Heyns rearrangement reaction

Considering these facts, the Heyns rearrangement reaction is usually more difficult to perform than the Amadori rearrangement. 

Results of the many investigations into the mechanism of the Maillard reaction support one of two main theories. The first assumes the formation of glycosylamines which undergo the Amadori (or, for ketoses, the Heyns) rearrangement. The 1-amino-1-deoxyketose derivative (or 2-amino-2-de-... 

The first step of the reaction is the condensation of amino acids to carbon atom 1 of aldoses (or C-2 of ketoses) and the rearrangement to the keto (aldo)-sugar (Amadori or Heyns-rearrangement). 

Ketoses undergo a similar series of reactions, leading to 2-amino-2-deoxyaldoses (Heyns rearrangement). However, browning reactions of fructose differ from those of glucose, e.g., loss of amino acid or of free amino groups (casein) is much lower.28... 

Figure 3-11 Heyns Rearrangement. Source From M.J. Kort, Reactions of Free Sugars with Aqueous Ammonia, Adv. Carbohydrate Chem. Biochem., Vol. 25, pp. 311-349, 1970.

The formation of 2-arylamino-2-deoxyaldoses in the reaction of ketoses with anilines was described as the retro-Amadori reaction (called also the Heyns rearrangement)145. 

Aldoses undergo the Amadori rearrangement and subsequently turn into caramels, the natural brown food colorants, and/or heteroaromatic compounds — derivatives of pyrrole, imidazole, and pyrazine. Ketoses react similarly into ketosylamino acids or ketosylamines, which, in the first step, undergo the Heyns rearrangement (5.17-5.23). These rearrangements are the first steps of either thermal or enzymatic (the Maillard reaction) reactions resulting in the browning of food and the aroma of roasted, baked, or fried foodstuffs. 

FURTHER REACTIONS OE GLYCOSYLAMINES 6.2.1 The Amadori and Heyns Rearrangements ... 

Pilkova, L., Pokomy, J., and Davidek, J. Browning reactions of Heyns rearrangement products, Nahrung, 34, 759, 1990. 

This reaction was first reported by Heyns, probably as early as 1952. It is a rapid rearrangement of a-hydroxy imines (including a-hydroxy Schifif bases) into stable a-amino carbonyl compounds (i.e., a-ketoamines ) under nonreducing conditions and is generally known as the Heyns rearrangement. The corresponding a-ketoamines are referred to as the Heyns rearrangement products or Heyns products. ... 

The mechanism of the entry of fructose into the Maillard reaction (a series of sugar/amino acid processes in vivo) has been studied by DFT the order of reactivity for the isomers is predicted as a- > /3- > open-chain. Heyns rearrangement products are most favourable under basic conditions, possible under neutral conditions, but unfeasible at or below glycine s isoelectric point. Kinetic and activation parameters have been reported for the corresponding glucose/proline reaction. ... 

Heyns and Meinecke (1953) and Heyns and Breuer (1958) reported that the reaction of fructose proceeds via the Heyns Rearrangement, and that of glucose is via the Amadori Rearrangement. Nishibori and Kawakishi (1994) also investigated the intermediate prod-... 

The Heyns rearrangement follows, in principle, the same pattern but employs a-hydroxy ketones as starting materials. Applied to free sugars, this reaction starts from a ketose such as D-fructose (3) and proceeds via a glycosylamine to the corresponding 2-amino-2-deoxyaldoses 4 and 5 (Scheme 2). Due to the nature of the intermediate, both epimers at position C-2 can be formed. 

Heyns and co-workers made significant contributions to this field that he called Amadori like rearrangement , retro Amadori ketosylamine rearrangement and fructosylamine rearrangement . The reaction was soon termed the Carson-Heyns rearrangement and is now known as the Heyns rearrangement. 

Heyns rearrangement products are also intermediates in the non-enzymatic browning reaction of food and, similar to the Amadori rearrangement products, can enter the Maillard reaction cascade as mentioned above (Sect. 2.3). Heyns and co-workers have conducted investigations in this context [112]. 

The Heyns rearrangement suffers from the same shortcomings as the Amadori reaction (Sect. 2.6). One of the main problems is the competition between the rearrangement reaction and the hydrolysis of the initially formed ketosylamine, the latter leading back to the starting material. 

Depending on the reaction conditions, each step of the Heyns rearrangement was found to be reversible [104], so that in most cases a mixture of ketosyl-... 

The stability of the Heyns rearrangement products is considered a problem as they are free amino aldoses which are known to be more or less unstable compounds. Under the conditions for the Heyns rearrangement subsequent reactions along the Maillard reaction cascade can take place leading to a series... 

The effect of cationic metal ions on the stable adduct formation of 16a-hydroxyesterone (118) with primary amines via the Heyns rearrangement has been investigated. Around 30 different metal chlorides were probed, and it was found that Pt +, Cu +,NP+, Co and Mn + suppressed the formation of the Heyns product significantly, whereas Fe +, Gd + and Er + caused a slight increase as compared with reactions in the absence of these cations. These results suggest that the formation of Heyns rearrangement products in vivo can be reduced by several metal ions, which were implied to be useful tools to clarify the significance of the stable adduct of 118 with proteins [122]. 

An alternative preparative access to selected Heyns rearrangement products was recently reported by reaction of various hexosamine hydrochlorides, for example, glucosamine hydrochloride (4), which were reacted (Scheme 39)... 

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