Kiliani

An older version of this sequence is called the Kiliani-Fischer synthesis It too proceeds through a cyanohydrin but it uses a less efficient method for converting the cyano group to the required aldehyde... 

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... 

Addition of hydrogen cyanide to an aldose to form a cyanohydrin is the first step in the Kiliani-Fischer method for increasing the carbon chain of aldoses by one unit. Cyanohydrins react with Grignard reagents (see Grignard reaction) to give a-hydroxy ketones. 

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. 

Heinrich Kiliani (1855-1945) was born in Wiirzburg. Germany, and received a Ph.D. at the University of Munich with Emil Erlenmeyer. He was professor of chemistry at the University of Freiburg, where he worked on the chemistry of the heart stimulant drug digitoxin. 

Discovery of the chain-lengthening sequence was initiated by the observation of Heinrich Kiliani in 1886 that aldoses react with HCN to form cyanohydrins (Section 19.6). Emil Fischer immediately realized the importance of Kiliani s discovery and devised a method for converting the cyanohydrin nitrile group into an aldehyde. 

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. 

Problem 25.21 1 What product(s) would you expect from Kiliani-Fischer reaction of n-ribose ... 

Problem 25.22 What aldopentose would give a mixture of L-gulose and L-idose on Kiliani-Fischer chain extension ... 

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. 

Much of the chemistry of monosaccharides is the familiar chemistry of alcohols and aldehydes/ketones. Thus, the hydroxyl groups of carbohydrates form esters and ethers. The carbonyl group of a monosaccharide can be reduced with NaBH4 to form an alditol, oxidized with aqueous Br2 to form an aldonic acid, oxidized with HNO3 to form an aldaric acid, oxidized enzymatically to form a uronic acid, or treated with an alcohol in the presence of acid to form a glycoside. Monosaccharides can also be chain-lengthened by the multistep Kiliani-Fischer synthesis and can be chain-shortened by the Wohl degradation. 

Compound A is a D aldopentose that can be oxidized to an optically inactive aldaric acid B. On Kiliani-Fischei chain extension, A is converted into C and D C can be oxidized to an optically active aldaric acid E, but D is oxidized to an optically inactive aldaric acid F. What are the structures of A-F ... 

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

Arabinose, configuration of. 982 Kiliani-Fischer synthesis on. 995 Arachidic acid, structure of, 1062 Arachidonic acid, eicosanoids from, 1069-1070... 

Keto-enol tautomerism, 264, 842-844 Kiliani, Heinrich, 994 Kiliani-Fischer synthesis, 994-995 Kimbail, George, 216 Kinetic control, 491 Kinetics, 362... 

With the same synthetic sequence, labeled ribose molecules produced AIRs labeled on the ribose moiety. From D-erythrose and (l3C)NaCN, the Fischer-Kiliani synthesis, as modernized by Serianni et al.59 produced D-(l-l3C)ribose and D-(l-l3C)arabinose. The labeled arabinose was transformed into D-(2-l3C)ri-bose in the presence of dioxobis(2,4-pentanedionato)-0-0 -molybdenum(VI) in... 

Frequently, it is the bisulfite addition product that is treated with CN. This method is especially useful for aromatic aldehydes, since it avoids competition from the benzoin condensation. If desired, it is possible to hydrolyze the cyanohydrin in situ to the corresponding a-hydroxy acid. This reaction is important in the Kiliani-Fischer method of extending the carbon chain of a sugar. 

Scheme 8.32 Kiliani-Fischer synthesis of higher sugars.

The carbon-chain structure of the sugar obtained from hamameli-tannin was established by the classical method of Kiliani,26 which is based on the reduction, with hydrogen iodide, of polyhydroxy acids to fatty acids. Treatment of the calcium salt of hamamelonic acid under these conditions led to inconclusive results. The reduction of the corresponding, crystalline ammonium salt, however, furnished 3.5 to 5% of 2-methylvaleric acid, which was identified by the properties of its crystalline p-iodophenacyl ester. Thus, it was proved that the sugar must have structure XIV. 

The extension of the salt-acid,27 phenylhydrazide,28 and amide rules29 to the derivatives of the 2-(hydroxymethyl) sugars by Schmidt and Weber-Molster30 indicated that the configuration of C2 in hamamelonic acid is the same as that of D-ribonic acid. Finally, the d-ribo configuration of the sugar was established by the synthesis of hamamelonic acid and its C2 epimer from D-ery/ftro-pentulose31 by the cyanohydrin reaction of Fischer and Kiliani. 

In an attempt to synthesize 2-desoxy-L-ribose, Mukherjee and Todd68 treated methyl 2,3-anhydro-jS-L-ribopyranoside (LXXII) with sodium thiomethoxide and then reduced the amorphous product. The sulfur-free sirup thus obtained was inert to the action of periodate and is therefore methyl 3-desoxy-/3-L-riboside (ayn., methyl 3-desoxy-/3-L-xyloside) (LXXIV) rather than the desired 2-desoxy derivative. The methylthio intermediate (LXXIII) was consequently a 3-methylthio-L-xylose derivative rather than a 2-methylthio-L-arabinose compound. The presence of a trace of the latter, however, is not wholly excluded since the sirupy desoxypentoside (LXXIV) gave a feeble green coloration in the Keller-Kiliani test, a reaction generally accepted as being specific for 2-desoxy-sugars. 

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