Aldosylamines

The initiating reaction between aldoses and amines, or amino acids, appears to involve a reversible formation of an N-substituted aldosyl-amine (75) see Scheme 14. Without an acidic catalyst, hexoses form the aldosylamine condensation-product in 80-90% yield. An acidic catalyst raises the reaction rate and yet, too much acid rapidly promotes the formation of 1-amino-l-deoxy-2-ketoses. Amino acids act in an autocat-alytic manner, and the condensation proceeds even in the absence of additional acid. A considerable number of glycosylamines have been prepared by heating the saccharides and an amine in anhydrous ethanol in the presence of an acidic catalyst. N.m.r. spectroscopy has been used to show that primary amines condense with D-ribose to give D-ribopyrano-sylamines. ... 

Scheme 14.—Formation of A-Substituted Aldosylamine by the Carbonyl-Amine Reaction.. ...

The next step of the Maillard sequence involves the conversion of the -substituted aldosylamine (74 75) into a 1-amino-l-deoxy-2-ketose... 

Another possible mechanism7 for the transformation of sugars with amino acids into colored products is through the Amadori rearrangement,44 which is the isomerization of an aldosylamine to a ketose derivative, for example, of a D-glucosylamine derivative to a derivative of 1-amino-l-deoxy-D-fruc-tose. Such a conversion has been shown to occur when an amino acid reacts... 

Lysine present as a SchifFs base or aldosylamine is biologically available as demonstrated with synthetic free SchifFs bases (c-benzylidenelysine and c-salicylidenelysine) (9,28) (see Table I). This can be explained by the reversibility of the reaction with the subsequent regeneration of lysine, probably in the acid medium of the stomach. 

A large number of iV-substituted aldosylamines have been synthesized by the above methods, but only a few A -substituted ketosylamines have yet been made. These have been found difficult to prepare, and the yields have been poor. Recently, however, Barry and Honeyman have described an improved method for preparing A -phenyl- and A -p-tolyl-n-fructosyl-amines, in which the amine and n-fructose are heated in anhydrous ethanol with a catalytic quantity of amine hydrochloride. Yields of up to 70% (based on the unrecovered sugar) result when the duration of reaction is short (seven minutes), and well characterized compounds have been obtained for the first time. In a similar manner, Helferich and Portz have isolated Y-p-hydroxyphenyl- and Y-p-methoxyphenyl-n-fructosylamine in yields of about 20%. 

Under certain conditions, aldosylamines undergo a transglycosylation, in which the amine residue is replaced by another amine residue. Kuhn and Dansi obtained Y-p-tolyl-n-glucosylamine by reaction of Y-(4,5-dimethyl-2-nitrophenyl)-D-glucosylamine with p-toluidine. Further ex-... 

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. 

The reaction to be discussed here is the isomerization of an aldosylamine to a l-amino-l-deoxy-2-ketose. This rearrangement was named after... 

In 1937, the true structure of the rearranged product was reported by Kuhn and Weygand. Amadori s stable isomers were shown to be unbranched A-substituted l-amino-l-deoxy-2-ketoses. Therefore, in a strict sense, the reaction named by Kuhn and Weygand the Amadori rearrangement is the complete conversion of a Af-substituted aldosylamine to a iV-substituted l-amino-l-deoxy-2-ketose. On this basis, simple enolization of an aldosylamine or ketosylamine to the intermediate 1,2-enolic form common to both should not be construed as the Amadori rearrangement. Also, the recently demonstrated conversion of a ketosylamine to a 2-amino-2-deoxyaldose does not come under the definition in spite of an obvious similarity to the Amadori rearrangement. 

If A-substituted 1-amino-l-deoxy-D-fructoses form ammono analogs of enediols with the same ease that D-fructose is transformed to an enediol, then dehydrogenating agents would be expected to distinguish between A-substituted aldosylamines and the corresponding Amadori rearrangement products. Such has been found to be the case. The distinction between... 

Reduction of the acetylated aldosyl azides affords the corresponding acetylated aldosylamines, as exemplified by the preparation of lri-0-acetyl-2-amino-2-deoxy-j8-D-glucopyranosylamine (31 33). 

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