Aldonic acids, preparation

Aldonic Acid Preparation and Subsequent Dehydration to Give an Aldonolactone... 

Derivatives of aldoses in which the terminal aldehyde function is oxidized to a car boxylic acid are called aldonic acids Aldonic acids are named by replacing the ose ending of the aldose by omc acid Oxidation of aldoses with bromine is the most com monly used method for the preparation of aldonic acids and involves the furanose or pyranose form of the carbohydrate... 

When a preparative method for an aldonic acid is re quired bromine oxidation is used The aldonic acid is formed as its lactone More properly described as a reaction of the anomeric hy droxyl group than of a free aldehyde... 

Other multifunctional hydroxycarboxylic acids are mevalonic and aldonic acids which can be prepared for specialized uses as aldol reaction products (mevalonic acid [150-97-0] (13)) and mild oxidation of aldoses (aldonic acids). 

Although the Tollens reaction is a useful test for reducing sugars, it doesn t give good yields of aldonic acid products because the alkaline conditions cause decomposition of the carbohydrate. For preparative purposes, a buffered solution of aqueous Br2 is a better oxidant. The reaction is specific for aldoses ketoses are not oxidized by aqueous Br2. 

Other reagents have been used as adjuncts for the Pudovik addition as well. Particularly to be noted are the uses of basic alumina289 and potassium fluoride.290 292 The latter has provided an excellent route for the preparation of a phosphonate directly related to an aldonic acid (Equation 3.18).290... 

Fischer s involvement with the relative configurations of the sugars required the preparation of pure substances and he gradually accumulated experimental data (20-22), which required the formation of epimeric aldonic acids in unequal amounts (see Table I). Thus, he was able to write (23) in 1892 ... 

The bromodeoxyaldonolactones have been used for the preparation of aminodeoxy aldonic acids and aminodeoxy sugars via azido derivatives (45,46). Likewise, a- and /J-aminopolyhydroxy acids have been prepared by treatment of the bromodeoxyaldonolactones with liquid ammonia (47). Thus, 3-amino-3-deoxy-D-threonic acid and 3-amino-3-deoxy-D-arabin-onic acid (40b) were obtained from 2-bromo-2-deoxy-L-threono- or D-xy-lono-1,4-lactone (38). It was shown that 2,3-epoxy carboxamides (namely, 39) are intermediates of the reaction. Heating at 90° for long periods led to the 3-amino-3-deoxyaldonamides, which upon acid hydrolysis yielded the corresponding aldonic acids. 

Aldonamides are readily prepared by reaction of lactones with liquid ammonia (86,99,100), with ammonium hydroxide (101,102), or by bubbling ammonia gas into alcoholic solutions of the sugar lactones (103-104). Aldonamides of the tetronic adds are stable in aqueous solution (105), but penton- or hexon-amides are hydrolyzed, as shown by the change of the optical rotation of the amide solutions (106). The hydrolysis is catalyzed by acids and bases, and the product was the ammonium salt of the aldonic acid. 

Similarly, open chain C-nucleosides of adenine have been prepared by condensing 4,5,6-triaminopyrimidine with aldonic acids (or aldonolac-tones) of various chain-lengths. The amides (102) first formed were thermally cyclized, affording the 8-(hydroxyalkyl)adenines (103) in rather low yields (119). 

We have devised a very simple procedure for the preparative synthesis of various aldonic acids from the corresponding aldoses. This green chemistry process takes advantage of the availability of cheap, robust industrial enzymes. 

K. Bock, I. Lundt, and C. Pedersen, Reaction of aldonic acids with hydrogen bromide. I. Preparation of some bromodeoxyaldonic acids, Carbohydr. Res., 68 (1979) 313-319. 

G. Limberg, I. Lundt, and J. Zavilla, Deoxyiminoalditols from aldonic acids. VI. Preparation of the four stereoisomeric 4-amino-3-hydroxypyrrolidines from bromodeoxytetronic acids. Discovery of a new a-mannosidase inhibitor, Synthesis (1999) 178-183. 

The first step in the degradation is the preparation, starting from an aldose, of the acylated nitrile of an aldonic acid. The nitrile and the acyl groups may be removed by various methods to yield a new aldose,... 

Wohl prepared the acylated nitriles of the aldonic acids by heating the aldose oximes with a mixture of sodium acetate and acetic anhydride. With careful control of the reaction, this method may be used for preparative work with fairly good results. 

Afterward, Behrend found that the nitrile is also produced when o-glucose oxime is treated with pyridine and acetic anhydride, and this method has been extended to the preparation of other nitriles of aldonic acids. ... 

The first benzoylated nitrile of an aldonic acid was prepared by Brigl, Muhlschlegel and Schinle by benzoylation of the n-manno-n- oZa-heptononitrile the hexabenzoyl derivative was obtained. A series of benzoylated nitriles has recently been prepared by Restelli de Labriola and Deulofeu by treatment of the oximes of L-rhamnose, D-glucose, D-galactose and D-mannose with benzoyl chloride and pyridine. They were the sole products and were obtained in high yields. 

Free aldonic acid nitriles have been prepared in a few cases. Kiliani obtained the cyanohydrin of D-fructose by adding hydrocyanic acid to the ketose and Miksic obtained the nitriles already mentioned in a similar way. 

The nitrile group is very sensitive to alkalis and the elimination of it by the action of potassium hydroxide on acetaldehyde cyanohydrin was described by Simpson and Gauthier as one of the reactions of the acetaldehyde cyanohydrin, a substance that they prepared for the first time. That the nitriles of the aldonic acids yield cyanides under the action of alkali, is described by Wohl as one of the properties of penta-acetyl-D-glucononitrile. 

Among the classic methods for the extension of the aldose chain by one carbon atom from the reducing end [9J, the Kiliani-Fischer cyanohydrin synthesis [10] is a milestone in carbohydrate chemistry. However after 110 years from discovery and numerous applications [11], including the preparation of carbon and hydrogen isotopically labeled compounds for mechanistic and structural studies [12], there are still several drawbacks that make the method impractical. These are the low and variable degree of selectivity and the harsh reaction conditions that are required to reveal the aldose from either the aldonic acid or directly from the cyanohydrin. Synthetic applications that have appeared in recent times confirmed these limitations. For instance, a quite low selectivity was registered [13] in the addition of the cyanide ion to the D-ga/acfo-hexodialdo-l,5-pyranose derivative 1... 

H. Kiliani, as Fischer always emphatically acknowledged, discovered and developed the method of building up the aldose series by the cyanohydrin reaction to give nitriles from the nitrile, the next higher aldonic acid could then be prepared. In 1890, A. Wohl, working in Fischer s Berlin laboratory, elaborated the dehydration of an aldose oxime to the nitrile, from which the next lower aldose could be prepared by loss of hydrocyanic acid. Fischer exploited the possibilities of sugar extension and degradation afforded by the use of these two important methods. 

L-erythronic acids, respectively, and D-xylose to D-threonic acid.44 Isbell et al. elucidated the mechanism of this process45 (see the following Chapter). Degradation to a lower aldonic acid can be achieved by oxidation of an unsaturated sugar derivative. The method of Reichstein et al.46 for the preparation of L-threono-1,4-lactone by permanganate oxidation of 5,6-0-isopropylidene-L-ascorbic acid was improved by Perel and Dayton to afford the crystalline lactone in 65% yield.47... 

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