Amines and aldoses

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. ... 

Reynolds, T. H. Chemistry of nonenzymic browning. I. The reaction between aldoses and amines. Adv. Food Res. 1963, 12, 1-52. 

Aromatic amines that have been used include o-toluidine, p-aminosali-cylic acid, p-aminobenzoic acid, diphenylamine and p-aminophenol. Their ability to react preferentially with a particular carbohydrate or class of carbohydrate is often useful, e.g. p-aminophenol, which shows some specificity for ketoses compared with aldoses and is useful for measuring fructose. These reagents have proved particularly useful for the visualization and identification of carbohydrates after separation of mixtures by paper or thin-layer chromatography, when colour variations and the presence or absence of a reaction aid the interpretation of the chromatogram. 

In the Maillard sequence, the initial reaction between a carbonyl group and a trivalent nitrogen atom is perhaps the most thoroughly investigated and best understood. As early as 1963, Reynolds (14) published a review with 140 references limited largely to the studies of reactions of aldoses with amines, the determination of the structures and properties of the first products of reaction (a glycosylamine), and the rearrangement of the latter to a more stable ketoseamine. 

Following the production of 1,2-enol forms of aldose and ketose amines, a series of degradations and condensations results in the formation of melanoidins. The a-fi-dicarbonyl compounds enter into aldol type condensations, which lead to the formation of polymers, initially of small size, highly hydrated, and in colloidal form. These initial products of condensation are fluorescent, and continuation of the reaction results in the formation of the brown melanoidins. These polymers are of nondistinct composition and contain... 

As indicated previously, primary and secondary amines can also react with carbonyl compounds to form a mixture of compounds containing small molecules and polymers. The small molecule compounds obtained from an aldose and an amine have the common name Amadori products because the Amadori rearrangement is involved in their formation. The compounds generated from ketoses and amines are known as Heyns products (although the differentiation Amadori/Heyns is not always considered). The mechanism for the reaction of primary amines with a reducing sugar can be formulated as follows ... 

Reactions of aldoses with amines can be stopped conveniently at the 1-amino-l-deoxy-2-ketose stage if the amine is an arylamine such as aniline (pifa 4.6) and the reaction is carried out in buffered weakly acid medium (such as glacial acetic... 

Amadori products of primary amines may react with a second molecule of aldose, and the product rearranges to form a di-n-fructose amine (see Scheme VIII), as found experimentally by Anet. Similar compounds of... 

Hydrolysis of a Schiff base to carbonyl compound and amine occurs analogously to that of oximes and hydrazones. It is dependent on the basicity of the amine and the reactivity of the aldehyde into which the azomethine is cleaved. Hydrolysis can be achieved in relatively mild conditions, e.g., by short warming in dilute mineral acid, occasionally in dilute alcohol or acetic acid. The condensation products of amines and aldoses are decomposed by even traces of acid Schiff bases are generally resistant to alkali. As in oximes and hydrazones, the aldehyde residue of Schiff bases can be replaced by another aldehyde residue there is a preference for formaldehyde in this case.620... 

As might be expected, the carbonyl function in aldoses and ketoses undergoes condensation reactions with amine derivatives (Section 17-9). For example, treatment of o-mannose with phenylhydrazine gives the corresponding hydrazone, o-mannose phenylhydrazone. Surprisingly, the reaction does not stop at this stage but can be induced to continue with additional phenylhydrazine (two extra equivalents). The final product is a double phenylhydrazone, also called an osazone (here, phenylosazone). In addition, one equivalent each of benze-namine (aniline), ammonia, and water is generated. 

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