Ketoses preparation

The reported yields in these ketose preparations range from less than 10% to around 50%. Nevertheless, this is the method of choice for preparing certain ketoses, especially where the starting aldose can be sacrificed. For some unknown reason, the best yields have consistently been obtained in the formation of D- Zwco-heptulose from D-j/Zj/cero-D-j/aZo-heptose. The procedure of Pratt, Richtmyer, and Hudson for preparation of this substance is given here. 

Some of the ketoses prepared in the FDP aldolase reactions can be converted to the corresponding aldolases catalyzed by glucose isomerase ( ) (from Miles), the enzyme used for the manufacture of high fructose com syrup. Figure 5 summarizes some of the isomerization reactions. The equilibrium mixture can be separated by Dowex-50-Ba column chromatography using water as the mobile phase. This isomerization step provides a new entry to several interesting aldolases. 

Although the Tollens reaction is a useful test for reducing sugars, it doesn t give good yields of aldonic acid products because the alkaline conditions cause decomposition of the carbohydrate. For preparative purposes, a buffered solution of aqueous Br2 is a better oxidant. The reaction is specific for aldoses ketoses are not oxidized by aqueous Br2. 

Oxidation of Isopropylidene Derivatives of Ketose Sugars. Whenever isopropylidene derivatives can be obtained in which all groups except the primary alcoholic grouping at Cl are blocked this method is undoubtedly the best. It may be illustrated by reference to the preparation of 2-keto-D-gluconic acid from D-fructose.14... 

The initiating reaction between aldoses and amines, or amino acids, appears to involve a reversible formation of an N-substituted aldosyl-amine (75) see Scheme 14. Without an acidic catalyst, hexoses form the aldosylamine condensation-product in 80-90% yield. An acidic catalyst raises the reaction rate and yet, too much acid rapidly promotes the formation of 1-amino-l-deoxy-2-ketoses. Amino acids act in an autocat-alytic manner, and the condensation proceeds even in the absence of additional acid. A considerable number of glycosylamines have been prepared by heating the saccharides and an amine in anhydrous ethanol in the presence of an acidic catalyst. N.m.r. spectroscopy has been used to show that primary amines condense with D-ribose to give D-ribopyrano-sylamines. ... 

On the other hand, borohydride reduction of the ketose o-fructose will give a mixture of o-glucitol and its epimer, D-mannitol. A better approach to D-mannitol would be reduction of the aldose D-mannose. o-Glucitol (sorbitol) is found naturally in the ripe berries of the mountain ash (Sorbus aucuparia), but is prepared semi-synthetically from glucose. It is half as sweet as sucrose, is not absorbed orally, and is not readily metabolized in the body. It finds particular use as a sweetener for diabetic products. o-Mannitol also occurs naturally in manna, the exudate of the manna ash Fraxinus ornus. This material has similar characteristics to sorbitol, but is used principally as a diuretic. It is injected intravenously, is eliminated rapidly into the urine, and removes fluid by an osmotic effect. 

Like nitromethane, 2-nitroethanol can be used as the methylene component for addition to aldehydes, giving epimeric nitrodiols in which the carbon chains have been lengthened by two carbon atoms. This reaction has attained preparative importance for the S5mthesis of higher-carbon ketoses 43,44) heptulose-phosphates 5) and of chloramphenicol... 

Rare or unnatural monosaccharides have many useful applications as nonnutritive sweeteners, glycosidase inhibitors and so on. For example, L-glucose and L-fructose are known to be low-calorie sweeteners. In addition, rare or unnatural monosaccharides are potentially useful as chiral building blocks for the synthesis of biologically active compounds. Therefore, these compounds have been important targets for the development of enzymatic synthesis based in the use of DHAP-dependent aldolases alone or in combination with isomerases. Fessner et al. showed that rare ketose-1-phosphates could be reached not only by aldol addition catalyzed by DHAP-dependent aldolases, but by enzymatic isomerization/ phosphorylation of aldoses [35]. Thus, for example, L-fructose can be prepared... 

Free aldonic acid nitriles have been prepared in a few cases. Kiliani obtained the cyanohydrin of D-fructose by adding hydrocyanic acid to the ketose and Miksic obtained the nitriles already mentioned in a similar way. 

The Lewis acid catalyzed C-glycosylation method is probably one of the most efficient to prepare C-glycosides of ketoses, the anomeric carbocation intermediate being in this case more stabilized by a further substituent. We applied this procedure to synthesize C-fructosides [15] (Scheme 8).The reaction of methyl... 

Unfortunately, this procedure did not permit preparation of the corresponding ketonucleosides postulated as key intermediates in many biosynthetic routes. In fact, -elimination reactions precluded the coupling of ketoses with nitrogen heterocycles. These difficulties may explain the scarcity of information concerning their biological properties or functions. 

Dialkyl dithioacetal derivatives of ketoses, such as D-fiuctose and L-sorbose, me inaccessible directly from the parent sugars, the ketose undergoing extensive decomposition under the conditions employed for mercaptaladon of aldoses. Such derivatives can, however, be prepared by indirect methods. Acetylation of D-fiuctose [40] and L-soibose with acetic adiydride and zinc chloride [41] leads to good yields of acyclic pentaacetates in which foe ketose carbonyl is not involved in a cyclic acetal. Subsequent treatment of these acetylated derivatives with thiols affords foe acetylated dialkyl dithioacetals in satisfactory yields, and conventional deacetylation affords foe unprotected dialkyl dithioacetals [40,41]... 

Mostly the baker s yeast transketolase has been used so far to prepare several valuable ketose sugars and derivatives 141 (cf. Sect. 7). Recently, the transketolase was utilized in the key stereogenic transformation of racemic 2-hydroxybutyraldehyde 142 into the homochiral synthon 5,6-dideoxy-D-t/ireo-hexulose 110 for the chemoenzymatic synthesis of (+ )-exo-brevicomin 107 [314], Transketolase has also been applied for the in-situ generation of Ery4P (35) from Fru6P (38) in a multi-enzymatic synthesis of 34 (Scheme 5). 

Table III gives preparations of six-, seven-, and eight-carbon ketoses, and their methylated, deoxygenated, azido, amido, and branched-chain derivatives. All these are first obtained as ketose phosphates, but this is not a severe restriction, for, apparently, enzymic hydrolysis with phosphatases is always successful. Phosphatases constitute a versatile group of enzymes, easily...

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