Kiliani reaction

Cyanide ions react with aldehydes and ketones to yield cyanohydrins (Kiliani) (Fig. 2-28). Hydrolysis of the cyanohydrins gives aldonic acids, which can be reduced to aldoses. Kiliani reaction thus opens the possibility for chain lengthening of aldoses. Because of the formation, of a hydroxyl group in place of the aldehyde group a new asymmetric center is generated. It is to be observed, however, that the reaction is subject to so-called asymmetric induction, which means that the diastereoisomers are formed in unequal proportions. 

Fig. 2-28. Kiliani reaction. Addition of hydrogen cyanide to D-arabinose (1) yields cyanohydrins (2) and (3), which are hydrolyzed to D-gluconic acid (4) and D-mannonic acid (5). Because of asymmetric induction preferentially (4) is formed.

Figure 1.4 General outline of the varions versions of the Kiliani reaction. PG=protecting group.

Extension of the carbon chain of an aldose from the carbonyl by one unit at a time can be carried out fairly readily by the Kiliani reaction. A cyanhydrin is formed by addition of cyanide ion, followed by reduction and hydrolysis (in either order) historically, the sugar was unprotected, and the cyanohydrin was hydrolysed to the sugar lactone, and then reduced with sodium amalgam (Figure 1.4). Because a new asymmetric centre is formed, two epimeric sugars result (epimers are diastereomers that differ in the configuration of only one carbon). 

Structures of the pentoses. Whilst the aldopentoses can in practice be derived from the aldotetroses by the Kiliani reaction, no such simple route... 

Figure 1.6 sets out the structures of the aldohexoses and the aldopentoses from which they can be derived by the Kiliani reaction. Aldohexoses have four non-equivalent asymmetric centres, and hence there are 16 (2" ) stereoisomers, 8 pairs of enantiomers. 

The Kiliani reaction with finctosamine and other ketosamines may provide an access to a-polyhydroxyalkyl-P-amino acids,for use as chiral metal chelators or building blocks for glyco- and peptido-mimetics. 

A part of the specimen N-93 was extracted with chloroform, and a glycoside fi action (S-chf) was obtained. The residue was extracted with methanol. For the reference, the chloroform extracts of the roots of C. caudatum and C. wilfordii were prepared and named A-chf and B-chf, respectively. All the chloroform extracts, S-chf, A-chf and B-chf, gave positive Keller-Kiliani reaction and Liebermann-Burchard reaction, showing the presence of 2,6-dideoxysugar and steroidal skeleton in their structures, respectively. However, the HPTLC pattern of S-chf on a silica gel plate developed by CHCl3-Me0H-H20 (65 35 10, lower layer) was different fi om those of A-chf and B-chf (Fig. 1)... 

A Kiliani reaction of L-erythrose with labelled cyanide was... 

The Kiliani reaction with D-arabinose using [ cyanide and [ cyanide... 

The first discussions concerning the conditions for aeating optically active compounds in the laboratory may be traced to Pasteur and Le Bel. The first mention of the expression "asymmetric synthesis" can be found in the work of E. Fischer in 1894 concerning his stereochemical studies on sugars. He observed the formation of unequal amounts of cyanohydrins in the Kiliani reaction applied to aldehydic sugars. In 1904, Marckwald reported an asymmetric synthesis of 2-methyl-butanoic acid by decarboxylation of 2-ethyl 2-methyl-malonic acid in the presence of an alkaloid. The importance and the mechanism of this reaction were later the subject of much debate. However, this paper remains significant because Marckwald defined asymmetric synthesis, as follows "It is a reaction giving optically active products from symmetrical... 

In many cases the homologation steps represented by arrows on page Cl have been realised in practice, by sequences such as R-CHO - RCH(OH)CN - RCH(OH)CHO (Fischer-Kiliani reaction) but even in cases where they have not, the configurations of the individual monosaccharides are supported by a wealth of other evidence [ 1 ] [2]. 

The four nucleosides of RNA have been prepared with 13C labels at either C-1 or C-2, for use in nmr studies,by condensation with an appropriately-labelled D-ribose derivative. Label at C-1 was introduced by a Kiliani reaction, and at C-2 by molybdate-catalysed rearrangement of 1-13C-... 

Addition of Cyanide-The Kiliani Reaction Probably the earliest method for the construction of heptoses consisted of the addition of one-carbon nucleophiles such as nitromethane and cyanide on the anomeric aldehyde of hexoses. Indeed, heptonic acids are readily available from the Kiliani reaction of hexoses as depicted in Scheme 2.17 [42]. 

The Kiliani reaction is amenable on a large scale, leading to y- or 8-heptonolactones depending on the reaction conditions. The latter can further be protected and derivatized to give a wide range of chiral synthons. 

Beyond the synthesis of heptosylated natural molecules, artificial heptosides have been designed and synthesized to address different biochemical problems such as the search of virulence factors [60]. As detailed above, the Kiliani reaction has allowed the synthesis of iminoheptitols, a validated class of glycosidase inhibitors... 

Digoxin is a crystalline glycoside obtained from Digitalis lanata and no assay is required in the standard of the B.P, For the injection and tablets, however, application is made of the Keller-Kiliani reaction. The U.S,P, assays Digoxin by an application of the w-nitrobenzene reaction and a similar method, based on the work of Honk et al. has been adopted by the A.O.A.C, For the assay of digoxin injection and tablets the IJ.S.P. also uses the Keller-Kiliani method. Suitable examples of the m-dinitrobenzene and Keller-Kiliani methods are given below ... 

Carrying out the Kiliani reaction using H CN on the dialdose derivative (12) followed by hydrolysis to the labelled alduronic acid, reduction to the alcohol and hydrolysis with trifluoroacetic... 

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