Aldoses degradative oxidation

RUFF - FENTON Degradation Oxidative degradation of aldoses via a-hydroxy acids to lower chain aldoses. 

These compounds are formally derived from aldoses by oxidation of a secondary hydroxyl group to a ketone group. The well-known aldos-2-uloses (usually termed simply aldosuloses or osones in former usage) have long been known in the form of their bis(hydrazone) derivatives, the osazones. Deoxyaldosuloses have been implicated as intermediates in a variety of degradation reactions. Aldos-3-, -4-, and -5-uloses have been prepared, principally as intermediates for synthesis. 

There are a number of ways in which an aldose can be converted into another aldose of one less carbon atom. One of these methods for shortening the carbon chain is the Ruff degradation. An aldose is oxidized by bromine water to the aldonic acid oxidation of the calcium salt of this acid by hydrogen peroxide in the presence of ferric salts yields carbonate ion and an aldose of one less carbon atom (see Fig. 34.3). 

Thus in the Ruff degradation, for example of o-glucose to o-arabinose, the aldose is oxidized electrolytically to the aldonic acid and this on treatment with hydrogen peroxide and ferric acetate affords the 2-ketoaldonic acid (aldosulose), which yields D-arabinose by loss of carbon dioxide. The yield of aldopentose from the aldonic acid... 

Reduction of an aldose forms one alditol reduction of a ketose forms two alditols. Br2 oxidizes aldoses, but not ketoses ToUens reagent oxidizes both. Aldoses are oxidized to aldonic acids or aldaric acids. Aldoses and ketoses react with three equivalents of phenyUiydrazine, forming osazones. C-2 epimers form identical osazones. The Kiliani-Fischer synthesis increases the carbon chain of an aldose by one carbon— it forms C-2 epimers. The Ruff degradation decreases the carbon chain by one carbon. The OH groups of monosaccharides react with acetyl chloride to form esters and with methyl iodide/silver oxide to form ethers. 

Aldoses are oxidized to aldonic acids or to aldaric acids. The Kiliani-Fischer synthesis increases the carbon chain of an aldose by one carbon it forms C-2 epimers. The Wohl degradation decreases the carbon chain by one carbon. 

The parallel synthesis of furans from a-hydroxycarbonyl compounds is frequently conducted using aldoses or ketoses as readily available sources of this functional grouping, especially as the resulting polyhydroxyalkyl side-chain can be removed easily by oxidative degradation (Schemes 67d and 67e) 56MI30300). 

WOHL DEGRADATION. Method for the conversion of an aldose into an aldose with one less carbon atom by the reversal of the cyanohydrin synthesis. In the Wohl method, the nitrile group is eliminated by treatment with ammoniacal silver oxide. 

Aldoses can be degraded by the following two reactions. First the aldehyde is oxidized with bromine water to form a carboxylic acid. Next the carboxylic acid is decarboxy-lated with hydrogen peroxide and ferric sulfate leaving an aldehyde. The new aldose is one carbon shorter. When glucose is degraded in this manner, and the product is oxidized by dilute nitric acid, an optically active compound is formed. 

Methods for the chemical synthesis of glycuronic acids include (i) reduction of the monolactones of aldaric acids, (ii) oxidation of the primary alcoholic group of aldose derivatives, (iii) oxidative degradation procedures, (iv) chain-extension reactions on dialdoses, and (v) epimerization reactions. 

Wood-degrading fungi produce a family of pyranose oxidases (EC 1.1.3.10), enzymes catalyzing the oxidation at C-2 of several aldoses. A simple and convenient conversion of D-glucose into D-arabino-hexos-2-ulose involves the use of a pyranose-2-oxidase isolated from Polyporus obtusus, which was purified and immobilized on activated CH-Sepharose 4B.446... 

Ferric ion catalyzes the formation of the hydroperoxyl radical, according to Eq. (35) such a radical appears to constitute the oxidant in the Ruff method of degrading aldonic acids to the next lower aldoses. A number of examples of the use of this reagent in the laboratory are given in a review article by Moody.108 The hydroperoxyl radical, which is not so effective an oxidant as the hydroxyl radical, does not attack aliphatic alcohols accordingly, a substantial yield (about 50%) of the aldose is obtained from the higher aldonic acid. In the presence of an excess of hydrogen peroxide, however, the accumulation of ferrous ions in solution catalyzes the production of hydroxyl radicals and lowers the yield of aldose [see Eq. (36)]. 

At The American University, Isbell s major interest in research turned to the study of the oxidation of saccharides with hydrogen peroxide. In collaboration with Dr. Frush, he published some forty papers on the subject. A number of major discoveries were made, including that of a stepwise degradative peroxidation, which is catalyzed by base or by such metals as iron(II). It starts at the anomeric carbon of an aldose, either in the acyclic or the cyclic form, and affords the lower aldose and formic acid (see Fig. 8). Two mechanisms were recognized an ionic one prevalent in strong alkali, and a free-radical process catalyzed by Fe(II) (see Fig. 9). 

Starting from a salt of an aldonic acid, the Ruff oxidative degradation reaction1 leads to an aldose with loss of one carbon atom. Known since 1898, the original process used aqueous hydrogen peroxide as oxidant, in the presence of catalytic amounts of ferric salts. 

At American University, Harriet Frush and Horace Isbell worked on the mechanism of oxidation of carbohydrates by peroxides. They discovered that, in aqueous alkaline hydrogen peroxide, aldoses are quantitatively degraded to formic acid, so that hexoses produce six moles of this acid and pentoses produce five moles. A detailed study of the mechanism of the reaction revealed that degradation takes place by several pathways, the most rapid one involving the formation of peroxy radicals and hydroxy radicals. Thus, when a hydroperoxide-aldose adduct reacts with hydrogen peroxide, a peroxy radical is formed, which decomposes to a hydroxy radical, formic acid, and the next lower aldose. It was also found that, under basic conditions, hydroxy radicals oxidize alditols and aldonic acids to carbonyl compounds in much the same way they do with Fe2+ in the Fenton reaction. During the years she spent at American University, Dr. Frush was able to publish 10 papers without help from any research assistant or laboratory technician. This brought her total to more than 70 papers. 

The polyhydric alcohols, ranging from glycerol to the hexitols (XVII), can also be oxidized, the products including both aldoses and ketoses. As the reaction mixtures are generally resolved as the phenylosazones, only a limited distinction between the products results. In the case of glycerol, n,L-glyceric acid and degradation products are also formed. 

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