N-deacetylation

Tire 2-dimethylamino derivatives 147 were prepared by a three-step reaction pathway that comprised (a) methylation of the 2-acetamido derivative 144 with methyl iodide and sodium hydride to 145, (b) mild acid-catalyzed N-deacetylation of 145 to 146, and (c) further methylation of 146 to the 2-dimethylamino compound 147 (90JMC1230) (Scheme 57). 

It is important to note that the foregoing, biosynthetic-polymer modification is usually incomplete. In fact, only a fraction of the heparin precursor undergoes all of the transformations shown in Scheme 1. However, as the product of each enzymic reaction constitutes the specific substrate for the succeeding enzyme, the biosynthesis of heparin is not a random process. Thus, sulfation occurs preferentially in those regions of the chain where the amino sugar residues have been N-deacetylated and N-sulfated, and where D-glucuronic has been epimerized to L-iduronic acid.20... 

The NMR spectra have shown the formation of Schiff base as an intermediate product in the synthesis of the fully N-deacetylated oligomers from chitosan.32 The mechanism of the Schiff base reaction leading to chain cleavage and formation of 5-hydroxymethyl-2-furfural has been proposed. 

The role of N-acetoxy arylamides as metabolically formed ultimate carcinogens jji vivo also appears to be limited. Their enzymatic formation via peroxidation of N-hydroxy arylamides can be excluded since tissues containing high levels of peroxidases such as the rat mammary gland (83) and the dog urinary bladder (84) do not form acetylated carcinogen-DNA adducts in vivo (63). Their non-enzymatic formation by reaction of acetyl coenzyme A with N-hydroxy arylamides (6 ) cannot be excluded however, even if formed, their direct reaction with cellular DNA appears unlikely as treatment of cultured cells with synthetic N-acetoxy AAF (85,86) results primarily in deacetylated arylamine-DNA adducts, apparently due to rapid N-deacetylation to form the reactive N-acetoxy arylamine (V). 

The structure of S10A has been investigated by Baddiley and coworkers.34,35 The polysaccharide is composed of D-galactose, 2-ace-tamido-2-deoxy-D-galactose, ribitol, and phosphate in the molar proportions 4 1 1 1. A hexasaccharide and its N-deacetylated derivative were obtained from S10A by treatment first with base and then... 

L-Arabinose was formed on periodate oxidation, borohydride reduction, and mild, acid hydrolysis of the pentasaccharide, demonstrating that it contains a D-galactofuranosyl residue. The amino sugar residue was resistant to periodate oxidation but was oxidized after N-deacetylation, showing that this residue is substituted at 0-4, not at 0-3. The structure of the pentasaccharide 21 was thereby established. It showed [a]D —36°, indicating that all sugar residues are /3-D-linked. 

Depolymerization of the permethylated carbohydrate is achieved by hydrolysis with acid. Under these conditions, the amino sugar residues are N-deacetylated, and the aminohexosidic linkages become resistant to hydrolysis. Stellner and coworkers29 showed that, when the acid degradation is conducted in 95% acetic acid, the amino sugar residues are also liberated, and can be analyzed by the methylation technique.29 Therefore, acetolysis followed by acid hydrolysis is now commonly used, as it allows the analysis both of hexose and hexosamine residues. 

A feasible way of introducing acid-stable linkages into carbohydrates is N-deacetylation. This can be achieved with hydrazine.59,70,71 The use of sodium hydroxide-sodium benzenethioxide in aqueous dimethyl sulfoxide for this purpose has also been described72 The difference in the acid hydrolysis of N-acetylhexosamine-con-taining carbohydrates before and after N-deacetylation was used in the study of complex glycoprotein saccharides from human erythrocyte membranes.73-75 Methylation analysis of the glycopeptides prepared... 

Preliminary hydrolysis with acetic acid may be helpful in avoiding N-deacetylation,53 and certain pneumococcal polysaccharides may be hydrolyzed with formic acid.54... 

Aliphatic aldehydes react to form monoalkylidene derivatives only in presence of potassium r-butoxide. A mechanism has been postulated that also explains the observed N-deacetylation during the formation of the product. The essential step in this is the intramolecular N - O acetyl migration in the initially formed aldol. Subsequent protonation and elimination of the acetoxy group lead to the product (Scheme 26). 

Bia was the most abundant residue representing 78.3% of the total residues, the eprinomectin Bib 8.3%, tire 24a-hydroxymethyl metabolite 7.4%, whereas the sum of the minor 24a-hydroxy-, 26a-hydroxymethyl-, and 7V-deacetylated metabolites represented less than 1.6%. The metabolism profile also indicated that eprinomectin Bj was the major residue in all edible tissues, the eprinomectin Bib representing 7.2-9.3%, whereas five to seven minor metabolites represented only 1-2% of tire total radioactivity. In muscle, however, the 7V-deacetylated metabolite accounted for as much as 3.9% of the total residues. Eprinomectin Bia was also found to be a major metabolite, accounting for 80-85.6% of the total extractable radioactivity in milk. In this matrix, the 24a-hydroxymethyl metabolite represented less than 2%, Ure N-deacetylated metabolite 0,7-2.5%, whereas the contribution by Ure other metabolites was negligible. 

The depolvmerization of N-deacetylated chondroitin sulfate, dermatan sulfate, hyaluronic acid, heparin, and heparan sulfate by nitrous acid has been studied quantitatively by reduction of the products with tritiated sodium borohydride followed by radiochromatography88 (see also, Ref. 254a). 

The rather vigorous conditions required for N-deacetylation can cause degradation.272 A recovery of 43% was reported273 for the hydrazinolysis product of chondroitin 4-sulfate, the extent of N-... 

In the literature, there are several examples of partial hydrolysis of polysaccharides or glycoconjugates containing 2-amino-2-deoxyhex-ose residues. One example is the hydrolysis of carboxyl-reduced, N deacetylated chondroitin, with the formation of 4-0-(2-amino-2-deoxy-/3-D-galactopyranosyl)-D-glucose.51 Another is the isolation of 6-0-(2-amino-2-deoxy-/8-D-galactopyranosyl)-D-galactose after N-de-acetylation and partial hydrolysis of the pentasaccharide (19) obtained... 

Bayard investigated a number of glycoproteins (aracid glycoprotein, fetuin, lactotransferrin, transferrin, and ovomucoid) by N-deacetylation followed by deamination.176 They all gave the oligosaccharides 108 and 109, demonstrating the presence of common structural elements in these compounds. 

Subsequent modifications of the polymers involve extensive formation of O-sulfate esters,1903 193 197 N-deacetylation and N-sulfation,198/199 and epimerization at C5.10 In some tissues almost all GluA is epimer-ized.200 The modifications are especially extensive in dermatan, heparan sulfates, and heparin (see also p. 177).196 201 203b The modifications are not random and follow a defined order. N-Deacetylation must precede N-sulfation, and O-sulfation is initiated only after N-sulfation of the entire chain is complete. The modifications occur within the Golgi (see Fig. 20-7) but not all... 

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