Aldoses to aldonic acids

The oxidation of reducing disaccharides (V) leads to the formation of aldobionic acids in a manner similar to the oxidation of aldoses to aldonic acids conditions must be such that the glycosidic linkage is not hydrolyzed. 

Bromine water is an oxidizing agent that oxidizes the aldehyde group to the carboxyl group and aldoses to aldonic acids. 

This method involves the oxidation of aldoses to aldonic acids by potassium hypoiodite in methanol and the condensation of the isolated potassium salt of the aldonic acid in hot acid with o-phenylenediamine (M3). The specific aldobenzimidazole can be identified by the solubility in water, optical rotation in acid, and melting point. This method is not as simple as chromatography. It requires dehydration of the sample and a relatively high concentration of the sugars to be identified. 

A mild oxidant, Tollens reagent converts aldoses to aldonic acids and free silver as follows ... 

There have been reports on the electro-chemical oxidation of glucose to give D-gluconic acid, and its zinc and magnesium salts. The kinetics and mechanism of the Ru04-catalyzed oxidation of aldoses to aldonic acids by alkaline N-bromoacetamide have been smdied, with the conclusion that hypobromite is the reactive oxidizing species. ... 

Aldaric acids may be prepared from aldoses or aldonic acids by oxidation in aqueous solution with oxygen over platinum-charcoal255 or platinum-on-alumina.256 The effect of such promoters as bismuth or gold has also been studied.257 Hydrogen peroxide in the presence of iron salts has been used for the oxidation of uronic acids to aldaric acids.258... 

P. C. C. Smits, B. F. M. Kuster, K. Van der Wiele, and H. S. Van der Baan, The selective oxidation of aldoses and aldonic acids to 2-ketoaldonic acids with lead-modified platinum-on-carbon catalysts, Carbohydr. Res., 153 (1986) 227-235. 

Alkaline hypoiodite oxidizes aldoses, under carefully controlled conditions, almost quantitatively to aldonic acids (see preceding chapter). Measurement of the iodine consumed permits quantitation of the amount of aldose originally present [Eq. (19)]. 

Jeanes and Isbell39 found that, under mild conditions, aldoses are oxidized to aldonic acids, but that nonreducing carbohydrates and ketoses are oxidized only slowly. The rate of oxidation decreases in the order pentoses > hexoses > disaccharides however, in contrast to other oxidants, chlorous acid oxidizes a-hexoses more rapidly than the ft anomers. The yields of aldonic acids are, however, less than those from bromine oxidations.40 The equation for the oxidation in acidic solution was expressed as ... 

Oxidation — The oxidation of aldoses (5.24) with bromine or chlorine in alkaline solution (hypobromites and hypochlorites, respectively) leads to aldonic acids that readily self-esterify (lactonize) into S- (5.25) and y- (5.26) lactones residing with free acid (5.27) in equilibrium. y3-Conformers oxidize more readily than a-conformers. 

Iodine is not reactive in an acidic medium. In a basic medium, it is converted into hypoiodite, a powerful oxidant, and quantitatively oxidizes aldoses into aldonic acids according to reaction (6.2), which is of analytical as well as preparative value. 

This method for the synthesis of higher-carbon ketoses is based on the reaction of diazomethane with an acid chloride to give a diazomethyl ketone which, on hydrolysis (or acetolysis), furnishes a hydroxy (or acetoxy) methyl ketone. The reaction was first applied in the sugar field in 1938 and has since been widely used in the synthesis of ketoses by Wolfrom and coworkers. As developed by Wolfrom, the synthesis uses fully acety-lated derivatives in the following stages aldose — acetylated aldonic acid acetylated aldonyl chloride acetylated diazomethyl ketose — acetylated ketose — ketose. The method is illustrated in the synthesis of D-galacto-heptulose (10). ... 

Both aldoses and ketoses are oxidized to aldonic acids by Tollens reagent (Ag, NH3, HO ), so that reagent cannot be used to distinguish between aldoses and ketoses. Recall from Section 20.3, however, that Tollens reagent oxidizes aldehydes but not ketones. Why, then, are ketoses oxidized by Tollens reagent, while ketones are not Ketoses are oxidized because the reaction is carried out under basic conditions, and in a basic solution, ketoses are converted into aldoses by enolization (Section 19.2). For example, the ketose D-fructose is in equilibrium with its enol. However, the enol of D-fructose is also the enol of D-glucose, as well as the enol of D-maimose. Therefore, when the enol reketonizes, all three carbonyl compounds are formed. 

In the first step of the synthesis (the Kiliani portion), the aldose is treated with sodium cyanide and HCl (Section 18.4). Addition of cyanide ion to the carbonyl group creates a new asymmetric carbon. Consequently, two cyanohydrins that differ only in configuration at C-2 are formed. The configurations of the other asymmetric carbons do not change, because no bond to any of the asymmetric carbons is broken during the course of the reaction (Section 5.12). Kiliani went on to hydrolyze the cyanohydrins to aldonic acids (Section 17.18), and Fischer had previously developed a method to convert aldonic acids to aldoses. This reaction sequence was used for many years, but the method currently employed to convert the cyanohydrins to aldoses was developed by Serianni and Barker in 1979 it is referred to as the modified Kiliani-Fischer synthesis. Serianni and Barker reduced the cyanohydrins to imines, using a partially deactivated palladium (on barium sulfate) catalyst so that the imines would not be further reduced to amines. The imines could then be hydrolyzed to aldoses (Section 18.6). 

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. 

Oxidation of aldoses yields aldonic acids (onic acids), uronic acids, and glycaric acids (sugar dicarboxylic acids, aldaric acids) (Fig. 36). Aldonic acids easily cyclize to the corresponding y-lactones. Glycaric acids may form dilactones. 

Pyridine nucleotide-dependent dehydrogenases (C 2.1) transform aldose derivatives to uronic acids, e.g., UDP-D-glucose to UDP-D-glucuronic acid and in animals also to aldonic acids, e.g., D-glucose-6-phosphate to D-gluconic acid-6-phos-phate (glucose-6-phosphate dehydrogenase). 

Bromine and hypoiodite oxidations are particularly suitable for the preparation of aldonic acids from aldoses. Similarly, uronic acids are converted to saccharic acids. Of less value is the oxidation of primary alcoholic to aldehydic groups. In this manner, glycosides can be converted to uronides and polyols to aldoses and aldonic acids. 

Under mild conditions, e. g., with bromine water in buffered neutral or alkaline media, aldoses are oxidized to aldonic acids. Oxidation involves the lactol group exclusively. 3-Pyranose is oxidized more rapidly than the a-form. Since the P-form is more acidic (cf. 4.2.1.3), it can be considered that the pyranose anion is the reactive form. The oxidation product is the 5-lactone which is in equilibrium with the y-lactone and the free form of aldonic acid. The latter form prevails at pH > 3. 

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. 

We recall dilute nitric acid oxidizes aldoses to aldaric acids. The symmetry properties of the aldaric acid provide information about the possible configurations of the secondary hydroxyl groups. If the aldonic acid formed by oxidation is optically inactive, the hydroxyl groups occur in a symmetrical arrangement. For example, D-galactose gives an optically inactive aldaric acid... 

---