Aldonic acids, formation

In addition to the aldonic acid formation a minor fraction of the monosaccharides is converted to sugar sulfonic acids. 

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 ... 

Lactonic disaccharides (such as lactobiono-1,5-lactone) reacted with long-chain primary amines to yield model glycolipids of a new type (111,112). For the formation of JV-substituted aldonamides from aldonic acids and amines, A-V -dicylohexylcarbodiimide was employed as the condensing agent. However, no catalyst was needed in the case of the lactones. 

The question then arises if a regioselective opening of a 2,3-rraMS-epoxy carboxamide derived from aldonic acids would occur. The 2,5-di-O-tosyl-D-ribono-1,4-lactone (62) (Scheme 13) was used to find an answer to this question. If treated with ammonia, the 2,5-diamino-2,5-dideoxy-D-ribono-1,5-lactam (63) was obtained as the only product [79]. The NMR spectra of the reaction mixture showed the formation of the diepoxy amide A which was opened at C-5 by ammonia. In this case no internal lactamization could occur, due to the trans 2,3-epoxy group in B (Scheme 13). Thus, a regioselective opening of an acyclic 2,3-epoxy carboxamide took place at C-2. The reaction was complete within 6 days. 

Pfannemtiller et al. showed that it is possible to obtain carbohydrate-containing amphiphiles with various alkyl chains via amide bond formation. For this, mal-tooligosaccharides were oxidized to the corresponding aldonic acid lactones, which could subsequently be coupled to alkylamines [128-136]. Such sugar-based surfactants are important industrial products with applications in cosmetics, medical applications etc. [137-139]. The authors were also able to extend the attached mal-tooligosaccharides by enzymatic polymerization using potato phosphorylase, which resulted in products with very interesting solution properties [140, 141]. 

Brigl and coworkers9 discovered the first example showing that the formation of aldose amides is not restricted to the degradation of acylated nitriles of aldonic acids. By ammonolysis of 2,3,4,5,6-penta-O-benzoyl-aldehydo-n-glucose (16), they obtained l,l-bis(benz-amido)-l-deoxy-D-glucitol (17). 

So far only a table of the 13C chemical shifts of aldonic acid salts and aldonolactones has been published in the literature (Table 5.20, [696]). The carbons of the carboxylate ion groups of all D-aldonic acid salts resonate at 180 + 0.7 ppm. Upon /-lactone formation an upfield shift for C-l and a downfield shift for the /-carbon is observed throughout. 

Several mechanisms have been proposed for the cleavage reactions. One involves formation of an osone from the 1,2-enediol, followed by oxidation to a 2-keto-aldonic acid, which in turn gives the next lower... 

The rates of hydrolysis of the lactones depend on the parent structure for instance, the 1,4-lactone of D-mannonic acid is more stable than that of D-gluconic acid, and the 1,4-lactones of 2-deoxyaldonic acids are more stable than the corresponding aldonolactones. The final attainment of equilibrium between free aldonic acids and their lactones is reached only after many days at room temperature it is, however, accelerated by the presence of strong acids and by heating. A detailed discussion of the formation and hydrolysis of aldonolactones is available in a review by Shafizadeh,59 and the conformations and stabilities of aldonolactones have been discussed by Lemieux.60 Detailed analyses of D-glucono-1,5-lactone and other lactones have been reported.61 13C NMR spectroscopy proved to be a convenient method for monitoring the equilibria.62... 

The equilibrium proportions of the constituents vary with temperature, concentration, and solvent, and are characteristic of each individual aldonic acid. Dehydration in vacuo, or by evaporation from suitable solvents, promotes lactone formation. By suitable choice of conditions, many aldonic acids and both types of lactones have been obtained crystalline 1 considerations have been detailed by Isbell and Frush.63... 

This section deals with acids, that are formally modified aldonic acids, such as keto, deoxy, and branched-chain acids (including the so-called saccharinic acids). The aminoaldonic acids, which are oxidation products of amino sugars, and, in particular, the important nonulosaminic acids (neuraminic acids) and muramic acid, are not discussed here. The formation of saccharinic acids by the treatment of sugars with alkali, and the mechanisms involved, are likewise outside the scope of this chapter. 

Kinetics of oxidation of four pentoses by bromamide-T were conducted in alkaline medium at different temperatures and the overall activation parameters have been calculated.52 Aldonic acids were the oxidation products, and a mechanism was suggested in which formation of the enediol anion of the sugar is the rate-limiting step. As aldoses may undergo epimerization in alkaline solutions, the oxidation of monosaccharides with bromamide-T was also performed in hydrochloric acid solution.53 Kinetic parameters revealed a low reactivity of ketoses relative to aldoses, and indicated that the cyclic forms of the latter are involved in the oxidations. 

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)]. 

In perchloric acid, hexoses and pentoses are oxidized by Ce(IV) via formation of two complex intermediates. The first is partly oxidized following Michaelis-Menten kinetics and partly dissociated to the second, which is oxidized more slowly than the former.180 The first step in the oxidation of aldoses by Tl(III) in the same medium involves the C-l-C-2 cleavage of the aldehydo form of the sugar. Thus, D-glucose gives D-arabinose and formic acid. With an excess of oxidant the final product is carbon dioxide.181 In the presence of a catalytic amount of sulfuric acid in acetic acid, Tl(III) oxidizes maltose and lactose to the corresponding disaccharide aldonic acids. The reaction showed activation enthalpies and enthropies characteristic of second-order reactions.182... 

Certain exceptions to this general scheme have been noted in which the normal hydrogenation of the nitrile group has not taken place. In these cases, a hydrolytic reaction has occurred, with the formation of an aldonic acid instead of the expected aldose.12 The anomalous reaction occurs when the nitrile exists in the (isomeric) iminolactone form for example, compound I is hydrolyzed directly, before hydrogenation can take place. This isomerism of the aldononitriles was established by Papadakis and Cohen,16 and the cyclic structure I was postulated by Wolfrom and coworkers.108... 

Scheme 12 Formation and hydrolysis of FDAM-labeled aldonic acids...

The regioselective functionalisation of aldonolactones is possible at the position a to the lactone and at the primary (co) position. The most efficient method for this functionalisation is treatment of the aldonolactone/aldonic acid with hydrogen bromide in acetic acid (Scheme 1). In this strongly acidic medium the lactone is partly acetylated followed by formation of acetoxonium ions. These then undergo opening with bromide ions to give acetylated bromodeoxyaldonolactones (7). The formation of acetoxonium ions controls the... 

Cyanide ions react with aldehydes and ketones to yield cyanohydrins (Kiliani) (Fig. 2-28). Hydrolysis of the cyanohydrins gives aldonic acids, which can be reduced to aldoses. Kiliani reaction thus opens the possibility for chain lengthening of aldoses. Because of the formation, of a hydroxyl group in place of the aldehyde group a new asymmetric center is generated. It is to be observed, however, that the reaction is subject to so-called asymmetric induction, which means that the diastereoisomers are formed in unequal proportions. 

Fig. 8-18. Oxidative stabilization of cellulose through formation of aldonic acid end groups. R is cellulose chain. After oxidative formation of a glucosone intermediate this undergoes a benzilic acid rearrangement strongly favoring formation of mannonic acid end groups (2). In addition, cleavage of C-1 to C-2 and C-2 to C-3 bonds gives rise to the formation of arabinonic acid (3) and erythronic acid (4) end groups. (In this simplified scheme only the main products are shown.)...

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