Fructose degradation mechanism

One important omission in the foregoing acid/base studies is lack of data on the acidity of the anomeric hydroxyl group, whose is 12.4 in finctose. It is the most acidic of the hydroxyl groups in fructose, it plays a crucial role in an unusual stabilization of metal complexes with D-fructose-a-amino acids, and its deprotonation is probably involved in the degradation mechanisms of fructosamine, as discussed next. 

Alkaline Degradation. At high pH, sucrose is relatively stable however, prolonged exposure to strong alkaU and heat converts sucrose to a mixture of organic acids (mainly lactate), ketones, and cycHc condensation products. The mechanism of alkaline degradation is uncertain however, initial formation of glucose and fructose apparendy does not occur (31). In aqueous solutions, sucrose is most stable at —pH 9.0. 

Richards et al.23-24 proposed that the alkaline degradation reaction proceeds via a slow, rate-determining SJCB mechanism, where the substitution at the C-l of the D-glucose moiety by oxyanions derived from l -OH or 3 -OH resulted in 1- or 3-O-P-D-glucopyranosyl-D-fructose (see Fig. 4) the mechanism implies that T - time thyl sucrose is degraded via 3 -displacement and 3 -(3-methylsucrose via the 1 -displacement. The 1- or 3-<3-[3-D-glucopyranosyl-D-fructose intermediates are then... 

Sucrose can, however, degrade to D-glucose and D-fructose in slightly alkaline solution at pH up to 8.3 (sucrose is most stable611 at pH 8.3-8.5, although the reason for this requires some elucidation), but this degradation proceeds by the normal acid-hydrolysis mechanism. In sucrose manufacture, therefore, the main reaction causing sucrose loss, between pH 7 and about 8.3, is the same acid hydrolysis that occurs at lower (acid) pH. 

Because alkali degradation of sucrose does not result in inversion products, in slightly alkaline solution (pH < 8.5), the loss of sucrose to invert sugar (glucose + fructose) is a consequence of the acid hydrolysis mechanism, which provides D-glucose and D-fructose for further alkaline degradation. 

Several products were also detected in base-degraded D-fructose solution acetoin (3-hydroxy-2-butanone 62), l-hydroxy-2-butanone, and 4-hydroxy-2-butanone. Three benzoquinones were found in the product mixture after sucrose had been heated at 110° in 5% NaOH these were 2-methylbenzoquinone, 2,3,5-trimethylbenzoquinone, and 2,5-dimethyl-benzoquinone (2,5-dimethyl-2,5-cyclohexadiene-l,4-dione 61). Compound 62 is of considerable interest, as 62 and butanedione (biacetyl 60) are involved in the formation of 61 and 2,5-dimethyl-l,4-benzenediol (63) by a reduction-oxidation pathway. This mechanism, shown in Scheme 10, will be discussed in a following section, as it has been proposed from results obtained from cellulose. 

To accommodate these facts, the earliest mechanisms proposed for degradation of D-fructose assumed that it was present in the furanose form, and that the ring remained intact. It was assumed that the initial reaction was the elimination of water, to form the 1,2-enolic form of 2,5-anhydro-D-mannose, and that further dehydration resulted in 2-furaldehyde. The necessity for D-glucose to isomerize to D-fructose was assumed to account for the much lower reaction-rate of D-glucose. This mechanism does not account for the observation that 2,5-anhydro-D-mannose is less reactive than D-fructose, nor is there any evidence that 2,5-anhydro-D-mannose is present in reacting D-fructose solutions. Nevertheless, similar mechanisms have since been proposed.13-16 Because of the ease of mutarotation of D-fructose... 

From the base-catalyzed degradation of D-fructose (pH 8.0), Shaw and coworkers147 identified 18 compounds, none of which was (a) isomeric with the starting material, or (b) a simple dehydration product. Among the products, the hydroxy-2-butanones and 1-hydroxy-2-propanone (acetol) were shown to participate in forming the carbo-cyclic products identified, but the mechanism of their formation was not elucidated. Several furan derivatives were isolated, but no lactic acid was isolated. In a similar study but with weak acid,41 most of the products were formed by a combination of enolization and dehydration steps, with little fragmentation. 

At low temperatures, D-glucose and D-fructose in the presence of ferrous sulfate are converted into D-uru/u770-hexos-2-ulose (36), which can be degraded by further oxidation to glycolic acid, glyoxylic acid, and D-erythronic acid. The nature of the products formed under various conditions and the mechanism of the reaction have been described (see Ref. 1, p. 1133). In dilute solution, in the presence of ferrous sulfate at low temperature, compound 36 gave D-ura mo-2-hexulosonic acid (37) and D-ery//zro-hexo-2,3-diulosonic acid (38). In concentrated solutions, formaldehyde was also found. The formation of these products at low temperature was ascribed to the series of reactions in Scheme 19. 

It has been postulated (37) that lactulose is formed from lactose by the Lobry de Bruyn and Alberda van Ekenstein transformation, whereby glucose is isomerized to fructose via an enol intermediate. In turn, two mechanisms have been proposed for the degradation of this intermediate (38)- One involves the addition of a proton to the enediol resulting in epimeric aldoses and the original ketose, while the other involves 8-elimination to yield galactose and saccharinic acids. The authors experimental data would tend to better support the second pathway. 

Understand the mechanisms for /V-acetylglucosamine biosynthesis and degradation of fructose and galactose, and inborn errors of metabolism associated with these pathways Appreciate the physiologic role of the glucuronate pathway and the inborn errors of metabolism associated with its malfunction ... 

The outlines of the basic mechanisms of alkaline sugar degradation were proposed by Nef, put into modern electronic form by Isbell and confirmed by a series of studies of the products of singly-O-methylated glucoses and fructose by Richards and co-workers. These studies were performed with paper chromatography as the analytical tool application of modern methods of analysis to the products of the action of calcium hydroxide at 100 °C on glucose and fructose " identified over 50 products. The main reactions can be rationalised as follows. ... 

Figure 6.11 Nef-Isbell-Richards mechanisms for degradation of glucose and fructose and the peeling reaction of 1 -> 3- and 1 ->4-linked polysaccharides. R or R can be another sugar residue, when the mechanism of the peeling reaction is illustrated.

Reaction of such compounds as ethyl acetoacetate or 2,4-pentanedione with D-fructose gives /3-substituted furan derivatives this is in contrast with the a-substituted compounds obtained from aldoses. The mechanism of reaction is identical in both cases, and the structure has been proved by degradation methods and by infrared and ultraviolet spectroscopy. With sucrose as the starting material, a mixture of a- and /8-substituted compounds was obtained in the ratio of 65 35. 

A wide range of carbohydrates is degraded by acids to furan compounds. For example, pentoses give 2-furaldehyde, and hexoses, 5-(hydroxymethyl)-2-furaldehyde (58), which may react further to yield levulinic acid. In 1910, Nef suggested the first mechanism, (55) to (58), for the formation of 5-(hydroxymethyl)-2-furaldehyde. His proposal was made at the end of his classical paper on the saccharinic acids, and was overlooked by subsequent workers and reviewers. In 1944, Haworth and Jones advanced an identical mechanism for the formation of 5-(hydroxymethyl)-2-furaldehyde from D-fructose. 

Kato, H., Yamamoto, M., and Fujimaki, M. Mechanisms of browning degradation of D-fructose in special comparison with D-glucose-glycine reaction, Agric. Biol. Chem., 33, 939, 1969. 

Further work on the mechanism of the alkaline degradation of sucrose, using substituted derivatives, supported an earlier hypothesis which invoked l-0-j3-D-glucopyranosyl-D-fructose as an intermediate (Scheme 5). ... 

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