Reduction of Aldonolactones

Reduction of Aldonolactones 1. Reduction to Aldoses and Alditols 

Diisobutylaluminum hydride was also employed (153) for the reduction of 2,6-dideoxy-3-C-methyl-D-arabmo-hexono-1,4-lactone (121) to an antibiotic component, the branched-chain sugar evermicose (2,6-dideoxy-3-C-methyl-D-nrabmo-hexose, 122). The L-enantiomer of 122 (olivomycose, 125a), L-amicetose 125b, and 2,6-dideoxy-3-C-methyl-L-n Zw-hexose (l- 

Polarographic (168) and electrochemical (169) procedures for the reduction of D-ribono-1,4-lactone have been developed, and the latter has been applied on a pilot-plant scale. 

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. 

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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. 

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. 

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 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]. 

The non-catalytic reduction of aldonolactones to the corresponding aldoses and/ or alditols by sodium borohydride or lithium aluminum hydride has also been studied [1]. Because of the stoichiometric character of these procedures they are, however, limited to laboratory use. 

Two new methods for the reduction of aldonolactones to aldoses have been developed for use in small-scale syntheses either the lactone itself was reduced with diborane in THF, or an 0-tetrahydropyranyl derivative was reduced with a 1 1 mixture of lithium aluminium hydride and aluminium chloride in ether. The yield of aldose depends on a number of factors and may be low due to the ease of reduction of the aldose to the alditol. The catalytic hydrogenation of D-glucose in the temperature range 100—170 °C and at pressures of 20—80 atmospheres has been examined the effects of pH and promoters (e.g. magnesium, barium chloride, calcium sulphate) were also examined. The rate of hydrogenation was enhanced at pH 8, and calcium sulphate was the most effective promoter at pH 6.8. 

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. 

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. 

Akin to the aforementioned synthesis is the reaction of 2-lithiopyridines with derivatives of aldonolactone such as 8218, which usually took place stereospecifically to give one of the two possible hemiacetal (lactol) C-nucleosides 839. Reduction of the latter gave a mixture of the two possible stereoisomers 840 (74JOC1374 88CPB634, 88M115) (Scheme 235). 

The aldonolactone derivative 838 also reacted with 5-lithiopyrimidines to give a mixture of the two hemiacetal C-nucleosides 986. Reduction of the latter with sodium borohydride and removal of the protective groups gave the corresponding acyclo analogs 893 (68JOC140) (Scheme 287). 

Deoxy-sugars can be synthesized from aldonolactones via -elimination or bromlnatlon procedures. 3-Deoxy-D-arablno-hexono-1,5-lactone, readily available from D-glucono-1,5-lactone by sequential acetylation, B-eliminatlon, hydrogenation, and deprotection, has been converted to 2-deoxy-D-erythro-pentose In 92)J yield by Indirect electrochemical oxidation. 3-Deoxy-D-arablno-hexose, which exists as a 53 30j 17 mixture o-f the o- and B-pyranose, and a-furanose forms In aqueous solution, has been synthesized by reduction of the 2,U,6-trl-0-benzoyl derivative of... 

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