatives by paper chromatography and quantitated the chromatograms by liquid scintillation counting. A coefficient of variation of 3.6% was obtained. 

Neomycin 3 -phosphotransferase Hygromycin phosphotransferase Puromycin N-acetyl-transferase... 

Figure 7.9. The structure of kanamycins A, B and C. The arrows indicate the sites of (a) N-acetylation by kanamycin acetyltransferase and (b) phosphorylation by neomycin-kanamycin phosphotransferase...

Figure 7.10. The structure of the neomycins. The arrows indicate (a) the N-acetylation of kanamycin by acetyltransferase, and o-phosphorylation by (b) neomycin-kanamycin phosphotransferase and (c) Uvidomycin phosphotransferase...

The crude neomycin fraction was diluted with cold neomycin B sulfate, then acetylated to hexa-N-acetylneomycin, which was extracted with methanol. Final purification of this material was achieved by deionizing the resulting solution with Amberlite MB-3. Recoveries of 85 to 95 % of chromatographically pure hexa-N-acetylneomycin B were commonly obtained from "crude neomycin" in this way. The acetylated neomycins could be separated from each other and from acetylated neamine by cellulose chromatography. 

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. 

Escherichia coli R5 has a kanamydn-neomycin acetyl transferase that acetylates the 6 -amino group. However, resistance of this strain to kanamydns is very weak. Pseudomonas aeruginosa CN315 is highly resistant to these antibiotics here, 6 -N-methylation of 3, 4 -dideoxy-kanamycin B (Ref. 47) gives a compound that is active against this strain, as may be seen in Table III. 

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