D,L-Sorbose

Along with their researches on alkaline isomerization, Lobry de Bruyn and Van Ekenstein21 prepared crystalline D,L-sorbose by evaporating an aqueous solution of the d- and L-isomers. The crystals were later shown to be a racemate compound66 from solubility data. 

A photochemical71 synthesis of an optically inactive ketohexose has been reported by the action of sunlight on an aqueous solution of formaldehyde and oxalic acid, for fifteen months, in a sealed tube. The melting point of the phenylosazone (164°), was believed to indicate the formation of D,L-sorbose, but this evidence is of doubtful value at the present time.11... 

Most current industrial vitamin C production is based on the efficient second synthesis developed by Reichstein and Grbssner in 1934 (15). Various attempts to develop a superior, more economical L-ascorbic acid process have been reported since 1934. These approaches, which have met with htde success, ate summarized in Crawford s comprehensive review (46). Currently, all chemical syntheses of vitamin C involve modifications of the Reichstein and Grbssner approach (Fig. 5). In the first step, D-glucose (4) is catalytically (Ni-catalyst) hydrogenated to D-sorbitol (20). Oxidation to L-sotbose (21) occurs microhiologicaRy with The isolated L-sotbose is reacted with acetone and sulfuric acid to yield 2,3 4,6 diacetone-L-sorbose,... 

Sterile aqueous D-sorbitol solutions are fermented with y cetobacter subo >gichns in the presence of large amounts of air to complete the microbiological oxidation. The L-sorbose is isolated by crystallisation, filtration, and drying. Various methods for the fermentation of D-sorbitol have been reviewed (60). A.cetobacter suboyydans is the organism of choice as it gives L-sorbose in >90% yield (61). Large-scale fermentations can be carried out in either batch or continuous modes. In either case, stefihty is important to prevent contamination, with subsequent loss of product. 

FIGURE 7.4 D-Fructose and L-fructose, an enantiomeric pair. Note that changing the configuration only at C5 would change D-fructose to L-sorbose. 

The main drawback of the system is that the ketone catalyst slowly decomposes during the reaction, which means that 0.2-0.3 equivalents are needed for complete conversion. More robust catalysts, which can be used in 1-3 mol%, have recently been reported, but have not as yet been widely applied [8]. Ketone 1 is commercially available, or can easily be synthesized in large scale in two steps from d-fructose. Ent-1 is obtained in a similar way from L-sorbose. 

L-Sorbose + NADP+ = 5-dehydro-D-fmctose + NADPH (reaction of sorbose dehydrogenase, EC 1.1.1.123)... 

In 1952, Wolfrom and Hilton demonstrated that L-sorbose was also capable of forming dimeric dianhydrides,22 and they postulated sorbofuranosyl and pyra-nosyl cationic intermediates. In 1955, Boggs and Smith23 postulated a fructofu-ranosyl cationic intermediate in the formation of per-O-acetyl ot-D-Fru/-1,2 2,l -p-D-Fru/[di-D-fructose anhydride I (5)] from inulin triacetate. They indicated that three adjacent P-2,l -linked fructofuranosyl units would be required for formation of the dianhydride. 

When D-fructose and L-sorbose are refluxed with aqueous HC1, dihexulose dianhydrides are formed.91 If the water is replaced by N./V-dimethylformamide, substantially increased yields are obtained and 1,2-linked disaccharides are detected. Higher yields of dianhydrides were obtained from fructose, rather than sorbose, under comparable conditions. Treatment of levan with dilute H2S04 at 60°C yielded92 a-D-Fru/-l,2 2,1 -fi-D-Fru/(5). Presumably, any products that contain 2,6-linkages with large central rings would rapidly isomerize to the more stable 1,2-linked product. 

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... 

Direct Oxidation of Ketose Sugars. The primary alcoholic group at Cl adjacent to the keto group at C2 of a ketose sugar such as D-fructose (XXI) or l-sorbose, is more sensitive to oxidation than the other primary alcoholic group at C6 or secondary alcoholic groups at C3, C4, and C5. 

Dihydroxyacetone phosphate reacts with D-glycerose in the presence of aldolases of muscle and liver to give D-fructose 1-phosphate (XII) exclusively, whilst DL-glycerose forms equimolar proportions of D-fructose 1-phosphate (XII) and L-sorbose 1-phosphate (XIII).65 Specificity of the enzyme is interesting in the light of Fischer and Baer s observations66 in... 

L-Galactose is probably not produced from L-glycerose, since the latter inhibits glycolysis and, even so, reaction with dihydroxyacetone phosphate in the presence of aldolase yields L-sorbose 1-phosphate which, on stereochemical grounds, is also an unlikely precursor. A more plausible route is direct conversion from D-galactose (XXI) by complete reversal of stereo-... 

D-isoascorbic acid D-mannitol D-mannose D-quinic acid D-ribolactone D-ribose D-saccharic acid D-sorbitol L-sorbose D-xylose (—)-a-Pinene (+)-a-Pinene (—)-/ -Pinene (i )-(+)-pulegone... 

The ketone catalyst is readily prepared from D-fructose by ketalization and oxidation. The other enantiomer of this ketone, prepared from L-sorbose,... 

From a structural point of view, the carbohydrate template can have either furan or pyran rings although in some cases open chain structures can be formed. A large variety of aldopentoses (e.g. d- and L-arabinose, D-ribose, D-xylose), aldohexoses (e.g. D-glucose, D-mannose, D-galactose) as well as ketohexoses (e.g. D-fructose, L-sorbose) can be used as scaffolds. 

Blocking the C-l OH of D-fructose and L-sorbose (Scheme 25) was effected in excellent yields through regioselective isopropylidene acetalation of the free ketoses, followed by etherification (benzylation or allylation) of the remaining primary alcohol. Acid-catalyzed hydrolysis of the isopropylidene groups and condensation with HSCN efficiently produced a sole fused bicyclic OZT. 

In the continuation of this work, a broad range of OZTs was prepared from selectively protected derivatives of D-fructose and L-sorbose (Scheme 26).47... 

It is noteworthy that D-fructose, which has a pyranose structure in the free crystalline state, assumes a furanose configuration whenever it combines with another sugar to form an oligosaccharide or polysaccharide. Apparently the ketohexose L-sorbose shows the same behavior. 

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