Of L-sorbose

Treatment of L-sorbose with anhydrous HF80 gave rise to an analogous mixture of products a-L-Sorp-1,2 2,l - 3-L-Sorp (12), (3-L-Sor/ l,2 2,l -a-L-Sorp (13), a-L-Sorf-1,2 2,l -a-L-Sorp, a-L-Sorp-1,2 2,l -a-L-Sorp, ct-L-Soif-... 

This reaction was explained on the basis of the formation ofyS-D-fructo-furanosyl fluoride (31), followed by the oxocarbonium ion 33. Similar treatment " of L-sorbose also gave, similarly, six L-sorbose anhydrides, involving 24, 26, 28, and 30, possibly all throu 32 and 34. The yields of 27 and 28... 

An alternative approach to increase the oxidation rate is the use of alkaline solutions, because bases enhance the reactivity of L-sorbose and weaken the adsorption strength of 2-KLG. Unfortunately, the rate enhancement at higher pH is accompanied by a drop in selectivity due to the poor stability of 2-KLG in alkaline solutions. To circumvent this problem, we have modified the platinum catalysts by adsorbed tertiary amines and carried out the oxidation in neutral aqueous solution [57], This allowed to enhance the rate without increasing the pH of the bulk liquid, which leads to detrimental product decomposition. Small quantities of amines (molar ratio of amine sorbose = 1 1700, and amine Pts = 0.1) are sufficient for modification. Using amines of pKa a 10 for modification, resulted in a considerable rate enhancement (up to a factor of 4.6) with only a moderate loss of selectivity to 2-KLG. The rate enhancement caused by the adsorbed amines is mainly determined by their basicity (pKa). In contrast, the selectivity of the oxidation was found to depend strongly on the structure of the amine. 

Figure 7. Effect of HMTA auxiliary. Selectivity to 2-KLG as a function of L-sorbose conversion over 5 wt% Pt/C. Unmodified catalyst ( ) catalyst modified with HMTA (O).

The variation in the antiscorbutic activity displayed by the various analogs of L-ascorbic acid makes it abundantly clear that the activity is dependent upon the stereochemical configuration of the molecule as a whole, and it would appear that the more closely the structure of a particular analog approaches that of the natural Vitamin C the greater will be the antiscorbutic power. Support for this view is illustrated by 6-desoxy-L-ascorbic acid which is obtained from L-sorbose.2 -80 Condensation of L-sorbose with acetone gives a mixture of 2,3-isopropylidene-L-sorbose (LII) and the diisopropylidene derivative. Treatment of LII with p-toluenesulfonyl chloride yields l,6-ditosyl-2,3-isopropylidene-L-sorbose (LIII). The greater reactivity of the tosyl group at C6 enables... 

Condensations of L-sorbose with ethyl acetoacetate and with ethyl pro-... 

The role of L-glycerose as a precursor of l sugars is doubtful, since it inhibits glycolysis in plants and animals, probably by the formation of L-sorbose 1-phosphate, which inhibits hexokinase.74-75... 

As may be seen from Fig. 2, it seems impossible to accommodate at the surface of the enzyme simultaneously a molecule of sucrose and of L-sorbose in such a way as to permit a switch of the fructosidic linkage... 

By far the most important oxidation of the hexitols is their specific biochemical transformation to ketoses. The history of this reaction dates from the fortuitous discovery of L-sorbose in mountain ash berries by Pelouze in 1852. It was not until twenty years later that Boussin-gault showed that it had arisen by bacterial oxidation of sorbitol. 

Sorbitol is of importance as a source of L-sorbose (VIII) for the synthesis of vitamin C. In addition, sorbitol has been used as a substitute for glycerol, as a humidifying agent in confectionery, for tobacco... 

The formation of melanoidins in yields exceeding 20% (on the basis of the free sugar involved in the reaction) is a noteworthy feature of this reaction in the 2-ketose field. Direct reaction of L-sorbose with ammonia gave only 2-3% of melanoidins, showing the special influ-... 

These spectra have detected only one species of L-sorbose in aqueous solution. However, after prolonged storage in methyl sulfoxide 5-10% of a second component is generated. Although it has not as yet been properly identified, there is no counterpart in spectra of the heptulose, and most likely it is the /f-pyranose—i.e., the existence of furanose forms of 1 and 2 should have about equal probability, whereas the / -pyranose form of 2 in a chair conformation should be much less stable than that of 1. 

The reaction of L-sorbose with acetone, a step in the synthesis of L-ascorbic acid (vitamin C), takes place in acetone solution [Eq. (41)] (361). 

Conversion of L-Sorbose into L-Ascorbic Acid by Way of Methyl... 

Other ketones and aldehydes have been used for preparing protected derivatives of L-sorbose that are structurally analogous to 26. These include cyclohexanone,113-115 formaldehyde,81,118 acetone,81, 118,117 benzaldehyde,81,118 and 1-methylcyclohexanone.115 The resulting acetals have been converted into L-ascorbic acid. 

An alternative procedure for the protection of L-sorbose (25), followed by oxidation at C-l and cyclization of the product to L-ascorbic acid, was developed by Hinkley and Hoinowski.257 L-Sorbose (25) was converted into methyl a-L-sorbopyranoside (37) by treatment with methanol and hydrogen chloride.258 Glycoside 37 was then oxidized with air in the presence of a suspension of platinum oxide in aqueous sodium hydrogencarbonate solution at 60°, to afford methyl ot-L-xylo-2-hexulopyranosidonic acid (38), which, when heated in hydrochloric acid, was converted into L-ascorbic acid (1), presumably by way of L-xy/o-2-hexulosonic acid (see Scheme 5). Acid 38 has also been prepared by oxidation of 37 with nitrogen tetraoxide.259,280 Yields were not reported for this reaction sequence, and it appears to offer no potential... 

Direct Oxidation of L-Sorbose to L-xylo-2-HexuIosonic Acid ( 2-Keto-L-gulonic Acid )... 

Clearly, an improved synthesis of L-ascorbic acid would result from the direct oxidation of L-sorbose (25) to L-xy/o-2-hexulosonie acid (28), thus eliminating the protecting-deprotecting steps currently required in the Reichstein-Griissner synthesis (see Scheme 4). Efforts to perform this oxidation may be divided into two categories, namely, chemical and fermentative. The results of each method will be summarized. 

L-Sorbose (25) has also been converted into 28 by using bacteria of the genera Achromobacter, Alcaligenus, and Serratia.29° From S. mar-cescens,290 2.8 g of 28 in 3.8 L of broth was produced in 10 days, starting with a 2% concentration of L-sorbose. It has been reported that Pseudomonas fluorescens No. 806 converts 25 into 28 in 25-35% yield.291 At the present time, the direct fermentation of 25 to 28 clearly is not efficient enough to compete with the Reichstein-Griissner, chemical procedure. 

It is apparent from the foregoing discussion that, at the present time, the direct chemical or fennentative oxidation of L-sorbose to h-xylo-2-hexulosonic acid is not efficient enough to compete with the Reich-stein-Griissner protection-oxidation method. 

For the conversion of D-glucitol (24) into L-xty/o-2-hexulosonic acid (28), several other methods, that do not proceed by way of L-sorbose, have been reported. 

It may be noted that l,2,3,4-tetra-0-benzoyl-5,6-0-isopropylidene-D-glucitol (52) has been oxidized with trityl tetrafluoroborate324 325 to 3,4,5,6-tetra-O-benzoyl-keto-L-sorbose (53) in 50% yield. This illustrates an interesting oxidation of acetals, and constitutes a partial, chemical synthesis of L-sorbose (25) from D-glucitol (24). 

When micro-organisms of the genus Acetomonas502 were grown in the presence of D-fructose (39), D-threo-2,5-hexodiulose (103) was the major product. The use of L-sorbose as a substrate has been reported525 to afford 103 as well. 

A. Ishizu, K. Yoshida, and N. Yamazaki, L-Galactosaccharinic acids new saccharinic acids formed by calcium hydroxide treatment of L-sorbose, Carbohydr. Res., 23 (1972) 23-29. 

Platinum-catalyzed oxidation of D-glucitol affords L-gulose and D-glucose. The specificity of this reaction is probably due to both statistical and steric factors. A related example is the conversion of L-sorbose into L-vy/o-2-hexulosonic acid in 62% yield (see Ref. 1, p. 1129). Similar oxidation of 1,2-acetals of a-D-glucofuranose and a-D-xylofuranose affords the respective glycuronic acids whereas, under more drastic conditions, the former acetal is converted into 1,2-O-isopropylidene-o -D-vy/o-hexofuranos-5-ulosono-6,3-lactone, a synthetic precursor of ascorbic acids. 

D-Glucose was reduced to the D-sorbitol with a hydrogen over Ni Raney, then it was turned into the L-sorbose with the acetobacter suboxydans and the hydroxyl groups of L-sorbose were protected with acetone treatment yielded the diaceton-L-sorbose. Subsequent treatment with NaOCI/Raney Ni produced di-O-isopropylidene-2-oxo-L-gulonic acid. Partial hydrolysis with aqueous HCI gave deprotected 2-oxo-L-gulonic acid, which yielded ascorbinic acid by heating with HCI. 

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