Alditol from aldoses

Hydrazones 10 derived from aldose monosaccharides (9) and 2-hydrazinopyrimidine (8) gave, upon oxidative cyclization with bromine in methanol, the corresponding 3-(alditol-l-yl)-l,2,4-triazolo[4,3-a]pyrim-idines 11 [97JHC(34)1115] (Scheme 7). 

Bromine (hypobromite) and hypoiodite oxidations are particularly useful for the preparation of aldonic acids from aldoses and of aldaric acids from glycuronic acids. Primary alcohol groups also undergo oxidation by these reagents, although this conversion is of less value glycosides can thus be converted into glycosiduronic acids, and alditols into aldoses and aldonic acids. 

Aldoses and ketoses can be reduced to alditols by various agents for which purpose sodium borohydride is very useful. For industrial production of alditols, however, catalytic hydrogenation is applied. Only one product is formed from aldoses, whereas ketoses give rise to two diastereoisomers because of the generation of a new asymmetric center (Fig. 2-26). Sodium borohydride can also be used for reduction of carbonyl groups in polysaccharides. 

Although lactones may be reduced electrochemically or via Bouveault-Blanc reactions to produce diols, such reactions are more frequently used to prepare lactols. Both cathodic (Hg or Pb) and Na/Hg reduction are useful in the preparation of alditols from aldonic acid y-lactones. The reductions may be easily stopped at the intermediate aldose stage. ... 

The anomeric forms derived from equilibration of aldoses give rise to multiple peaks when trimethylsilylated and gas chromatographed [311]. A method of overcoming this problem, assuming that mutarotation itself is not under study, is to modify the aldose. It can be oxidised and lactonised to the aldonolactone, for example, and characterised as its TMS derivative [322]. Alternatively for the identification of aldoses and alditols, more use may be made in the future of the separations achievable on open tubular columns of the poly-0-acetylaldonic nitriles (18) produced from aldoses and the poly-acetyl esters from alditols [323]. Figure 1.18 shows the separation of 32 assorted polyols and aldoses. 

Conversion of alditols to aldoses without the need to protect all hydroxy groups has been achieved by monotosylation of one primary hydroxy group, displacement with azide ion and photolysis in methanol to yield the aldimine,which was then hydrolyzed to the aldose. The procedure was illustrated using 3 4-0 isopro ylideno-D-mannitol to produce D-mannose. The synthesis of D-[U- Cjgalactose from methyl <-D-[n- Cjglucopyranoside via aqueous bromine oxidation to the 4.-uloside, reduction by sodium borohydride and hydrolysis has been described, along with the isolation of D-glucuronic acid and methyl o( D-mannopyranoside as by-products. 

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. 

Aldotetrose B must be D-threose because the alditol derived from it (o-threitol) is optically active (the alditol from D-erythrose, the other possible D-aldotetrose, would be meso). Due to rotational symmetry, however, the alditol from B (D-threitol) would produce only two NMR signals. Compounds A-F are thus in the family of aldoses stemming from D-threose. Since reduction of aldopentose A produces an optically inactive alditol, A must be D-xylose. The two diastereomeric aldohexoses C and D produced from A by a Kiliani-Fischer synthesis must therefore be D-idose and D-gulose, respectively. E and F are the alditols derived from C and D, respectively. Alditol E would produce only three C NMR signals due to rotational symmetry while F would produce six signals. 

The name of an aldose derivative in which the aldehyde group has been replaced by a terminal CH3 group is derived from that of the appropriate alditol (see 2-Carb-19) by use of the prefix deoxy- . 

If the same alditol can be derived from either of two different aldoses, or from an aldose or a ketose, preference is ruled by 2-Carb-2.1 or 2.2.2 as appropriate. 

Diols and polyols can participate in equilibria with boric acid in aqueous solution. The stability of polyolborates is determined by the number of OH groups in cis positions. Complexes with polyols are more stable than with diols, and 1,2-diol complexes are more stable than their 1,3-diol counterparts (Table 10) since the resulting five-membered chelate ring is unstrained.75120 In the case of 1,3,5-triols stable cage-like structures (5) and (6) are favored. Open-chain or five-membered cyclic polyols form more stable chelate complexes than their six-membered counterparts.120 Thus, chelates from alditols and ketohexoses are more stable than the corresponding aldose chelates (Table 10). Many polyols allow quantitative titrimetric determination of boric acid. Of these, mannitol remains the most widely used reagent on the basis of availability, cost and ease of handling.75... 

Fig. S.30. Gas chromatogram of alditol trifluoroacetates produced from a standard mixture of the parent aldoses. Peaks 1 = fucose 2 = ribose 3 = arabinose 4 = xylose 5 = mannose 6 = glucose ...

A different type of reduced sugar is an alditol, in which the aldehyde group of an aldose has been reduced. For example, the alditol produced from D-glucose is D-glucitol (the trivial name is sorbitol). The name of an alditol is obtained by adding -itol to the root of the name of the aldose (except for glycerol, a reduction product of glyceraldehyde). 

At American University, Harriet Frush and Horace Isbell worked on the mechanism of oxidation of carbohydrates by peroxides. They discovered that, in aqueous alkaline hydrogen peroxide, aldoses are quantitatively degraded to formic acid, so that hexoses produce six moles of this acid and pentoses produce five moles. A detailed study of the mechanism of the reaction revealed that degradation takes place by several pathways, the most rapid one involving the formation of peroxy radicals and hydroxy radicals. Thus, when a hydroperoxide-aldose adduct reacts with hydrogen peroxide, a peroxy radical is formed, which decomposes to a hydroxy radical, formic acid, and the next lower aldose. It was also found that, under basic conditions, hydroxy radicals oxidize alditols and aldonic acids to carbonyl compounds in much the same way they do with Fe2+ in the Fenton reaction. During the years she spent at American University, Dr. Frush was able to publish 10 papers without help from any research assistant or laboratory technician. This brought her total to more than 70 papers. 

A more common procedure for aldoses is their reduction with sodium borohydride to alditols and submission to GC-MS after conversion to TMS ethers [324], permethyl ethers, acetates or trifluoroacetates. This method was successfully employed in studies of the mechanism of conversion of deoxythymidine diphosphate D-glucose to deoxythymidine 4-oxo-6-deoxy-D-glucose by an oxidoreductase from E. coli [325]. An in-... 

In summary, it can be said that, in homogeneous alkaline solution, either methanolic or aqueous, an equilibrium is established between the aldose, nitromethane, and deoxynitroalditols, and that, for successful addition, this equilibrium must be displaced in favor of the alditols, either through precipitation of their sodium salts from methanolic solution, or by direct crystallization from aqueous solution. Because of these requirements, the method is not so widely applicable as the cyanohydrin synthesis, but, for selected sugars, such as n-gZgcero-D-ZaZo-heptose and o-erythro-i -manno-octose, its simplicity and the satisfactory yields obtained make it the method of choice. 

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