Kiliani—Fischer synthesis

An older version of this sequence is called the Kiliani-Fischer synthesis It too proceeds through a cyanohydrin but it uses a less efficient method for converting the cyano group to the required aldehyde... 

The Kiliani-Fischer synthesis pro ceeds by nucleophilic addition of HCN to an aldose followed by con version of the cyano group to an al dehyde A mixture of stereoisomers results the two aldoses are epi meric at C 2 Section 25 20 de scribes the modern version of the Kiliani-Fischer synthesis The example at the right illus trates the classical version... 

Kiliani-Fischer synthesis (Section 25.20) A synthetic method for carbohydrate chain extension. The new carbon-carbon bond is formed by converting an aldose to its cyanohydrin. Reduction of the cyano group to an aldehyde function completes the synthesis. 

Fischer s original method for conversion of the nitrile into an aldehyde involved hydrolysis to a carboxylic acid, ring closure to a cyclic ester (lactone), and subsequent reduction. A modern improvement is to reduce the nitrile over a palladium catalyst, yielding an imine intermediate that is hydrolyzed to an aldehyde. Note that the cyanohydrin is formed as a mixture of stereoisomers at the new chirality center, so two new aldoses, differing only in their stereochemistry at C2, Tesult from Kiliani-Fischer synthesis. Chain extension of D-arabinose, for example, yields a mixture of D-glucose and o-mannose. 

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. 

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. 

Kiliani-Fischer synthesis (Section 25.6) A method for lengthening the chain of an aldose sugar. 

Arabinose, configuration of. 982 Kiliani-Fischer synthesis on. 995 Arachidic acid, structure of, 1062 Arachidonic acid, eicosanoids from, 1069-1070... 

Keto-enol tautomerism, 264, 842-844 Kiliani, Heinrich, 994 Kiliani-Fischer synthesis, 994-995 Kimbail, George, 216 Kinetic control, 491 Kinetics, 362... 

Scheme 8.32 Kiliani-Fischer synthesis of higher sugars.

A sequence known as the Kiliani-Fischer synthesis was developed primarily for extending an aldose chain by one carbon, and was one way in which configurational relationships between different sugars could be established. A major application of this sequence nowadays is to employ it for the synthesis of " C-labelled sugars, which in turn may be used to explore the role of sugars in metabolic reactions. 

Kiliani-Fischer synthesis is a means of lengthening the carbon backbone of a carbohydrate. The process begins with the reaction of hydrogen cyanide (HCN) with an aldehyde to produce a cyanohydrin. Treatment of the cyanohydrin with barium hydroxide followed by acidification yields an aldose with an additional carbon atom, as shown in Figure 16-16. The formation of the cyanohydrin creates a new chiral center as a racemic mixture. 

Figure 16-17 shows a specific example of Kiliani-Fischer synthesis. 

Problem 22.18 Write shorthand formulas for the tetroses prepared from (a) L-glycerose, (b) o-glycerose, by the Kiliani-Fischer synthesis. -4... 

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. 

Which of the following pentoses, when undergoing the Kiliani-Fischer synthesis, will yield D-glucose and D-mannose ... 

D-(+)-glyccraldchyde was allowed to undergo the Kiliani-Fischer synthesis. and the reaction ran to completion. After separation of any isomers, how many optically active products were formed ... 

Figure 7.15 displays the classic Kiliani-Fischer synthesis, a three-step reaction sequence for the homologation of aldoses. You can see the Cj -lengthening of D-arabinose to produce D-glu-cose and D-mannose. 

In the first step of the Kiliani-Fischer synthesis, HCN adds to the C=0 double bond of the tetrahydroxy aldehyde, which is in equilibrium with the predominant hemiacetal form of ara-... 

The duration of the reaction time alone determines whether carbonyl compounds, sodium cyanide and ammonium chloride will generate a cyanohydrin (Figure 9.9, top) or an a-aminonitrile (Figure 9.9, bottom). We are already familiar with the first reaction pattern from the initial reaction of the three-step Kiliani-Fischer synthesis of aldoses (Figure 7.15). The second reaction pattern initiates the Strecker synthesis of a-amino acids, which is completed by a total hydrolysis of the C=N group, as in the Bucherer modification discussed elsewhere (Figure 7.11). 

The behavior of ribose in the Kiliani-Fischer synthesis has recently... 

The final reaction to be covered in this section is known as the Kiliani-Fischer synthesis. It is a method that converts an aldose to two diastereomeric aldoses that contain one more carbon than the original sugar. The Kiliani-Fischer synthesis is illustrated in the following reaction sequence, which shows the formation of the aldopentoses D-ribose and D-arabinose from the aldotetrose D-erythrose ... 

---