Aldoses Kiliani-Fischer synthesis

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. 

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

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. 

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. 

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. 

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 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 ... 

The Kiliani-Fischer synthesis accomplishes the opposite of the Ruff degradation. Ruff degradation of either of two C2 epimers gives the same shortened aldose, and the... 

Kiliani-Fischer synthesis converts this shortened aldose back into a mixture of the same two C2 epimers. For example, glucose and mannose both undergo Ruff degradation to give arabinose. Conversely, the Kiliani-Fischer synthesis converts arabinose into a mixture of glucose and mannose. 

A method for elongating an aldose at the aldehyde end. The aldose is converted into two epimeric aldoses with an additional carbon atom. For example, Kiliani-Fischer synthesis converts D-arabinose to a mixture of D-glucose and D-mannose. (p. 1125)... 

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 adds a carbon to the aldehyde end of an aldose, forming two epimers at C2. 

What aldoses are formed when the following aldoses are subjected to the Kiliani-Fischer synthesis (a) D-threose (b) D-ribose (c) D-galactose ... 

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

Since a six-carbon aldonic acid contains —OH groups in the y- and 8-posi-tions, we would expect it to form a lactone under acidic conditions (Sec. 20.15). This occurs, the y-lactone generally being the more stable product. It is the lactone that is actually reduced to an aldose in the last step of a Kiliani-Fischer synthesis. 

The pair of aldoses obtained from the sequence differ only in configuration about C 2, and hence are epimers. A pair of aldoses can be recognized as epimers not only by tbeir conversion into the same osazone (Sec. 34.7), but also by their formation in the same Kiliani-Fischer synthesis. 

---