Kiliani–Fischer synthesis

Kiliani–Fischer synthesis is a chemical reaction that serves as a method for elongating the carbon chain of aldose sugars by one carbon atom. This synthesis, named after the German chemists Heinrich Kiliani and Emil Fischer, is a pivotal reaction in the field of carbohydrate chemistry. It involves the addition of a cyanide ion to the carbonyl group of an aldose, followed by hydrolysis and stereospecific reduction, ultimately yielding a pair of epimeric aldoses, each extended by one carbon atom.

Process

The Kiliani–Fischer synthesis begins with the nucleophilic addition of cyanide to the carbonyl group of an aldose, forming a cyanohydrin. This step is critical as it introduces the new carbon atom. The cyanohydrin is then hydrolyzed under acidic conditions to form an intermediate dicarboxylic acid, which upon subsequent reduction (typically using hydrogenation over a catalyst or chemical reducing agents) yields two epimers of the original aldose, each extended by one carbon atom. The process exploits the chiral nature of the aldose starting material, leading to the formation of stereoisomers at the newly created chiral center.

Significance

The Kiliani–Fischer synthesis has been instrumental in the structural elucidation and synthesis of carbohydrates. Before the advent of modern spectroscopic techniques, it was one of the few methods available for determining the relative configuration of sugars and for synthesizing larger sugars from smaller ones. This method has allowed chemists to systematically synthesize a wide array of sugars, including those that are rare in nature, and to study their properties and biological activities.

Limitations

While the Kiliani–Fischer synthesis is a powerful tool in carbohydrate chemistry, it has limitations. The method introduces a new chiral center, leading to a mixture of epimers that must be separated, often requiring additional steps. Furthermore, the reaction conditions can sometimes lead to the destruction of sensitive functional groups in the sugar molecule.

Applications

Despite its limitations, the Kiliani–Fischer synthesis remains a fundamental reaction in the synthesis of complex carbohydrates and oligosaccharides. It is used in the synthesis of rare sugars, in the modification of naturally occurring sugars for the study of their biological functions, and in the preparation of sugar derivatives for pharmaceutical applications.

See Also

• Carbohydrate chemistry
• Stereospecificity
• Nucleophilic addition
• Cyanohydrin reaction