Aldoses aldonolactones

The results of inhibition studies with aldonolactones and 5-amino-5-deoxyaldonolactams may be summarized as follows y -D-glycosidases are inhibited by 1,5-lactones and the lactams some 100- to > 10,000-fold better than by the parent aldoses, with Kj values from 200 //Mto <0.1 nM. Al-dono-1,4-lactones are probably no better inhibitors than aldoses or polyols of comparable structure, with the possible exception s of 2-acetamido-2-deoxy-D-glucono-1,4-lactone. 

VIII. Reduction of Aldonolactones 1. Reduction to Aldoses and Alditols... 

Isotopic Labeling and Substitution at the Anomeric Center of Aldoses by Reduction of Aldonolactones... 

Aldonolactones are commercially available at low cost, when compared to most of the common monosaccharides. They are typically synthesized by selective anomeric oxidation of unprotected aldoses with bromine [6]. Usually the thermodynamically more stable five-membered lactone (y-lactone) predominates over the six-membered form, with the exception of o-gluconolactone, which crystallizes as the 1,5-pyranolactone (5-lactone) [7] (Scheme 1). Another method for the preparation of sugar lactones is the dehydrogenation of unprotected or partially... 

He himself found that aldonolactones could be reduced with sodium amalgam to the aldoses. Thus, the way was opened to proceed from any pentose to the next higher aldose, which, as he soon showed, always arose in two stereoisomeric forms because of the introduction of a new asymmetric center. Another novel method created was the epimerization of aldonic... 

Oxidation of aldoses by hypoiodite can also be used for preparative purposes.7 Other types of halogen oxidants, especially A-halo compounds, are useful. For example, A -bromocarbamide was recommended by Kiss8 as a selective and convenient reagent for oxidizing benzylated sugars to their corresponding aldonolactones in yields exceeding 90%. Another example is the use of A-iodosuccinimide and tetrabutylammonium iodide.9... 

N. Sperber, H. E. Zaugg, and W. M. Sandstrom, The controlled sodium amalgam reduction of aldonolactones and their esters to aldoses and an improved synthesis of D-arabinose, J. Am. Chem. Soc., 69 (1947) 915-920 and references cited therein. 

Many other cations of transition metals have been employed for the oxidation of sugars. For example, the oxidation of aldoses by hexachloroiridate(IV)183,184 and tetrachloroaurate(III)183,185 in hydrochloric acid led to the corresponding aldonic acids or aldonolactones. The observed... 

V. M. Parikh and J. K. N. Jones, Oxidation of sugars with ruthenium dioxide-sodium periodate a simple method for the preparation of substituted keto sugars, Can. J. Chem., 43 (1965) 3452-3453 compare R. H. Hall and K. Bischofberger, The preparation of aldonolactones and lactols by oxidation of aldoses with ruthenium(VIII) oxide, Carbohydr. Res., 65 (1978) 139-143. 

There is no generally useful nonhydride method for the direct reduction of carboxylic acid esters to aldehydes. There are, however, procedures which are valuable under particular circumstances. An important example is the one-electron reduction of aldonolactones to aldoses. Two factors presumably contribute to the success of these reactions firstly the presence of electron-withdrawing substituents in the substrates, raising the reactivity of the carbonyl group, and secondly the ability of the products to form cyclic hemiacetals stable to further reduction. 

The use of sodium amalgam originates with E. Fischer. The method was a cornerstone of his aldose homologation (cyanohydrin formation, hydrolysis, lactone formation and reduction) which was so important to the development of carbohydrate chemistry. Although the yields obtained by Fischer were moderate ca. 20-50%), more recent work by Sperber et al. has resulted in significant improvements. In particular, they discovered that control of the pH of the reaction mixture was very important. At pH 3-3.5, yields in the range 52-82% were obtained with a variety of aldonolactones. As an example, the preparation of arabinose is shown in equation (4). If the pH was allowed to rise, yields were lower due to overreduction. Methyl esters of aldonic acids could also be used as substrates. 

Early work showed that the reduction of aldonolactones to aldoses may also be carried out by catalytic hydrogenation over Pt02 in aqueous solution.4 Using this method, o-glucono-1,5-lactone was reduced to glucose in up to 80% yield, the remainder of the product being o-gluconic acid. However, careful optimi-... 

The anomeric forms derived from equilibration of aldoses give rise to multiple peaks when trimethylsilylated and gas chromatographed [311]. A method of overcoming this problem, assuming that mutarotation itself is not under study, is to modify the aldose. It can be oxidised and lactonised to the aldonolactone, for example, and characterised as its TMS derivative [322]. Alternatively for the identification of aldoses and alditols, more use may be made in the future of the separations achievable on open tubular columns of the poly-0-acetylaldonic nitriles (18) produced from aldoses and the poly-acetyl esters from alditols [323]. Figure 1.18 shows the separation of 32 assorted polyols and aldoses. 

Esters of fatty acids are only to some extent reduced to the alcohols by sodium amalgam. Aldonolactones and their esters, however, are reduced to aldoses by Na(Hg) [99]. Optimal conditions are found at pH 3-3.5 and temperatures below 15°C 2.5-3 atoms of Na [as 2.5% Na(Hg)] are used per mole of lactone. Yields of different aldoses range from 50 to 84% [100,101]. 

In this chapter, methods for oxidation, reduction, and deoxygenation of carbohydrates are presented. In most cases, the reactions have been used on aldoses and their derivatives including glycosides, uronic acids, glycals, and other unsaturated monosaccharides. A number of reactions have also been applied to aldonolactones. The methods include both chemical and enzymatic procedures and some of these can be applied for regioselective transformation of unprotected or partially protected carbohydrates. 

Unprotected aldoses can be selectively oxidized at the anomeric center to afford aldonic acids/aldonolactones. This oxidation can be achieved by chemical as well as by biochemical... 

Unprotected aldoses and ketoses can be reduced to afford alditols while aldonolactones can be reduced to give either aldoses or alditols. The reagent of choice for reduction to alditols is sodium borohydride since it is both cheap and convenient to use. The reduction is carried out under mild conditions at room temperature in an aqueous solution. Sodium borohydride is stable in water at pH 14 while it reacts with the solvent at neutral or slightly acidic pH, but at a slower rate than the rate of carbonyl reduction. In some cases, the product will form esters with the generated boric acid. These borate complexes can be decomposed by treatment with hydrochloric acid or a strongly acidic ion-exchange resin and the boric acid can be removed in the work-up as the low boiling trimethyl borate by repeated co-evaporation with methanol at acidic pH [155]. 

The reduction of aldoses/ketoses occurs readily with sodium borohydride and during the reaction the pH increases to about 9 (O Scheme 19) [155]. For the reduction of aldonolactones in water the first step of the reduction has to be carried out at a pH around 5 in order to avoid ring-opening of the lactone to the corresponding sodium salt which will not react with sodium borohydride. The pH control can be achieved by performing the reduction in the presence of an acidic ion-exchange resin, e. g., Amberlite IR-120 [156]. In this way, it is possible to stop the reduction at the aldose step. Alternatively, more sodium borohydride can be added and thereby increasing the pH to 9 by which the alditol is obtained (O Scheme 19). The reduction of aldonolactones to alditols can also be performed in anhydrous methanol or ethanol where hydrolysis of the lactone is not a side reaction [156]. 

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