Saccharinic acids from hexoses

In support of his contention that /3 -D-isosaccharinic acid is present in the hexose-alkali reaction mixture, Nef also cited certain observations of Kiliani and Eisenlohr, who oxidized (with nitric acid) the residue obtained, after substantial removal of a -D-isosaccharinic acid and the meta-saccharinic acids, from the lactose-alkali reaction mixture. Among the products identified was the tribasic acid, (H02C)2C(0H)—CHj—CHOH— CO2H, previously obtained by a similar oxidation of a -D-isosaccharinic acid (see page 50). Nef concluded that the tribasic acid must in this instance have arisen from j3 -D-isosaccharinic acid. This conclusion ignores, however, the experimental demonstration by Kiliani and Eisenlohr that the residue subjected to oxidation had still contained a small proportion of a -D-isosaccharinic acid, isolable as the slightly soluble calcium salt. 

The saccharinic acids formed from hexoses have been especially examined because of the relationships of the a and /8 isomers (C-2 epi-mers). Structures of saccharinic acids derived from D-glucose are glu-cometasaccharinic acid (51), glucoisosaccharinic acid (52), and glucosaccharinic acid (53). The a- and /3- isomers of metasaccharinic acid can reversibly isomerize when exposed to base because of the labile proton at C-2. 

Shortly after the discovery of Peligot s a -D-glucosaccharin, Dubrun-faut reported that the calcium salt of a monobasic acid resulted from the action of lime-water on maltose. Cuisinier named the acid isosaccharinic acid, after he had prepared from it a crystalline lactone (CeHioOt) isomeric with Peligot s a -D-glucosaccharin. The name was expanded to a -D-iso-saccharinic acid after Nef obtained evidence of the concurrent formation of its epimer, /3 -D-isosaccharinic acid, in the hexose-alkali reaction. 

The role of substitution in determining the course of saccharinic acid formation has been critically examined recently by Kenner and coworkers. They conclude that an 0-glycosyl or 0-alkyl anion is more readily extruded from the sugar enediol anion of the Isbell mechanism than is a hydroxyl ion. In addition, substitution at certain positions in the sugar molecule may inhibit competing side-reactions. For example, a substituent at C4 of the hexose molecule inhibits cleavage (by reverse aldolization) into two three-carbon fragments and the resultant formation of lactic acid, a result that had been demonstrated earlier by the experiments of Evans and his associates. A combination of the two above effects, then, preferentially... 

As would be expected from the above considerations, substitution at C6 of a hexose has, at most, only a minor effect on the course of saccha-rinic acid formation. Thus, 6-0-(a-D-galactosyl)-D-glucose (melibiose) plus lime-water gives lactic acid and a mixture of the corresponding metasac-charinic, isosaccharinic, and saccharinic acids.The qualitative experiments with melibiose and with 6-0-methyl-D-glucose, based mainly on paper chromatography, suggest that the metasaccharinic acids may be the principal products from hexoses substituted at C6. 

In contrast to the above formation of metasaccharinic acid, fragment recombination appears to be a predominant feature in the formation of the branched-chain a -D-glucosaccharinic acid from D-mannose-l-C plus lime-water. In this case, the radioactivity originally present in Cl of the hexose was found to have become distributed almost entirely between the methyl carbon atom and the tertiary carbon atom of the saccharinic acid, with the latter atom more heavily labeled than the former. In contrast to these observations, the Isbell mechanism, in the absence of compli-... 

The saccharinic acids formed from some of the pentoses and hexoses have been the objects of study by Nef and his students. Glattfeld and Hanke reported in 1918 that, during the oxidation of maltose in alkaline solution, an acid had been produced whose phenylhydrazide had an analysis agreeing perfectly with that calculated for a four-carbon saccharinic acid. Furthermore, the properties of the free aeid were those which would be expected of one of these acids. Its configuration could not, however, be reported at that time because of the absence of data as to the properties and constants of the four-carbon saccharinic acids. Nef had also referred to the handicap which this lack of information had imposed on the work with sugars in alkaline solution. Consequently, with this in mind, Glattfeld began in 1920 the systematic synthesis of the four-carbon saccharinic acids. 

A wide range of carbohydrates is degraded by acids to furan compounds. For example, pentoses give 2-furaldehyde, and hexoses, 5-(hydroxymethyl)-2-furaldehyde (58), which may react further to yield levulinic acid. In 1910, Nef suggested the first mechanism, (55) to (58), for the formation of 5-(hydroxymethyl)-2-furaldehyde. His proposal was made at the end of his classical paper on the saccharinic acids, and was overlooked by subsequent workers and reviewers. In 1944, Haworth and Jones advanced an identical mechanism for the formation of 5-(hydroxymethyl)-2-furaldehyde from D-fructose. 

Dehydration is one of the important acid-base-catalyzed reactions of carbohydrates. In alkaline media, a deoxyaldosulose is formed from a carbohydrate molecule after one molecule of water has been split oflF this product then usually undergoes an intramolecular, oxidoreductive disproportionation to give the corresponding saccharinic acid in acidic media (with pentoses and hexoses), up to three molecules of water are split oE per molecule, with formation of 2-furaldehyde or 5-(hydroxymethyl )-2-furaldehyde. In many cases, polarography makes possible the monitoring of carbohydrate dehydration and the determination of its final products. 

Lactic acid occurs amongst the products of the action of alkali on hexoses. From 1 mole of D-glucose, treated at 25°C. with benzyltrimethylammonium hydroxide, Evans reported the production of 1.2 moles of racemic lactic acid (60 % of a theory of 2 moles per mole hexose). The substance apparently can be obtained by the action of alkali on any sugar (inclusive of trioses, pentoses, disaccharides, etc.) (99). Its preparation from sucrose under conditions of high temperature and pressure has been extensively studied from the viewpoint of potential industrial application. Lactic acid may be considered as the saccharinic acid (see below) related to glyceraldehyde and may arise from the rearrangement of a triose fragment. 

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