Chain Lengthening The Kiliani-Fischer Synthesis

Chain lengthening. The Kiliani-Fischer synthesis adds a new C(l) aldehyde and generates a pair of C(2) stereoisomers (Fig. 22.20). 

Just as the Kiliani-Fischer synthesis lengthens an aldose chain by one carbon, the Wohl degradation shortens an aldose chain by one carbon. The Wohl degradation is almost the exact opposite of the Kiliani-Fischer sequence. That is, the aldose aldehyde carbonyl group is first converted into a nitrile, and the resulting cyanohydrin loses HCN under basic conditions—the reverse of a nucleophilic addition reaction. 

The Kiliani-Fischer synthesis lengthens the carbon chain of an aldose by one carbon at the aldehyde end and forms a new aldose with its corresponding epimers. When glucose and its epimer are produced from the corresponding pentose via the Kiliani-Fischer synthesis, and then both epimers are reacted with dilute nitric acid, both form optically active compounds. 

Two common procedures in carbohydrate chemistry result in adding or removing one carbon atom from the skeleton of an aldose. The Wohl degradation shortens an aldose chain by one carbon, whereas the Kiliani-Fischer synthesis lengthens it by one. Both reactions involve cyanohydrins as intermediates. Recall from Section 21.9 that cyanohydrins are formed from aldehydes by addition of the elements of HCN. Cyanohydrins can also be re converted to carbonyl compounds by treatment with base. 

The Kiliani-Fischer synthesis lengthens a carbohydrate chain hy adding one carhon to the aldehyde end of an aldose, thus forming a new stereogenic center at C2 of the product. The product consists of epimers that differ only in their configuration about the one new stereogenic center. For example, the Kiliani-Fischer synthesis converts D-arabinose into a mixture of D-glucose and D-mannose. 

Lengthening the carbon chain of aldoses. The Kiliani-Fischer synthesis... 

Cyanohydrins derived from aldehydes are generally more stable than those from ketones (Ternay, 1976). Cyanohydrin formation is the first step in the well-known chain-lengthening sequence, the Kiliani-Fischer synthesis. For example, D-arabinose, an aldopentose, ultimately affords both o-glucose and D-mannose by this set of reactions (Carey, 2000b). 

In 1885, Heinrich Kiliani (Freiburg, Germany) discovered that an aldose can be converted to the epimeric aldonic adds having one additional carbon through the addition of hydrogen cyanide and subsequent hydrolysis of the epimeric cyanohydrins. Fischer later extended this method by showing that aldonolactones obtained from the aldonic acids can be reduced to aldoses. Today, this method for lengthening the carbon chain of an aldose is called the Kiliani-Fischer synthesis. 

Just as the Kiliani—Fischer synthesis can be used to lengthen the chain of an aldose by one carbon atom, the Ruff degradation can be used to shorten the chain by a similar unit. The Ruff degradation involves (1) oxidation of the aldose to an aldonic acid using bromine water and (2) oxidative decarboxylation of the aldonic acid to the next lower aldose using hydrogen peroxide and ferric sulfate. d-(—)-Ribose, for example, can be degraded to D-(—)-erythrose ... 

The Kiliani-Fischer synthesis can be used to lengthen the chain of an aldose. 

In this hydrogenation, a modified palladium catalyst (similar to the Lindlar catalyst. Section 13-6) allows selective reduction of the nitrile to the imine, which hydrolyzes under the reaction conditions. The special catalyst is necessary to prevent the hydrogenation from proceeding all the way to the amine (Section 20-8). The preceding chain-lengthening sequence is an improved and shortened version of what is known as the Kiliani-Fischer synthesis of... 

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. 

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