Parasaccharinic acid

Deoxy-D-l2/a o-hexonic acid ( /3 -D-galactometasaccharinic acid) was discovered by Kiliani and Sanda as a minor product of the n-galactose-al-kali reaction. Kiliani believed that this product was a new type of branched-chain saccharinic acid, and referred to it throughout subsequent publications as parasaccharinic acid. The evidence, provided both by his own work and that of Nef, that Kiliani s parasaccharinic acid contained, in fact, the epimer of a -D-galactometasaccharinic acid, is outlined on page 56. 

S) fi"-D-Galactometasaccharinic Acid.—Kiliani and Sanda reduced their parasaccharinic acid in the usual manner with hydriodic acid and red phosphorus. The product was a hexanoic lactone whose boiling point (217.5°) was precisely intermediate between that (220°) of the n-hexanoic 1,4-lactone obtained by a similar reduction of a -D-galactometasaccharinic acid and that (215°) reported for 2-ethylbutyro-l, 4-lactone. Kiliani, however, chose the latter structure for his lactone, since the corresponding acid, like DL-(2-ethyl-4-hydroxybutyric acid) and unlike either the enantiomor-... 

At this stage, the possible presence of a branched-chain saccharinic acid in Kiliani s preparation was supported only by (a) the properties of the barium salt of the hydroxyhexanoic acid obtained from it on reduction and (b) the reported oxidation of parasaccharinic acid with nitric acid to a tribasic acid. The latter evidence was retracted by Kiliani in his final report on the matter, when he stated that the previous identification of hydroxycitric acid was in error and that this tribasic acid is, in fact, ( — )-tartaric acid. In addition, he now observed that oxidation of parasaccharinic acid with nitric acid, followed by reduction with hydriodic acid and red phosphorus, gives a low yield of adipic acid. 

The hypothesis of the existence of the branched-chain parasaccharinic acid now depended solely on the identity of the reduction product, hydroxyhexanoic acid. To support his previous contention that the barium salt of this acid is, indeed, barium 2-ethyl-4-hydroxybutyrate, Kiliani also prepared the calcium salt and found that it, too, closely resembled the corresponding salt of 2-ethyl-4-hydroxybutyric acid. As emphasized by Kiliani, neither the reductions with hydriodic acid and red phosphorus nor the oxidations with nitric acid proceed in good yield to single products. Accordingly, Kihani remained firm in his conviction that his preparation, although it was apparently a mixture, nevertheless contained the branched-... 

Nef s theory of the mechanism of formation of the saccharinic acids is outlined, in its original form, in a paper published in 1907 and, in its final form, in his comprehensive article of 1910. The theory proposes that the reaction takes place in two major steps (a) the isomerization of the sugar, with loss of water, to an a-dicarbonyl compound, and (b) a benzilic acid type of rearrangement of the latter, with hydration, to the saccharinic acid. The second step involves chain rearrangement in the production of the saccharinic, isosaccharinic, and Kiliani s parasaccharinic acids, but not in the production of the metasaccharinic acids. 

It is interesting that Isbell s extension of the mechanism to the hexose 3,4-enediol series would explain the formation of Kiliani s parasaccharinic acid from this source. Indirect evidence is, however, available that the hexose 3,4-enediols are, at most, minor constituents of the hexose-alkali reaction mixtures. A 3,4-enediol (or the 3-hexulose with which it is in equilibrium) should give, by chain cleavage, formaldehyde and a pentose... 

CHjOH 1 CH2OH CH2OH Kiliani s Parasaccharinic acid... 

Tautomerisation further down the chain, to give a 3,4-enediolate, which then expels the C5 substituent, gives, after tautomerisation, a 5-deoxy-3,4-diketone. Base-catalysed cleavage of these gives parasaccharinic acids. These minor products can be detected only with modern analytical techniques, but illustrate the generality of the basic mechanism, which is illustrated in Figure 6.11. 

L-lyxo-fbrm. L-Parasaccharinic acid. fi-L-Galactometasaccharinic acid... 

---