Sodium borohydride aldoses reduction

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. 

Reductions with sodium amalgam are fairly mild. Only easily reducible groups and conjugated double bonds are affected. With the availability of sodium borohydride the use of sodium amalgam is dwindling even in the field of saccharides, where sodium amalgam has been widely used for reduction of aldonic acids to aldoses. 

Reduction of a ketose yields a secondary alcohol, and reduction of an aldose yields a primary alcohol (ccilled an alditol). A possible reducing agent is hydrogenation in the presence of a catalyst, such as platinum another reducing agent is sodium borohydride (NaBH ) followed by hydrolysis. Figure 16-14 illustrates the formation of an alditol. 

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. 

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-... 

Unprotected aldoses and ketoses can be reduced to afford alditols while aldonolactones can be reduced to give either aldoses or alditols. The reagent of choice for reduction to alditols is sodium borohydride since it is both cheap and convenient to use. The reduction is carried out under mild conditions at room temperature in an aqueous solution. Sodium borohydride is stable in water at pH 14 while it reacts with the solvent at neutral or slightly acidic pH, but at a slower rate than the rate of carbonyl reduction. In some cases, the product will form esters with the generated boric acid. These borate complexes can be decomposed by treatment with hydrochloric acid or a strongly acidic ion-exchange resin and the boric acid can be removed in the work-up as the low boiling trimethyl borate by repeated co-evaporation with methanol at acidic pH [155]. 

The reduction of aldoses/ketoses occurs readily with sodium borohydride and during the reaction the pH increases to about 9 (O Scheme 19) [155]. For the reduction of aldonolactones in water the first step of the reduction has to be carried out at a pH around 5 in order to avoid ring-opening of the lactone to the corresponding sodium salt which will not react with sodium borohydride. The pH control can be achieved by performing the reduction in the presence of an acidic ion-exchange resin, e. g., Amberlite IR-120 [156]. In this way, it is possible to stop the reduction at the aldose step. Alternatively, more sodium borohydride can be added and thereby increasing the pH to 9 by which the alditol is obtained (O Scheme 19). The reduction of aldonolactones to alditols can also be performed in anhydrous methanol or ethanol where hydrolysis of the lactone is not a side reaction [156]. 

The non-catalytic reduction of aldonolactones to the corresponding aldoses and/ or alditols by sodium borohydride or lithium aluminum hydride has also been studied [1]. Because of the stoichiometric character of these procedures they are, however, limited to laboratory use. 

A review of the preparation, structures, and stereochemistry of cyclic acetals of the aldoses and aldosides has appeared. Pyridinium toluene-p-sulphonate has been reported to be a mild catalyst for the formation and cleavage of dioxolane-type acetals, although no carbohydrate examples were quoted. Acetals and ketals of carbohydrates have been used as co-agents to introduce chirality into the products of sodium borohydride reduction of acetophenone, propiophenone, etc ... 

Tetroses and Pentoses - 4-0- -Butyldimethylsilyl-2,3-0-isopropylidene-L-threose (1) has been prepared in seven efficient steps from o-xylose. 3,4-0-Isopropylidene-D-eythrulose (4) has been synthesized from the known tetritol derivative 2 by primary protection as the silyl ether 3, followed by Dess-Martin oxidation and desilylation. Compound 2 was derived from D-isoascorbic acid (see Vol. 22, p. 178, refs. 9,10). In a similar reaction sequence, the enantiomer 5 has been obtained from L-ascorbic acid. The dehomologation of several di-0-isopropylidenehexofuranoses e.g., 6- 7) has been carried out in two steps without intermediate purification, by successive treatment with periodic acid in ethyl acetate, followed by sodium borohydride in ethanol. Selective reduction of 3-deoxy-D-g/jcero-pentos-2-ulose (8) to 3-deoxy-D-g/> cero-pent-2-ose (9) has been achieved enzymically with aldose reductase and NADPH." 4-Isopropyl-2-oxazolin-5-one (10) is a masked formaldehyde equivalent that is easily converted to an anion and demasked by mild acid hydrolysis. One of the three examples of its use in the synthesis of monosaccharides is shown in Scheme 1. ... 

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. 

The carbonyl group of aldoses and ketoses can be reduced by various reagents. The products are polyols, called alditols. For example, catalytic hydrogenation or reduction with sodium borohydride (NaBH4) converts D-glucose to D-glucitol (also called sorbitol review Sec. 9.12). 

Reduction of the sugar acid lactones to aldose sugars also may be accomplished by catalytic hydrogenation (I40) or, very conveniently, with sodium borohydride in aqueous solution ) Other methods of reduction include the catalytic hydrogenation of the acetylated aldonyl chlorides (14 ) or thio esters (I4S). 

One would expect aldoses to combine the chemistries of alcohols and aldehydes, and that expectation is correct. In fact, the proximity of these functional groups leads to important intramolecular chemistry, and here is an example. Although reduction of glucose with sodium borohydride followed by hydrolysis induces the expected change (see Problem 22.6), modern spectroscopic methods such as NMR and IR do not reveal the presence of substantial amounts of the aldehyde in the starting carbohydrate (Fig. 22.10). It is important to understand why this is so. The chemistry of the aldose tells us there is an aldehyde and we certainly have been drawing an aldehyde group in our Rscher projections. So why cant we observe the aldehyde spectroscopically ... 

The first two entries in Table 23.2 illustrate reactions that involve nucleophilic addition to the carbonyl group of the open-chain form which, although present in small amounts, is continuously replenished as it reacts. Entry 1 is the sodium borohydride reduction of the carbonyl group of the aldose o-galactose. The reaction is a general one other... 

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