Degradations and Rearrangement Reactions
2.7
415
Cataracts, a common complication in diabetics, are caused by the reaction of glucose with the
group of proteins in the lens of the eye. It is thought that the arterial rigidity common in old age
may be attributable to a similar reaction of glucose with the NH 2 group of proteins [250,272].
7.1 Mechanism of the Maillard Reaction
As illustrated in > 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 hemiacetals, whereas 40 affords, by way of 328, the hexosamine derivatives 329 and 330 (Heyns
products), also in cyclic form. The Amadori–Heyns compounds \index{Amadori–Heyns compounds}% 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].
The Amadori product from D-glucose 33 and L-proline decomposes at 130 °C in DMF to
afford 33 and D-Mannose 54, indicating the reversibility of the Amadori reaction. A kinetic
study using 33 and phenylalanine indicates that the Schiff’s base formation is the rate-determining step of the Maillard reaction [275,276].
Maltol 337 is one of the degradation products in monosaccharide solutions with amino acids
forming Amadori compounds but not in the solution of monosaccharides alone. Heated solutions of monosaccharides yield 335, the logical precursor of 337, but not 337 itself. On the
basis of the molecular mechanics calculation indicating that 335 adopts the conformation unfavorable for dehydration into 337, a possible route via the dehydrated product 336, an orthoelimination product, has been postulated as a more favorable alternate reaction pathway [277].
7.2 Chemistry of Biologically Significant Maillard Products
In biological systems, Amadori products formed from aldoses and the amino group in peptides, decompose to release reactive sugar derivatives that are irreversibly consumed in the
production of the advanced glycation end products (AGEs). In this sense, 338 is one of the
key substances in the Maillard reaction [278]. A new specific assay of 338 has been developed using diaminonaphelene [279]. The dicarbonyl compounds 338 and 339, the suggested intermediates in the degradation of the Amadori compound 331, had been trapped with
aminoguanidine [280,281]. The role of 338 generated in the Maillard cascade as a cross-linker
of proteins has been emphasized [282]. Oxygen and metal cations accelerate the degradation of
Amadori products to D-glucosone (340), a precursor of glyoxal 341 [283,284] ( > Scheme 66).
It is known that some Maillard products have strand-breaking activities to DNA. Many compounds found in foodstuffs are α,β-unsaturated ketones [285,286]. Compounds 53, 342, 343,
and 335 ( > Fig. 9) cleave DNA single strands by generating hydroxyl radicals and other active
oxygen radicals in the presence of Fe 3+ and oxygen [287,288,289,290,291,292]. For example,
the key hydrolyzate 344 generates hydroxyl radicals and the oxidation products 345 and 346.
An organic hydroperoxide 347, presumably formed via direct oxidation of 339 or stepwise
from 348, the precursor of 335, has been isolated [293,294,295,296,297] ( > Scheme 67).
2.7
415
Cataracts, a common complication in diabetics, are caused by the reaction of glucose with the
group of proteins in the lens of the eye. It is thought that the arterial rigidity common in old age
may be attributable to a similar reaction of glucose with the NH 2 group of proteins [250,272].
7.1 Mechanism of the Maillard Reaction
As illustrated in > 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 hemiacetals, whereas 40 affords, by way of 328, the hexosamine derivatives 329 and 330 (Heyns
products), also in cyclic form. The Amadori–Heyns compounds \index{Amadori–Heyns compounds}% 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].
The Amadori product from D-glucose 33 and L-proline decomposes at 130 °C in DMF to
afford 33 and D-Mannose 54, indicating the reversibility of the Amadori reaction. A kinetic
study using 33 and phenylalanine indicates that the Schiff’s base formation is the rate-determining step of the Maillard reaction [275,276].
Maltol 337 is one of the degradation products in monosaccharide solutions with amino acids
forming Amadori compounds but not in the solution of monosaccharides alone. Heated solutions of monosaccharides yield 335, the logical precursor of 337, but not 337 itself. On the
basis of the molecular mechanics calculation indicating that 335 adopts the conformation unfavorable for dehydration into 337, a possible route via the dehydrated product 336, an orthoelimination product, has been postulated as a more favorable alternate reaction pathway [277].
7.2 Chemistry of Biologically Significant Maillard Products
In biological systems, Amadori products formed from aldoses and the amino group in peptides, decompose to release reactive sugar derivatives that are irreversibly consumed in the
production of the advanced glycation end products (AGEs). In this sense, 338 is one of the
key substances in the Maillard reaction [278]. A new specific assay of 338 has been developed using diaminonaphelene [279]. The dicarbonyl compounds 338 and 339, the suggested intermediates in the degradation of the Amadori compound 331, had been trapped with
aminoguanidine [280,281]. The role of 338 generated in the Maillard cascade as a cross-linker
of proteins has been emphasized [282]. Oxygen and metal cations accelerate the degradation of
Amadori products to D-glucosone (340), a precursor of glyoxal 341 [283,284] ( > Scheme 66).
It is known that some Maillard products have strand-breaking activities to DNA. Many compounds found in foodstuffs are α,β-unsaturated ketones [285,286]. Compounds 53, 342, 343,
and 335 ( > Fig. 9) cleave DNA single strands by generating hydroxyl radicals and other active
oxygen radicals in the presence of Fe 3+ and oxygen [287,288,289,290,291,292]. For example,
the key hydrolyzate 344 generates hydroxyl radicals and the oxidation products 345 and 346.
An organic hydroperoxide 347, presumably formed via direct oxidation of 339 or stepwise
from 348, the precursor of 335, has been isolated [293,294,295,296,297] ( > Scheme 67).