Isosaccharinic acids

Depolymerization of starch in alkaline solution proceeds more slowly than in acid and produces isosaccharinic acid derivatives rather than D-glucose as a major product. The mechanism involves a -elimination-type reaction (48). 

Iso-polysaure,/. isopoly acid, -purpurinskure, /. isopurpuric acid. -saccharinsaure, /. isosaccharinic acid, isosmotisch, a. isosmotic. iso-therm, -thermisch, a. isothermal. Iso-therme, /. isotherm, -thlocyanat, -thio-cyanid, n. isothiocyanate, -thiocyansaure, f. isothiocyanic acid, -tonie, /. isotonicity. 

These compounds are O-isopropylidene derivatives of apiose and of a postulated isosaccharinic acid, respectively. 

This mechanism is illustrated in Scheme 4. The reaction occurred in 0.2 M methanolic sodium hydroxide, and the isosaccharinic acid derivatives 78a and 78b obtained constitute the first saccharinic acid nucleosides reported. The configuration of the isomers at the branch-point was established by spectroscopic58 and chemical59 means. 

Lactulose is unstable in alkaline solution, degrading by alkaline peeling and /3-elimination reactions to yield galactose, isosaccharinic acids, and other acid products (Corbett and Kenner 1954). Amines can bring about dehydration and degradation reactions (Hough et al. 1953). Lactulose is similar to sucrose in humectant properties (Huhtanen et al. 1980). 

The five-carbon isosaccharinic acid, 3-deoxy-2-C-(hydroxymethyl)-DL-glycero-tetronic acid, was obtained from alkali-degraded oligo- and polysaccharides containing fi-( —> 4)-linked D-xylose residues.301... 

R. L. Whistler and J. N. BeMiller, 4-Deoxy-3-oxo-D-g7ycero-2-hexulose, the dicarbonyl intermediate in the formation of D-isosaccharinic acids, J. Am. Chem. Soc., 82 (1960) 3705-3707. 

Alberda van Ekenstein rearrangement, followed by the rapid breakdown of this /3-alkoxy carbonyl derivative, probably through an enediol anion (33) into D-galactose (34) and a - and -isosaccharinic acids (35). 

Three structurally isomeric forms have been established for the six-carbon saccharinic acids. In the order of their discovery, these are the sac-charinic or 2-C -methylpentonic acids, the isosaccharinic or 3-deoxy-2-C -(hydroxymethyl)-pentonic acids, and the metasaccharinic or 3-deoxy-hexonic acids. Although none of these six-carbon, deoxyaldonic acids has been crystallized, six are known in the form of crystalline lactones (saccharins). All the possible metasaccharinic acids of less than six-carbon content have been obtained, in the form of crystalline derivatives, by the sugar-alkali reaction. Only one example of a branched-chain deoxyaldonic acid (the racemic, five-carbon isosaccharinic acid) of other than six-carbon content has been so obtained. The formation of saccharinic acids containing more than six carbon atoms remains to be explored. 

This recently discovered, racemic acid of the five-carbon aeries is only the third example of an isosaccharinic acid to be identified as a product of the sugar-alkali reaction. The other examples are the a- and /3-D-isosac-charinic acids of the six-carbon aeries (see pages 48 and 52). 

It should be noted that this assignment of configuration to the 3-deoxypentonic acids, taken in conjunction with the evidence cited in the preceding Section, also confirms the d configuration for the penultimate, secondary carbon atom of a -D-isosaccharinic acid. 

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. 

Lactose is the most convenient source of a -n-isosaccharinic acid and Kiliani s directions based on this disaccharide follow. 

The correctness of structure I for o -D-isosaccharinic acid was eventually confirmed by Kiliani and Matthes when they isolated from the oxidation and decarboxylation, not only the previously obtained meso-di-hydroxyglutaric acid, but also the accompanying, optically active isomer... 

The configuration of C2, the tertiary carbon atom, of o[ -D-isosaccharinic acid has not been established. Unfortunately, application of qualitative rules of configuration based on optical rotation affords disagreeing conclusions in this instance. The positive optical rotation of the phenylhydrazide would indicate the d configuration for C2 on the basis of the phenylhydrazide rule. On the other hand, the reported negative optical rotation of the acid amide would assign the l configuration to this carbon atom on the... 

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 best evidence for the formation of 8 -D-isosaccharinic acid in the sugar-alkali reaction is the recent observation" that treatment of lactose, maltose, or 4-0-methyl-D-glucose with lime-water at room temperature provides initially a mixture of saccharinic acids consisting almost exclusively of a -D-isosaccharinic acid plus an acid with the properties of Nef s /3 -D-isosaccharinic acid [brucine salt, m. p. 185 to 210 (dec.), [a]n - 20 to —22° lactone, [ajp -)-6 to - -8.5°]. An experimental proof that this substance possesses the isosaccharinic acid structure would provide the necessary evidence that it is, indeed, the epimer of a -D-isosaccharinic acid. 

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