Aldonolactones reduction

Addition of lithiated heterocycles to aldonolactones yields carbon-linked nucleosides (56). Thus, the reaction of 2,3 5,6-di-O-isopropylidene-L-gu-lono-1,4-lactone (9b) or 2,3-O-isopropylidene-D-ribono-l,4-lactone (16a) with various lithiated heterocycles gave gulofuranosyl derivatives 53a-g or ribofuranosyl derivatives 54b,c. Gulonolactols 53a-g and ribonolactols 54b,c were acetylated with acetic anhydride in pyridine to yield their acetyl derivatives. The stereochemistry of compounds 53a-g and 54b,c was discussed in terms of the Cotton effect of circular-dichroism curves of the ring-opened alcohols formed upon reduction by sodium borohydride. The configuration at C-l of 53g was proved by means of X-ray analysis (57,58). 

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

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

Reduction of aldonolactones and their derivatives with isotopically modified reducing agents leads to sugars labeled at the anomeric center. Glycosides substituted with deuterium or labeled with tritium are widely employed for kinetic isotope-effect measurements, mechanistic studies, isotope-tracing experiments, and so on. 

Deoxy- and dideoxy-aldonolactones have also been prepared via the bromo derivatives, which on hydrogenolysis yield the corresponding deoxyaldonolactones.293 3-Deoxyaldonolactones have been obtained via /1-elimination reactions on aldonolactones and catalytic hydrogenation of the intermediate 2-enonolactone derivatives.37 The synthetic potential of this reaction was used for the synthesis of 3-deoxyaldonolactones by combining the base-catalyzed elimination of peracylated lactones with the in situ reduction.294... 

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. 

A similar approach to branched-chain aldonolactone sugars has been recently reported by Mattay." Lithium aluminum hydride reduction of photoproduct (36) afforded the desired alcohol which rearranged under acidic conditions to the deoxygenated apiose derivative (38). This process is notable since such reductions usually proceed with cleavage of the oxetane moiety. Also noteworthy are the rapid assemblage of highly oxygenated functionality and the ease of the synthetic procedure. 

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-... 

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 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]. 

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