Aldonic acids and lactones

Carbohydrate Chemistry, Volume 30 The Royal Society of Chemistry, 1998 

Syntheses of some pentonohydroxamic acid derivatives are covered in Chapter 10. Alkaline degradation of 5-O-a-D-glucopyranosyl-D-fructopyranose (leucrose) has afforded two novel saccharinic acids, 2-C-(2-hydroxyethyl)eiy-thronic acid and 2-C-(2-hydroxyethyl)threonic acid. Treatment of 4,6-O-ethyl-idene-D-glucose with the sulfur ylid JNr,iST-diethyl trimethylsulfonium-acetamide gave the epoxyaldonamide 6 as well as stereoisomers.  

Chemically defined glycolipids have been prepared by aminolysis of lacto-biono-1,5-lactone and coupling of the products with long-chain dialkyl-L-gluta-mates.  

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Dicarbonyl sugars glycos-S-uloses - Aldonic acids and lactones... 

The halogens and their oxyacids probably are the most important oxidants used in the carbohydrate field. They are widely used as bleaching agents, but the mechanism of this action remains to be clarified. As reagents for preparatory purposes (particularly for aldonic acids and lactones) and for analytical procedures, they are very important. Periodic acid, discussed in a later section, has an important application for the elucidation of structures of carbohydrates. A number of valuable commercial products are made by treatment of polysaccharides with halogens, particularly chlorine or hypochlorous acid, but the nature of these actions, such as the modification of starch, has not been clarified. 

Oxidation to Sugar Acids and Lactones. When the aldehyde group of an aldose is oxidized, the resulting compound is an aldonic acid (salt form = aldonate) (11)4. Some aldonic acids are products of carbohydrate metaboHsm. 

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. 

Aldono-1,5-lactones and free aldonic acids react with alcohols in the presence of hydrogen chloride to give the corresponding alkyl aldonates (84). The reaction is slower with 1,4-lactones. Because esterification takes place very slowly in the absence of an acidic catalyst, aldonic acids and their lactones may be recrystallized from boiling alcohols without appreciable esterification (85). However, in some instances, alkyl esters are formed under these conditions. For example, essentially pure ethyl L-mannonate was isolated (6.4% yield) from the mother liquors of crystallization L-man-nono-1,4-lactone, obtained by Kiliani synthesis from L-arabinose (86). Similarly, repeated recrystallization from ethanol of crude 2,3,4,6-tetra-O-acetyl-D-glucono- 1,5-lactone afforded the corresponding ethyl gluconate derivative (87). 

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. 

In the carbohydrate series, the acids encountered are aldonic, aldaric, uronic, or saccharinic acids. Often, these acids are readily transformed into their lactones or methyl esters, and it is as derivatives of these that they are commonly studied. Table VIII (see p. 136) records examples in which derivatives of such acids and lactones have been subjected to gas-liquid chromatography. 

All the aldonic acids and their lactones obtained on oxidation of the aldohexoses are optically active. The presence of a carboxyl group at one end of the carbon chain and a CH2OH at the other precludes the existence of meso forms. 

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... 

Under dehydrating conditions, it is probable that, in addition to lactonization, intermolecular esterification also occurs, yielding esters of aldonic acids and polymers. 

The carbonyl frequency in the infrared spectrum provides a fairly characteristic method for differentiating between 1,4- and 1,5-lactones of aldonic acids. With few exceptions, the absorptions are in the range 1790-1765 and 1760 to 1725 cm-1, respectively.69 Configurational and conformational conclusions have been drawn from H and 13C NMR spectroscopy of aldonic acids and aldonolactones, using different correlation methods, enriched compounds, and shift reagents. For example, the solution conformation of aldono-1,4-lactones enriched with 13C at C-l have been determined on the basis of the coupling constants (homo and heteronuclear). In general, 0-2 is oriented quasi-equatorially due to stereoelectronic factors.36 Similar conclusions were made by Horton and Walaszek, who described the conformation of pentono- 1,4-lactones as an equilibrium between the 3E and forms.70 Conformations of D-hexono-1,4-lactones in solution have also been studied by NMR spectroscopy.70a The solution equilibrium of protected derivatives and their conformations have been described.71... 

Optical rotatory dispersion studies on lactones of aldonic acids and other carbohydrate acids were made by Hirst et al.11 and later by Okuda et al.7S The latter workers related the absolute configuration at C-2 of aldono-1,4-lactones to the sign of the Cotton effect. 

Esters are prepared by reaction of aldonic acids or lactones with an alcohol in the presence of hydrogen chloride 80 the reaction is slower with 1,4-lactones. Amides are readily formed from lactones by reaction with liquid ammonia followed by evaporation of the solvent.81 D-Gluconamide has also been prepared by treatment of D-glucono-1,5-lactone with concentrated ammonium hydroxide and subsequent precipitation with ethanol.82 A-Substituted aldonamides may be obtained by reaction of the aldono-lactones with ethanolamine, diethanolamine, and related species.83... 

Chloric acid, in conjunction with catalysts (particularly vanadium pentaoxide), is used for the oxidation of aldonic acids or lactones to the 2-glyculosonic acids. Thus, D-glucono-1,4-lactone (9) and potassium D-galactonate in methanol, in the presence of phosphoric acid and vanadium pentaoxide, are oxidized by chloric acid to methyl D-arabino-2-hexulosonate (10) and methyl D-/yxo-2-hexulosonate, respectively.38 At moderate temperatures in the absence of a catalyst, aldoses, ketoses, and sucrose are inert to the action of chlorates over a several weeks time period 39 bromates in alkaline solution also exert no oxidative action (Scheme 5). 

The procedure of Moore and Link16 is now generally preferred for the preparation of benzimidazoles from aldonic acids, their lactones, or their salts. Their specific example starting with calcium D-gluconate is given below. 

Although lactones may be reduced electrochemically or via Bouveault-Blanc reactions to produce diols, such reactions are more frequently used to prepare lactols. Both cathodic (Hg or Pb) and Na/Hg reduction are useful in the preparation of alditols from aldonic acid y-lactones. The reductions may be easily stopped at the intermediate aldose stage. ... 

The oxidation products of L-rhamnose treated with an excess of bromine for five days included a small amount of 5-keto-L-rhamnonic lactone 1000 g. of L-rhamnose gave 550 g. of L-rhamnonic lactone and 55 g. of the keto derivative. In confirmation, Voto6ek and Malachata achieved the partial conversion of L-rhamnonic lactone to the keto derivative. The very low yield, however, is indicative of the slowness of the reaction and the relative stability of the normal aldonic acids or lactones toward further oxidation. 

In the presence of a tertiary amine, in particular pyridine (Sec. 31.6), an equilibrium is established between an aldonic acid and its epimer. This reaction is the basis of the best method for converting an aldose into its epimer, since the only configuration affected is that at C-2. The aldose is oxidized by bromine water to the aldonic acid, which is then treated with pyridine. From the equilibrium mixture thus formed, the epimeric aldonic acid is separated, and reduced (in the form of its lactone) to the epimeric aldose. See, for example, Fig. 34.4. 

Acids and Lactones - made by mild oxidation of an aldose, for example, to form an aldonic acid (see here). Free aldonic acids are in equilibrium with lactones (see here). In metabolic pathways, oxidation at carbon 6 of glucose yields glucuronic acid. 

Other articles " dealt with the preparation of aldonic acids, their lactones, and the basic calcium salts of aldonic acids obtained by electro-oxidation. By the procedure proposed, not only calcium, but also... 

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