Aldoses, preparation from ketoses

Uloses are derivatives of carbohydrates, which contain a further keto group. Aldosuloses are obtained from aldoses and diuloses from ketoses. They are important intermediates in the synthesis of carbohydrates. Uloses can be prepared by oxidation of derivatives in which all the hydroxyls except that one subjected to oxidation are blocked. Uloses are formed as intermediates during pulp bleaching (see Section 8.1.3). 

Scheme 5.14. Glucose isomerase (GI) and fuculose isomerase (Fuc I) are used in the preparation of aldoses from ketoses.

The preparation of crystalline methyl ethers of iV-phenyl- or Af-p-tolyl-aldosylamine by condensation of aniline or p-toluidine with aldose methyl ethers proceeds, in many cases, readily and quantitatively in methanolic or ethanolic solution, either at room or reflux temperature. For this reason, such derivatives are frequently used to characterize aldose methyl ethers isolated during constitutional studies on polysaccharides. For D-glucose, for example, crystalline 2-0-methyl-, 6-0-methyl-,3,4-di-O-methyl-, 2,3,4-tri-O-methyl-, 2,4,6-tri-O-methyl-, " and 2,3,4,6-tetra-O-methyl-A-phenyl-n-glucosylamine have been prepared in this way. Although anomeric forms of A -arylaldosylamine methyl ethers are possible, such anomeric pairs have not been isolated. No similar derivatives have been obtained from ketose methyl ethers. 

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. 

A reagent prepared from 10 parts cone, hydrochloric acid, 8 parts acetic acid and 2 parts of a 10% solution of diphenylamine in ethanol, is added to the sugar-containing fractions in test tubes. The mixture is heated in a bath of boiling water, yielding a blue complex. Maximum colour intensity is attained after 5—10 min with ketoses and 30 min with aldoses. The mixture is cooled, made up to a fixed volume with acetic acid, centrifuged from silica gel and the light absorption measured at 640 nm. Standards and blanks are treated in the same way. 

Alditols are mainly produced from aldoses or ketoses by hydrogenation or reduction with amalgams, complex hydrides or by electrolytic reduction. Xyhtol is prepared by reduction of D-xylose obtained by hydrolysis of natural xylems (hemicelluloses), D-glucitol is prepared from D-glucose and D-mannitol via hydrogenation of D-fructose obtained from either starch or invert sugar. 

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. 

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]... 

Supplementary synthetic methods for preparing higher-carbon aldose and ketose sugars from the more accessible lower-carbon sugars are obviously desirable. The present review describes the recent development of two such methods based on the application to sugar... 

In the Lobry de Bruyn-Alberda van Ekenstein transformation (reviewed by Speck ) of a ketose to the epimeric aldoses, formation of the 3-deoxy-uloses is normally considered to be a side reaction, and both reactions are considered to proceed through a common intermediate, the 1,2-enediol of the sugar. Under the conditions used for preparation of the 3-deoxy-hexos-uloses from the diketose-(amino acids), the former were, however, the main products and the epimeric aldoses only minor products. Furthermore, under these conditions, both reactions were irreversible and the products so stable that the amounts of the two t3rpes of compound were a measure of their rates of formation. The rapid rate of decomposition of the diketose-(amino acids) was probably due to their ready enolization, even in the absence of strong alkali or acid, to give the 1,2-enolammonium compound... 

Other aldose/ketose isomerases with different substrate specificity have been cloned and overexpressedl86, including Fuc isomerase (Fuc I, EC 5.3.1.3) and Rha isomerase (Rha I, EC 5.3.1.14). Fuc isomerase, in combination with Fuc 1-P aldolase or Rha 1-P aldolase, has been used to prepare L-glucose, L-galactose, L-fucose, and derivatives from the corresponding L-glyceraldehyde derivatives and DHAP 87. ... 

We have developed preparative enzymatic syntheses of several unusual hexoketoses using fructose-1,6-diphosphate aldolase (FDP-aldolase, E.C.4.1.2.13) as catalyst and dihydroxyacetone phosphate (DHAP) and an aldehyde as substrates (15). The enzyme appears to be very specific for DHAP but will accept a variety of aldehydes as acceptors. The ketose-1-phosphates prepared are converted to the phosphate free ketoses after removal of the phosphate group by acid- or phosphatase-catalyzed hydrolysis. The ketoses can be isomerized stereospecifically to aldoses catalyzed by glucose isomerase (E.C.5.3.1.5.) from Flavobacteriuum arborescens. The equilibrium mixtures of aldoses and ketoses are then separated by chromatography on Dowex 50 (Ba ) or Dowex 1 (HSO "). Figure 1 illustrates the preparation of a mixture of 6-deoxy-6-fluoro-D-fructose... 

Another important value of the osazone-based approach is its utility in preparation of other ketosamines. Phenylosazones of many mono- and di-saccharides are readily prepared in high yields as pure crystalline materials from both aldoses and ketoses, and such kctosamincs as 1-amino-1-deoxy-L-sorbose, for example, can be synthesized most rationally from commercially available L-sorbose. ... 

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