Kiliani–Fischer synthesis

The Kiliani–Fischer synthesis, named for

monosaccharides. It proceeds via synthesis and hydrolysis of a cyanohydrin, followed by reduction of the intermediate acid to the aldehyde, thus elongating the carbon chain of an aldose by one carbon atom while preserving stereochemistry on all the previously present chiral carbons. The new chiral carbon is produced with both stereochemistries, so the product of a Kiliani–Fischer synthesis is a mixture of two diastereomeric sugars, called epimers. For example, D-arabinose is converted to a mixture of D-glucose and D-mannose

.

Classic Kiliani–Fischer synthesis

The original version of the Kiliani–Fischer synthesis proceeds through

chemical yield

by this method is estimated to be around 30%.

D-arabinose

Improved version

More recently, an improved reduction method has been developed that produces somewhat higher yields of the larger sugars. Instead of conversion of the cyanohydrin to a lactone, the cyanohydrin is

catalyst and water as the solvent, to form an imine

. Due to the presence of water, the imine quickly hydrolyzes to form an aldehyde, thus the final sugars are produced in just two steps rather than three. The separation of the isomers is then performed at the stage of the sugar products themselves rather than at the lactone intermediates. The special catalyst is needed to avoid further reduction of the

Lindlar palladium

is another example. The reactions below illustrate this improved method for the conversion of L-threose to L-lyxose and L-xylose.

An improved version of the Kiliani–Fischer synthesis

Uses and limitations

Both enantiomers of glyceraldehyde are commercially available, so one can access any stereoisomer of any chain-length aldose by an appropriate number of repeated applications of the Kiliani–Fischer synthesis. The triose D-glyceraldehyde (1) leads to the tetroses D-erythrose (2a) and D-threose (2b). Those lead to the pentoses D-ribose (3a) and D-arabinose (3b), and D-xylose (3c) and D-lyxose (3d), respectively. The next iteration leads to the hexoses D-allose (4a) and D-altrose (4b), D-glucose (4c) and D-mannose (4d), D-gulose (4e) and D-idose (4f), and D-galactose (4g) and D-talose (4h). The D-heptoses and beyond are available by continuing the sequence, and enantiomeric L series is available by starting the sequence with L-glyceraldehyde.

In practice, the Kiliani–Fischer synthesis is usually used for production of sugars that are difficult or impossible to obtain from natural sources. While it does provide access to every possible stereoisomer of any desired aldose, the process is limited by its low yield and use of toxic reagents. In addition, the process requires having a supply of the previous sugar in the series, which may itself require substantial synthetic work if it is not readily available. For example, if successive iterations of the Kiliani–Fischer synthesis are used, the overall yield drops approximately exponentially for each additional iteration.

The process only provides direct access to aldoses, whereas some sugars of interest may instead be ketoses. Some ketoses may be accessible from similar aldoses by isomerization via an

aldol addition

.

References

Carey, Francis A. (2006). Organic Chemistry, Sixth Edition, New York, NY: McGraw-Hill.
ISBN 0-07-111562-5
.

Classic Kiliani–Fischer synthesis

Improved version

Uses and limitations

See also

References