Kiliani–Fischer synthesis

The Kiliani -Fischer synthesis ( also cyanohydrin synthesis) is used to extend the carbon chain of sugars, such as in the reaction of an aldopentose to aldohexose. Named are Henry Kiliani and Emil Fischer.

Classic pathway

The major pathway that has been proposed by examination of the intermediates in the course of the reaction, provides for D- arabinose, D- Hexononitril → ( a cyanohydrin ) → D → D Hexonoimidolacton Hexonolacton → D- hexonic acid.

First, it comes to nucleophiles addition of hydrocyanic acid (HCN ) to the carbonyl group of the aldose, here D -arabinose 1 Since the attack can be carried out on the carbon from two sides, this form two diastereomeric cyanohydrins, in this case 2 - D and Mannonsäurenitril 2b D- Gluconsäurenitril.

Then it comes to the hydrolysis of the nitrile to the carboxylic acid. This is initially by a nucleophilic addition of water to the triple bond, then a rearrangement, and finally a nucleophilic substitution, since the amino group is replaced by a hydroxy group. This results in two diastereomeric Aldonate: 3a and 3b Mannonat D- D- gluconate.

In the acidic environment it comes to spontaneous cyclodehydration to five-membered ring lactones ( γ - lactones ): 4a γ -D - mannonolactone and 4b γ -D - gluconolactone.

The last step is the reduction of the carboxylic acid with sodium amalgam, to give the aldehyde. Here, the sodium amalgam is oxidized to Natriumamalgamoxid and it ultimately results in two epimeric aldo: 5a and 5b D-Mannose D -glucose.

Modern developments

1958 described R. Kuhn et al. a method which allows a higher yield particularly for longer sugars such as glucose or mannose. Instead of the implementation of the cyanohydrin to the lactam this is converted by reductive hydrogenation to Pd/BaSO4 in water as a solvent to form the imine. This in turn hydrolyzed under the conditions given immediately to the aldehyde. The use of poisoned catalysts, such as Lindlar catalysts, is necessary to prevent the complete reduction to the alcohol.

The example illustrates the chain extension of L- threose to L- xylose and L- lyxose.