Glucosylamine preparation

Figure 1.117 Glucosylamine derivatives can be prepared at the reducing end of glycans or other reducing carbohydrates by reaction with ammonium carbonate. The resultant amine derivative can be used to conjugate the carbohydrate with other proteins or molecules without disturbing the cyclic character of the reducing end.

The preparation of crystalline methyl ethers of iV-phenyl- or Af-p-tolyl-aldosylamine by condensation of aniline or p-toluidine with aldose methyl ethers proceeds, in many cases, readily and quantitatively in methanolic or ethanolic solution, either at room or reflux temperature. For this reason, such derivatives are frequently used to characterize aldose methyl ethers isolated during constitutional studies on polysaccharides. For D-glucose, for example, crystalline 2-0-methyl-, 6-0-methyl-,3,4-di-O-methyl-, 2,3,4-tri-O-methyl-, 2,4,6-tri-O-methyl-, " and 2,3,4,6-tetra-O-methyl-A-phenyl-n-glucosylamine have been prepared in this way. Although anomeric forms of A -arylaldosylamine methyl ethers are possible, such anomeric pairs have not been isolated. No similar derivatives have been obtained from ketose methyl ethers. 

Niemann and Hays later showed that the oxidation of one mole of iV-acetyl-D-glucosylamine by lead tetraacetate involves the slow consumption of slightly more than two moles of oxidant, so confirming the result of periodate oxidation. Hockett and Chandler prepared an isomeric N-acetyl-D-glucosylamine, also cyclic since it gives a tetraacetate, by the action of 29 % aqueous ammonia on aldehydo-D-glucose pentaacetate or on hexa-0-acetyl- a -D-glucoheptonic nitrile. The oxidation of this isomer produced formaldehyde (isolated as its 2,4-dinitrophenylhydrazone), but... 

The same reaction was found to occur with piperazine, an aromatic secondary amine. In this case, the di-D-glucosylamine was prepared by condensation in 95% ethanol, with ammonium chloride as the catalyst. If the reaction was performed at 80-100°, an 80% yield resulted within 30 minutes. Refluxing with diethyl malonate gave the corresponding Amadori product in 35% yield. 

A. Yamamoto, C. Miyashita, and H. Tsukamoto, Amino sugars. I. Preparation of Y-acyl derivatives of 2-acetamido-2-deoxy-P-D-glucosylamine, Chem. Pharm. Bull, 13 (1965) 1036-1041. 

Strong bases probably can also catalyze rapid formation of D-glucosylamines at ambient temperatures. A classic method for preparation of iV-(D-glucosyl)-amino acids employs conversion of an amino acid into its sodium salt in water or methanol followed by introduction of D-glucose into the alkaline solution at room temperature. The reaction is complete as soon as the solid carbohydrate dissolves. Basic conditions, however, may favor a radier direct attack of an amine at the anomeric carbon, with water or anodier weak acid synchronously providing donation of a proton to 0-5. Such a mechanism may explain the inefficiency of A-aryl D-glucosylamine formation diat is observed under alkaline conditions. 

The anomeric 2,3,4,6-tetra-O-benzoyl-D-glucopyranosyl isocyanides, prepared from the corresponding j8-D-glucosylamine by formylation and dehydration with phosphorus oxychloride, have been polymerized with nickel chloride to give two helical polymers with opposite screw orientations. ... 

With ammonium chloride as a catalyst, Frush and Isbell (3) obtained two D-galactosylamines, one as a complex with one mole of ammonia these apparently represent a- and iS-pyranoid isomers. Diglycosylamines may also form in this type of preparation, since two isomeric di-D-glucosylamines were prepared under very similar conditions (4). 

When the reaction was first applied to the sugars, amorphous products were obtained which were considered to have the Schiff base structure. By heating glucose or fructose in an alcoholic solution of aniline, Sorokin 10) was able to prepare crystalline products, although the crystallinity of iV-phenyl-D-glucosylamine is in doubt 10, 11). Many other crystalline glycosylamines are known at present in the aliphatic 5, 12) and aromatic 13,14) series of amines. 

The 1,2-anhydro-sugar (2), prepared by reaction of the corresponding glucal derivative with 3,3-dimethyl-dioxirane, has been used in the preparation of the -benayl- -D-glucosylamine (1) and the / -azide (3) (Scheme 1), A -(2-Hydroxyethyl)glycosylamines were formed in 73-... 

The IV-linked disaccharide (S) was obtained in 38% yield during an attempted O-glycosylation (with tetra-O-benzoyl-ot-D-glucopyranoyl bromide -AgOTf-colIidine)/ The N-glucosyl-enamines (6) were prepared by reaction of D-glucosylamine with the sodium salts of malondialdehyde or its a-methyl analogue. Several 2A -disubstituted 5-chloro-4-(iJ-D-... 

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