Higher carbon aldoses

In 1991, Whitesides etal. reported the first application of aqueous medium Barbier-Grignard reaction to carbohydrate synthesis through the use of tin in an aqueous/organic solvent mixture (Eq. 8.48).106 These adducts were converted to higher carbon aldoses by ozonolysis of the deprotected polyols followed by suitable derivatization. The reaction showed a higher diastereoselectivity when there was a hydroxyl group present at C-2. However, no reaction was observed under the reaction conditions when there was an /V-acctyl group present at the C-2 position. 

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... 

It will be noted that not only are higher-carbon aldose sugars and ketose sugars available through the nitromethane and 2-nitroethanol... 

The sodium deoxynitroalditols are readily decomposed with dilute sulfuric acid to give the corresponding higher-carbon aldose sugars, which... 

The nitromethane synthesis of higher-carbon aldose sugars utilizes two well-known general reactions of the nitroparaflBns. These are the base-catalyzed condensation of nitromethane with an aldehyde to produce a C-ni-troalcohol (146), and the decomposition of the sodium salt of the latter with cold, moderately concentrated mineral acid to produce an aldehyde (147) containing one more carbon atom than the original aldehyde. 

In 1921 Pictet and Barbier28 recorded an attempt to produce higher-carbon sugar alcohols from aldose sugars by means of the reaction sequence ... 

Thus, the 2-nitroethanol synthesis results in the addition of two carbon atoms to an aldose sugar to produce two higher-carbon ketose sugars epimeric at carbon 3. While the synthesis is general in nature, the two ketoses produced from any one aldose are seldom as readily separable as is fortunately the case with D-mannoheptulose and D-gluco-heptulose. However, the newly developed techniques of adsorption and partition chromatography will undoubtedly be of service for the more difficult separations. 

First, let us look at a method for converting an aldose into another aldose containing one more carbon atom, that is, at a method for lengthening the carbon chain. In 1886, Heinrich Kiliani (at the Technische Hochschule in Munich) showed that an aldose can be converted into two aldonic acids of the next higher carbon number by addition of HCN and hydrolysis of the resulting cyanohydrins. In 1890, Fischer reported that reduction of an aldonic acid (in the form of its lactone. Sec. 20.15) can be controlled to yield the corresponding aldose. In Fig. 34.2, the entire Kiliani-Ffscher synthesis is illustrated for the conversion of an aldopentose into two aldohexoses. 

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). ... 

A method of degradation with excellent preparative possibilities has been devised by MacDonald and Fischer (200), The higher-carbon sugar first is condensed with ethyl mercaptan to form the bis(ethylthio)acetal (mercaptal) (I) (Chapter IV). Oxidation of the mercaptal with perpro-pionic acid then leads to the bis(ethylsulfonyl) compound (II), which is smoothly degraded by aqueous ammonia to the next lower aldose and bis(ethylsulfonyl)methane. 

When applied to carbohydrates, the sono-allylation proceeded with useful diastereoselectivity (rAreo-selectivity) and allowed preparation of higher-carbon sugars from water-soluble substrates directly in aqueous ethanol without protection (Schmid and Whitesides, 1991). Later, the authors showed that the allylation of aldoses could be advantageously carried out by heating the reaction mixture for example, the allylation of D-arabinose required 16-20h under sonication, but only 2h under reflux (Kim et al., 1993) ... 

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