Glucosylamines, Amadori rearrangement

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... 

Amadori also isolated the A-substituted glucosylamine before heating it in the dry state, but no advantage was gained thereby. For example, Inoue and Onodera held pure A-p-tolyl-n-glucosylamine just above the melting point at 120° and obtained only a 17% yield of the Amadori rearrangement product. However, when they added 1 millimole of acetic... 

Although there is no positive evidence in support of it, a plausible alternative to the above reaction sequence is enolization of the aldose before condensation with the amine. In such a sequence, the Y-substituted glycosylamine would not be a precursor of the aminodeoxyketose. This postulate merits investigation because, in spite of attempts to isolate Y, Y-dibenzyl-D-glucosylamine, this compound could not be found in the reaction product of D-glucose with dibenzylamine only D-glucose or the Amadori rearrangement product was isolated. ... 

In contrast to the Amadori rearrangement products, the JV-aryl-n-glu-cosylamines are relatively stable in alkali. They do not readily liberate the amine, for their solutions give a constant optical rotation while remaining colorless in alkali over extended periods. - e, 7 However, the N-alkyl-n-glucosylamines are much more labile than the V-aryl derivatives in alkali 85, 86, 87... 

A most interesting application having commercial value is the formation of surface-active derivatives by the condensation of hydrophilic sugars with fatty amines. Only Amadori rearrangement gave hydrolysis-resistant compounds, displaying a considerable decrease in the surface tension of water, in contrast to the glucosylamine derivatives. 

This mechanism was developed mainly on the basis of experiments with A-aryl D-glycosylamines and, served a purpose to explain (a) the catalytic effect of carboxylic acids (b) the absence of die Amadori rearrangement in neutral medium" or for A-aryl D-glucosylamines derived from weakly basic amines such as dinitroaniline or indole "" (c) enoUzation, rattier ttian a 2,1-hydride shift, as ttie rate-determining step." ... 

Indeed, hydrochloric acid failed to catalyze formation of l-deoxy-l-/ -tolylamino-D-finctose from A- -tolyl-D-glucosylamine in methanol at 100 °C, while all carboxylic acids tested gave 8-40% yields of the Amadori rearrangement product, and even better yields were provided by the respective carboxylate potassium salts." ... 

An important conclusion concerning the secondary role of acid-catalysis kinetics in the Amadori rearrangement of protein-derived D-glucosylamines was put forward by Gil et al. The rate of hemoglobin glycation by D-glucose at 37 °C was found to be... 

S. KoUca and J. Sokolowski, Kinetics of the Amadori rearrangement of iV-D-glucosylamines, Rocz. Chem., 48 (1974) 439-444. 

The Amadori rearrangement also occurs for the glycosylamine derivatives of some secondary alkylamines and of primary and secondary aralkyl-amines it occurs in alcoholic solution in the presence of compounds such as ethyl malonate and acetylacetone which contain active hydrogen atoms 66), The direct reaction product from D-glucose and dibenzylamine was actually 1-dibenzylamino-l-deoxy-D-fructose (XI) 66) and not VjV-di-benzyl-D-glucosylamine (XII) as indicated earlier by Kuhn and Birkofer 76), This rearrangement was effected without benefit of acid catalysis 70) or by the use of ethyl malonate 66), The true V,i T-dibenzylglu-cosylamine (XII) could not be isolated. 

The imine (Formula 4.52) formed by the reaction of glucose with the amine is easily converted to the cyclic hemiaminal, a- and P-glucosylamine. However, N-glycosides of this type are relatively instable because they very easily mutarotate, i. e., they are easily hydrolyzed via the open-chain imine or are converted to the respective a- and P-anomer. However, the Amadori rearrangement leads to furanose, which as a hemiacetal, has a stability to mutarotation comparable with that of carbohydrates. 

Kuhn and Dansi determined that Amadori s stable isomer is not a Schiff base but the product of a molecular rearrangement. They also proved that the labile isomer is in fact the i f-substituted glucosylamine. However, they assumed incorrectly (on the basis of C-methyl analyses) that the sugar moiety of the stable isomer contained a branched-carbon skeleton. 

The most extensive part of this Section collects the Amadori compounds of D-fructose, that is, the l-amino-l-deoxy-n-fructoses. These substances, derivatives of the amino sugar isoglucosamine, are known to be rearrangement products of D-glucosylamines. Many problems, reviewed by Hodge (see Ref. 251), regarding their structure and possible mode of formation have been solved during the past few years. 

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