Heyns Products

As illustrated in O Scheme 65, 33 reacts with an amine to give an imine 326 that isomerizes into an aminoketose 327 (Amadori product), existing as an equilibrium mixture of cyclic hemi-acetals, whereas 40 affords, by way of 328, the hexosamine derivatives 329 and 330 (Heyns products), also in cyclic form The Amadori-He)ms compounds index Amadori-Heyns com-pounds % are at the head of the complex sequences of the Maillard reaction. The crystal structure of the Amadori product 331 between 33 and glycine has been determined more than three decades after the first proposal of its structure. Alternative preparations and X-ray analyses of Heyns products 332 and 333 have been reported [273,274]. 

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 ... 

The reaction products of the Maillard reaction, such as l-amino-l-deoxy-2-ketose (Amadori product) or 2-amino-2-deoxyaldose (Heyns product), do not contribute to flavor directly but they are important precursors of flavor compounds [48]. These thermally unstable compounds undergo dehydration and deamination reactions to give numerous rearrangement and degradation products. The thermal degradation of such intermediates is responsible for the formation of volatile compounds that impart the characteristic burnt odor and flavor to various food products. For example, at temperatures above 100 C, enolization products (such as l-amino-2,3-enediol and 3-deoxyosone) yield, upon further dehydration, furfural from a pentose and 5-hydroxy methylfurfural and 5-meth-ylfurfural from a hexose [2]. 

A. Jakas, A. Katie, N. Bionda, and S. Horvat, Glycation of a lysine-containing tetrapeptide by D-glucose and D-fiuctose— influence of different reaction conditions on the formation of Amadori/Heyns products, Carbohydr. Res., 343 (2008) 2475-2480. 

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. ... 

Ketoses react correspondingly to form Heyns products (Kurt Heyns (1908-2005), German chemist). Isomerisation of the double bond leads unselectively to a new stereogenic centre. Consequently, the products have a glucose or mannose configuration. 

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]. 

Several markers for the Maillard reaction have been described in the literature. For example, the product initially formed between glucose and lysine is partly transformed into furosine (Heyns et ah, 1968) on acid hydrolysis. Conversely, the fluorescent amino acid pentosidine (Sell and Monnier, 1989) is an advanced glycation endproduct (AGE) and may form covalent bonds between proteins (cross-linking). Furthermore, the Maillard reaction leads to an increase in characteristic fluorescence (excitation 370 nm, emission 440 nm) (Monnier et ah, 1984 Pongor et ah, 1984). 

Heyns et al. [53] started with di-O-acetyl-L-rhamnal (28) which after reaction with sodium azide in the presence of boron trifluoride etherate as Lewis catalyst gave again the four products 79-82 (R=Ac). Subsequent quenching with NIS and the aglycone led to ristosamine and acosamine glycosides 86 and 87. 

Heyns and Stumme260 have provided further evidence as to the widespread occurrence of this type of rearrangement for compounds in which the a-hy-droxy carbonyl group is either terminal or non-terminal, and a detailed electronic mechanism for this rearrangement has been put forward.264 Confirmatory evidence for the formation of products of the Amadori type... 

The Heyns synthesis of amino sugars is of particular theoretical interest since it is believed that the biosynthesis of amino sugars takes place in a related manner which involves the 6-phosphates.34 37 Considerable difficulty attends the isolation of the products, and over-all yields are often low. 

Quantitatively, the major path of degradation of the Amadori or Heyns Intermediate 1s a dehydration reaction which yields furfural and hydroxymethylfurfural. Of greater flavor significance are the minor pathways which can result in both aromatic products as well as reactive Intermediates. These Intermediates can undergo a retro-aldollzatlon reaction to produce alpha dicarbonyl compounds, such as pyruvaldehyde and diacetyl as well as reactive monocarbonyls, such as glycolaldehyde and glyceraldehyde. 

P. A. Davidse, J. L. M. Dillen, A. M. Heyns, T. A. Modro, and P. H. van Rooyen, Photochromic systems. Part 1. Structural and spectroscopic study of photochemically active products of Stobbe condensation. 2,3-dibenzylidene-succinic acid and its anhydride, Can. J. Chem., 68, 741-746 (1990). 

---