Synthesis of Higher Sugars

The addition of cyanide to simple aldoses is essentially quantitative in solutions buffered at pH 9.1 increased acidity causes diminished reaction rates. The reaction can be conveniently effected using a solution of sodium cyanide and calcium chloride, but varied conditions may be required in order to obtain desired proportions of the epimeric products. The latter arise from the creation of a new asymmetric center, and are generally not produced in equal amoimts because of the asymmetric nature of syntheses using optically active starting materials. The epimeric preference may be so high as to give essentially quantitative yields of one product. For ex- 

Fractionation is achieved after conversion of the epimeric nitriles to acids by hydrolysis. The method selected is usually specific for the particular acids involved and may be based on fractional recrystallization of lactones, alkali or other metal salts, phenylhydrazides, or other suitable derivatives. 

In theory, all the higher aldoses are available by cyanohydrin synthesis, but, in practice, the successful preparation of a particular aldose depends on the formation of its intermediate cyanohydrin in reasonable 3deld at each individual cyanide addition. However, by using varied reaction conditions, such as those investigated with n-arabinose, it may well be possible to obtain higher sugars hitherto inaccessible because their precursor cyanohydrins were not preferred epimers. 

This method for the synthesis of higher-carbon ketoses is based on the reaction of diazomethane with an acid chloride to give a diazomethyl ketone which, on hydrolysis (or acetolysis), furnishes a hydroxy (or acetoxy) methyl ketone. The reaction was first applied in the sugar field in 1938 and has since been widely used in the synthesis of ketoses by Wolfrom and coworkers. As developed by Wolfrom, the synthesis uses fully acety-lated derivatives in the following stages aldose — acetylated aldonic acid acetylated aldonyl chloride acetylated diazomethyl ketose — acetylated ketose — ketose. The method is illustrated in the synthesis of D-galacto-heptulose (10).  

Although the individual reactions of the synthesis all proceed in satisfactory yield, the relatively large number of consecutive stages results in a 

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Scheme 8.32 Kiliani-Fischer synthesis of higher sugars.

The cyanohydrin synthesis of higher sugars, which involves intermediate aldonolactones, allows the introduction of a 14C label in the sugar chain. Thus, for example, L-[5-l4C]arabinose was synthesized (12) from D-xylose, which was first converted, by addition of K14CN and hydrolysis, into D-[ 1-... 

S. Jarosz and B. Fraser-Reid, Synthesis of higher sugars via allytltin derivatives of simple monosaccharides, J. Org. Chem. 54 4011 (1989). 

An important transformation of dialdoses is the chain extension to homologous products by condensations performed on the aldehyde group. When asymmetric induction occurs, this transformation is extremely valuable for the stereocontrolled synthesis of higher sugars. 

N. K. Kochetkov and B. A. Dmitriev, Application of the Wittig reaction to the synthesis of higher sugars, Methods Carbohydr. Chem., 6 (1972) 150-153. 

The process yields an interesting synthon for the synthesis of higher sugars with complete stereocontrol. Higher sugars play important roles in many biological processes. Prominent examples are KDO (3-deoxy-D-manno-octulosonic acid), a component of bacterial liposaccharides [37], and iV-acetylneuraminic acid, which is a crucial component of human and animal glycoconjugates [38,39]. In addition, derivatives of iV-acetylneuraminic acid show remarkable antiviral properties [40]. 

The triflates catalyse the allylation of carbonyl compounds with tetraallyltin, producing intermediates in the synthesis of higher sugars. 

The diastereoselective synthesis of higher sugars was accomplished by bZi-osmylation of sugar derived dienes using OsO4-NMO4°. As shown in equation 23, osmylation of diene 26 afforded diastereomeric sugars 27, 28, and 29 in 90% overall yield in a 6.6 1.2 1.0 ratio, respectively. 

Narkunan, K., and Nagarajan, M., Preparation of sugar-derived P-keto phosphonates and their use in the synthesis of higher sugars, J. Org. Chem., 59, 6386, 1994. 

Methods for the synthesis of higher sugars generally involve chain-ascent procedures from lower aldoses. 

Acyclic Alditols. - Brimacombe s group have published full details of their work on the stereoselective synthesis of higher sugars, some of which is covered in Chapter 2 other papers describe the Sharpless oxidation of the octose derivative (1) to give the oxiran (2), and hence the D-erythro isomer (3), osmylation... 

FIGURE 10.16 Synthesis of higher sugar enones hy reaction of sngar aldehydes with stabilized sugar ylids or sugar phosphonates. 

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