Alditols,

1 Alditols - A review on homogenous catalysts used in the hydrogenation of aldoses with emphasis on mechanistic aspects of their activity and modes of their deactivation has appeared, and the hydrogenation of D-fructose to D-mannitol has been described using ruthenium molecular sieves modified with chiral ligands as catalysts.  

Density measurements of mannitol in potassium or sodium acetate solutions have revealed the nature of solute-solvent interactions in these mixtures and the kinetics of oxidation of several hexitols (and cyclitols) by molecular oxygen, catalysed by copper compounds, has been studied.  

A study has been conducted on the effects that sugar alditols and aminoalditols have on the rate of phosphate ester hydrolysis in the substrates bis(4-nitro-phenyOphosphate and supercoiled DNA, when catalysed by lanthanide cations. See Chapter 23 for the effect of solvents on the relative stabilities of the complexes formed between alditols and lanthanide cations. 

A hydrogenase from Alcaligenes entrophus coupled with a xylulose reductase from a yeast, have been used to produce xylitol from D-xylulose.  

The reaction of l,2 5,6-di-0-isopropylidene-D-mannitol with the metal oxo complex, (CsMesjReOs, in the presence of triphenylphosphine effected a deox-ydehydration reaction, and gave ( )-2. The same reaction applied to erythritol gave only 1,3-butadiene.  

Reduction of the carbonyl group of an aldose (or of the oxo group in a ketose) gives the series of alditols (called tetritols, pentitols, hexitols, etc., with 4, 5,6,. .., carbon atoms). 

Because of their higher symmetry compared to the aldoses, the number of possible isomers is lower, and some isomers are meso-forms, or, in the C, series, some isomers show pseudoasymmetry (further described in Chapter 7). 

Organic Chemist s Desk Reference, Second Edition 

FIGURE 5.2 The alditols derived from the C4, C5, and C6 monosaccharides in the D-series. Degenerate symmetry means that there are only three pentitols and six hexitols. 

Some isomers can therefore be named in more than one way. A choice is made according to a special carbohydrate rule that says that allocation to the D-series takes precedence over alphabetical assignment to the parent carbohydrate diastereoisomer. 

In order to avoid the formation of anomeric mixtures of derivatives, reducing sugars can be converted into alditols. If mixtures of sugars are analyzed by m.s. in combination with g.l.c., reduction of the sugars to alditols simplifies the separation. However, caution must be exercised, as two different aldoses may give the same alditol owing to symmetry properties. Every ketose affords two alditols on reduction. 

Systematic studies on the mass spectra of alditol acetates have revealed a simple mode of fragmentation for this class of compound. Alditol acetates do not give a molecular ion, but (M — CH3CO0 ) is found in a low abundance. The mass spectra of stereoisomers are almost identical and, therefore, the mass spectrum of D-glucitol hexaacetate (see Fig. 1) is representative of all peracetylated hexitols. 

The base peak in the specti a of all alditol acetates is the acetylium ion. 

The simple and well-established behavior of alditol acetates upon electron impact makes these derivatives suitable for identification of sugars. Thus, tetroses, pentoses, hexoses, and heptoses give characteristic spectra that can be fully interpreted. The presence and positions of deoxy groups or acetamido functions can readily be determined. Ambiguities 

Several laboratories routinely use alditol acetate derivatives for analyzing sugar mixtures by g.l.c. in combination with m.s. The usefulness of the method is illustrated by the following examples. Sugar analyses of lipopolysaccharides from Salmonella species have demonstrated that several chemotypes contain 3,6-dideoxyhexoses. When these sugars are converted into alditol acetates, the isomers can be separated by g.l.c., and their identity as 3,6-dideoxyhexoses can be established by 

The fact that each monosaccharide may give more than one peak owing to the formation of anomeric derivatives has led to a search for means to eliminate this complication. The anomeric center may be removed either by conversion into the oxime5 or the nitrile,394,3943 by oxidation followed by formation of the lactone (see Section IX, p. 71), or by reduction to the alditol. The last method is simpler than oxidation, and the separation of alditols and of aldononitriles will be discussed here additional examples are given in Table V (see p. 119). The early work on the separation of alditols has been discussed by Bishop.4 The necessity of decomposing borate complexes 

One of the consequences of forming a cyclic hemi-acetal or hemiketal is that the nucleophilic hydroxyl adds to the carbonyl group and forms a new hydroxyl. This new group is susceptible to many normal chemical reactions of hydroxyls, e.g. esterification, and this type of reaction effectively freezes the carbohydrate into one anomeric form, since the ringopening and equilibration can now no longer take place. Consider esterification of glucose with acetic anhydride (see Section 7.9.1). P-o-Glucose will be 

Reduction of the aldehyde or ketone group in a sugar is readily achieved using a variety of reducing agents. Reduction occurs on the small amount of open-chain form present at equilibrium. As the open-chain form is removed, the equilibrium is disturbed until total reduction is achieved. The products are polyhydroxy compounds termed alditols. Reduction 

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. 

A mixture of 2-C-hydroxymethylglycerol, 2,4-bis-C-hydroxymethylpentitol, and 3-C-hydroxymethylpentitol has been isolated from a calcium hydroxide-catalysed formose reaction from which most of the calcium ions were removed as sparingly soluble salts or chelates at the end of the induction period/ 

Lactitol has been prepared by catalytic or borohydride reduction of lactose, and their properties have been compared lactitol was found to be much less readily consumed by microorganisms, probably reflecting a lower 3-galacto-sidase efficiency with this substrate.  

A number of methyl or benzyl ether derivatives of galactitol have been prepared and converted into acetyl derivatives for mass spectral study. HN.m.r. investigation of the product obtained from chloroacetaldehyde diethyl acetal and galactitol (see Vol. 1, p. 46) has shown it to be the 1,3 4,6-di-0-acetal derivative, which on boiling with ethanolic sodium hydroxide yielded the polycyclic acetal-ether (3).  

The configurations of a series of 2- and 5-substituted derivatives of 1,4 3,6-dianhydro-hexitols (4) have been established from their C n.m.r. spectra. Crystal structure measurements have shown thatl,5-anhydro-2,3,4-tri-0-benzoyl-xylitol and -ribitol both adopt the expected Ci(d) conformation, whereas l,2,3,4-tetra-0-benzoyl-/3-D-xylopyranoside adopts the alternative C4 form, emphasizing the importance of the anomeric effect in the latter case. Unsaturated alditol derivatives are mentioned in Chapter 12. 

The synthesis of cyclitols from 5-dicarbonyl sugars has been reviewed.  

6-Deoxy-altritol has been shown to be present in the cell wall polysaccharide of t ocardia asteroides, along with arabinose, galactose, and glucose, the first reported occurrence of this alditol in 

The preparation of D-mannitol from standard monosaccharides and the processing of hardwoods for producing xylitol and other polyols and monosaccharides have been reviewed. The hydrogenation of xylose to xylitol over a molybdenum-promoted copper catalyst and 

A stereoselective aldol condensation with the boryl thio-ester derivative (5) gave the syn isomer (6) of the 2-deoxy or 2-C-branched 12 

The use of ( )-malic acid as a source of 2-deoxy-D-erythro-tetrose and hence 1,2-anhydro-3-deoxypentitols en route to milbemycin is mentioned in Chapter 24. 

The deamination of 2-amino-2-deoxy-D-galactitol has been studied both C-3 epimers (xylo and lyxo) of the corresponding 2-deoxy-hexitol could be detected, depending on the conditions, besides other minor constituents these results are significant for deamination studies on mucus glycoproteins containing such amino-hexitol units. 

A new branched-chain nonitol, calditol, assigned the structure (1), has been isolated as a component of the lipids in Calderella thermoacidophile bacteria, in which it provides the hydrophilic tail the stereochemistry was not determined. The effects of pH, solvent, and catalyst treatment on the Raney nickel-catalysed hydrogenation of xylose to xylitol has been studied, and the factors governing this process have been reviewed. The yields of D-mannitol obtained by 

5- and 3,4-Di-O-acyl-D-mannitol derivatives have been prepared conventionally using standard saturated fatty acids in a study of their surfactant properties.  

The X-ray irradiation of xylitol, sorbitol, and dulcitol single crystals has been studied.  

Fernandez-Bolanos, F. Collantes de Teran Palacios, R. Sanchez-Lopez, and N. Bueno Iborra, j4m. Quim., 1979, 75, 1013 Chem. Abstr., 1980, 93, 26 680). 

Imura and K. Ishimoto, Kumamoto Joshi Daigaku Gakujutsu Kiyo, 1977, 29, 55 (Chem. Abstr., 1980, 92, 111 239). 

Reagents i, MnOj-CHClj ii, HjOj-HO iii, p-NOjC H COjH iv, NaBH v, NaOH 

Radical-initiated reduction of peracetylated glycopyranosyl bromides with tributyltin hydride has provided a route to the corresponding 1,5-anhydro-pentitols and -hexitols, including 2,3,4,6-tetra-0-acetyl-l,5-anhydro-D-iditol. ° 

Nadirov and R. L. Slutskin, Catalytic Hydrogenation and Hydrogenolysis of Carbohydrates , Khimiya, Moscow, 1976 Chem. Abs., 1977, 87, 202 015r). 

Several 8-chloro-7-trifluoromethylisoalloxazines (456) have been synthesized by the reaction of 1-amino-1-deoxy-hexitols and -pentitols with 2,4-dichloro-5-nitrotrifluoromethylbenzene, followed by reduction of the nitro-group of the product with Raney nickel and cyclization with alloxan.  

Complexes of lithium aluminium hydride with l,4 3,6-dianhydro- and 1,3 4,6-di-O-benzylidene-D-mannitol, each of which contains a two-fold axis of symmetry, have been used to achieve asymmetric reductions of some alkyl aryl and dialkyl ketones e.g. methyl or ethyl phenyl ketone and 3,3-dimethylbutan-2-one). All reductions with lithium l,4 3,6-dianhydro-D-mannitolatodihydridoaluminate(iii), using a 2 1 molecular ratio of ketone to reducing agent, gave the 5-enantiomer of the secondary alcohol preferentially (selectivity 1.1—5.3 %), whereas those of alkyl aryl ketones and dialkyl ketones gave more of the 5- and R-alcohols, respectively, when lithium l,3 4,6-di-0-benzylidene-D-mannitolatodihydridoaluminate(iii) was used. 

A review on the preparation, properties, reactions, and uses of polyhydric sugar alcohols has appeared.  

A new antibiotic which is a 1,6-diester derivative of D-mannitol is mentioned in Chapter 18. 

A method for the electrochemical reduction of D-xylose to 2-deoxy-D-r/rr o-pentitol has been described. The homogeneous hydrogenation of sugars using tris-triphenylphosphine ruthenium chloride is improved in the presence of hydrogen chloride, which inhibits competitive decarbonylation of the sugar. L-(2,3)-Threitol is easily prepared from ( + )tartaric acid by lithium aluminium hydride reduction of the 2,3-0-isopropylidene derivative of diethyl tartrate, followed by acid hydrolysis of the resultant ketal.  

A set of modified conditions has allowed some control over the complex formose reaction so that the branched-chain alditols (6)—(8) represented the major products formed initial catalysis was effected with calcium hydroxide, which was removed at the end of the induction period with oxalate, and the reaction was then adjusted to pH 12 with potassium hydroxide.  

The di-aryl D-glucitol derivative (9) was one of the products isolated from reaction of D-glucose with phenol in acid solution (see also Chapter 3). 

In the phloem sap of Betula pendula at 0°C, sugars found (in order of concentration) were D-fructose sucrose stachyose D-glucose maltose raffinose, while in the xylem sap the order was D-fructose D-glucose sucrose stachyose (149). The ubiquitous occurrence of D-glucose and D-fruc-tose is exemplified by its presence in sap (149, 150), bark (179), roots (109), and trunkwood (93). 

D-Galactose has been found in Siberian larch Larix sibirica) wood (28), the spring sap of birches Betula spp.) (103, 149), the xylem of Scots pine Pinus sylvestris) (27), and red beech Fagus sylvatica) sap (150). D-Mannose has been found in saps (149, 150). Both may be more widespread than indicated. 

Of the pentoses, L-arabinose has been found in the heartwood and sapwood of many species of both angiosperms and gymnosperms (7, 27, 73, 160). The nutritive sap of pine is reported to contain a small amount of D-xylose (112). Traces of D-xylose were also found in the symplast of Betula pendula (149). 

Traces of L-rhamnose and L-fucose were found in the xylem of Pinus sylvestris (27). These sugars, along with L-arabinose and D-galactose with which they were found, could have arisen from the breakdown of pectic substances (Sect. 4.10.2) or phenolic glycosides (Sect. 4.8). Traces of the D-ribose have been found in both the symplast and apoplast of Betula pendula (50). 

Alditols are acyclic, polyhydric alcohols. They are classified according to the number of carbon atoms they contain. Members of the tetritol (4 carbon atoms) to octitol (8 carbon atoms) families are known to occur in plants, with the hexitols being the most common. The distribution of alditols and anhydrohexitols and their use in taxonomy has been reviewed (137). 

Configurationally chiral cryptands have been synthesized from carbohydrate precursors e.g. l,2 5,6-di-0-isopropylidene-D-mannitol was transformed into 

The synthesis of 5-(tetra-0-acetyl-L-amZ / u-tetritol-l-yl)tetrazole, e/c., by reaction of acetylated aldononitriles with ammonium azide has been noted in Chapter 10. Related pentitol-l-yl heterocyclic compounds have been prepared 

The properties, synthesis, stability, and metabolism of l,4 3,6-dianhydro-D-glucitol dinitrate have been discussed. The i.r. and Raman spectra of powdered 1,5-anhydro-xylitol, -ribitol, and -L-arabinitol have been reported Raman spectra were also recorded for solutions of the anhydro-sugars in water and in [ HeJDMSO.  

Silvieri and N. J. Deangelis, Analyt. Profiles Drug SiAst., 1975, 4, 225 Chem. Abs., 

Fractionation of extracts of Convolvulus glomeratus afforded a new branched-chain alditol, 2-C-methyl-D-erythritol, whose constitution and absolute configuration were deduced by and n.m.r. spectroscopy, c.d. measurements, and synthesis.  

The complete degradation of alditols into formic acid with alkaline hydrogen peroxide and a ferrous salt is referred to in Chapter 22, and the determination of pentitols by a procedure involving periodate oxidation is also mentioned in that chapter.  

D-Glucitol has been found primarily in the endosperm of maize 

Biosynthesis of riboflavin (A) using D-[l- C]ribose revealed labels mainly as Indicated. 

The effect of pressure on the hydrogenation of glucose in 80 aqueous isopropanol over Raney nickel has been investigated, while the reaction kinetics of a three-phase slurry, catalytic hydro- 

D-pentitols, and 2-amino-2-deoxy-D-pentltols by the same asymmetric 

3- -Allyl- and -benzyl-D-mannltol have been synthesized from a partially protected D-mannltol derivative, while 1,2,3j5j6-penta-0- 

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The carbonyl group of carbohydrates can be reduced to an alcohol function Typi cal procedures include catalytic hydrogenation and sodium borohydnde reduction Lithium aluminum hydride is not suitable because it is not compatible with the solvents (water alcohols) that are required to dissolve carbohydrates The products of carbohydrate reduc tion are called alditols Because these alditols lack a carbonyl group they are of course incapable of forming cyclic hemiacetals and exist exclusively m noncyclic forms... 

The reaction is used for the chain extension of aldoses in the synthesis of new or unusual sugars In this case the starting material l arabinose is an abundant natural product and possesses the correct configurations at its three chirality centers for elaboration to the relatively rare l enantiomers of glucose and mannose After cyanohydrin formation the cyano groups are converted to aldehyde functions by hydrogenation m aqueous solution Under these conditions —C=N is reduced to —CH=NH and hydrolyzes rapidly to —CH=0 Use of a poisoned palladium on barium sulfate catalyst prevents further reduction to the alditols... 

Alditol (Section 25 18) The polyol obtained on reduction of the carbonyl group of a carbohydrate Aldol addition (Section 18 9) Nucleophilic addition of an aldehyde or ketone enolate to the carbonyl group of an aide hyde or a ketone The most typical case involves two mole cules of an aldehyde and is usually catalyzed by bases... 

Table 2. Price of Sucrose, Alditols, and Synthetic Sweeteners...

Sucrose occupies a unique position in the sweetener market (Table 3). The total market share of sucrose as a sweetener is 85%, compared to other sweeteners such as high fmctose com symp (HFCS) at 7%, alditols at 4%, and synthetic sweeteners (aspartame, acesulfame-K, saccharin, and cyclamate) at 4%. The world consumption of sugar has kept pace with the production. The rapid rise in the synthetic sweetener market during 1975—1995 appears to have reached a maximum. 

The small optical rotations of the alditols arise from the low energy barrier for rotation about C—C bonds, permitting easy iaterconversion and the existence of mixtures of rotational isomers (rotamers) ia solution (12). 

Teichoic acids (16) are bacterial polymers in which alditols, glycerol, or ribitol are joined through the primary hydroxyl groups via phosphate diester linkages. 

Reduction. Mono- and oligosaccharides can be reduced to polyols (polyhydroxy alcohols) termed alditols (glycitols) (1) (see Sugar alcohols). Common examples of compounds in this class ate D-glucitol (sorbitol) [50-70-4] made by reduction of D-glucose and xyhtol [87-99-0] made from D-xylose. Glycerol [56-87-5] is also an alditol. Reduction of D-fmctose produces a mixture of D-glucitol and D-mannitol [69-65-8],... 

Alditols are sweet. Xyhtol has essentially the same sweetness as sucrose sorbitol is about half as sweet as sucrose. In chewing gum, polyols provide texture, sweetness, and mouthfeel and reduce the iacidence of dental caries. 

Reduction (Section 25.18) The carbonyl group of aldoses and ketoses is reduced by sodium borohydride or by catalytic hydrogenation. The products are called alditols. 

Alditol (Section 25.18) The polyol obtained on reduction of the carbonyl group of a carbohydrate. 

Treatment of an aldose or ketose with NaBH4 reduces it to a polyalcohol called an alditol. The reduction occurs by reaction of the open-chain form present in the aldehyde/ketone hemiacetal equilibrium. Although only a small amount of the open-chain form is present at any given time, that small amount is reduced, more is produced by opening of the pyranose form, that additional amount is reduced, and so on, until the entire sample has undergone reaction. 

D-Glucitol, the alditol produced by reduction of D-glucose, is itself a naturally occurring substance present in many fruits and berries. It is used under its alternative name, D-sorbitol, as a sweetener and sugar substitute in foods. 

Problem 25.17 I Reduction of D-glucose leads to an optically active alditol (D-glucitol), whereas reduc-I tion of D-galactose leads to an optically inactive alditol. Explain. 

Problem 25.18 I Reduction of L-gulose with NaBH4 leads to the same alditol (D-glucitol) as reduction of D-glucose. Explain. 

Much of the chemistry of monosaccharides is the familiar chemistry of alcohols and aldehydes/ketones. Thus, the hydroxyl groups of carbohydrates form esters and ethers. The carbonyl group of a monosaccharide can be reduced with NaBH4 to form an alditol, oxidized with aqueous Br2 to form an aldonic acid, oxidized with HNO3 to form an aldaric acid, oxidized enzymatically to form a uronic acid, or treated with an alcohol in the presence of acid to form a glycoside. Monosaccharides can also be chain-lengthened by the multistep Kiliani-Fischer synthesis and can be chain-shortened by the Wohl degradation. 

What other d aldohexose gives the same alditol as D-talose ... 

The mass spectrum of alditol acetates are easy to interpret as they fragment at each C—C bond as shown. 

The polyhydric alcohols arising formally from the replacement of a carbonyl group in a monosaccharide with a CHOH group are termed alditols (see 2-Carb-19). 

The term polysaccharide has also been widely used for macromolecules containing glycose or alditol residues in which both glycosidic and phosphate diester linkages are present. 

If the anomeric hydroxy group is replaced by a hydrogen atom, the compound is named as an anhydro alditol (2-Carb-26). 

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- . 

The alditols from fucose and rhamnose are frequently termed fucitol and rhamnitol (see 2-Carb-19.1). 

The imino analogue of a monosaccharide may be named as an imino-substituted deoxy alditol. 

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