Kiliani-fischer Synthesis of Monosaccharides

Kiliani-fischer Synthesis of MonosaccharidesTeoh Shi Hao SeanIntroductionMonosaccharides are the intimately basic unit of carbohydrates, playing an essential role in the biochemistry of life. The roughly important and commonly occurring form is glucose, used as an energy antecedent in cells (Solomon et al., 2011). Monosaccharides have the chemical formula (C body of water)n (where n 3) exactly those with eight-spot or more carbons are uncommon due to their inherent mental unsoundness (Solomon et al., 2011 McMurry, 2008). In a simple sugar soupcon, each carbon atom has a hydroxyl gathering bonded to it, except one which has an oxygen atom double bonded to it instead thus forming a carbonylic assembly (Solomon et al., 2011). The monosaccharide is an aldehyde if the carbonyl assort is located at the windup of the chain, and a ketone if the carbonyl group is located at any other position. Monosaccharides can exist in acyclic or cyclic forms, and usually switch between the devil forms (McMurry, 2008). The Kiliani-Fischer discount is a proficiency for leng henceing these important biomolecules.Mechanism physique 1 below shows the reaction equivalence of the technique. A starting mark is first reacted with sodium cyanide to form cyanohydrin, and accompanyingly hydrolysed through the masking of heat to form two diastereomeric aldonic panelling lactone ordinarys. These mediates are later apart(p) through separation techniques, such as chromatography, and the desired lactone is reduced apply a sodium dental amalgam to form a resultant stops that has one carbon atom more than the starting wampumpeag. In this indite review, the starting loot will be a aldopentose and the resultant sugar will be a aldohexose. get into 1 Reaction equation of the Kiliani-Fischer implication (Kilini-Fischer synthesis, 2014 Fischer, 1890).Nucleophilic addition of aldehyde to form cyanohydrinThe first step in Kiliani-Fischer synthesis involves nucleophilic additio n of the starting sugar, an aldehyde. NaCN and urine are used as reagents (McMurry, 2008). protrude 2 below shows the instrument of the reaction. A solitary pair on a CN ion initiates the reaction by attacking the nucleophilic carbon atom at the carbonyl group, forming a tetrahedral intermediate. The O then attacks the H atom of a H2O molecule, forming a cyanohydrin. finger 2 Reaction of starting sugar to form cyanohydrin.Hydrolysis of cyanohydrin to form aldonic mordantThe flash step in Kiliani-Fischer synthesis involves the hydrolysis of the cyanohydrin to form aldonic acid (McMurry, 2008). H2O is used as the reagent, with heat applied. Figure 3 below shows the mechanism of the reaction. The alone(predicate) pair on the O of OH, formed by the auto-ionization of water, attacks the nucleophilic C of the cyanohydrin forming a trigonal planar social system. The lone pair on the N then attacks an H of a H2O molecule, followed by the double bond of C=N attacking the H atom bonde d to the OH group. The resultant molecule is an amide. An OH ion then attacks the nucleophilic carbon at the carbonyl group, forming a tetrahedral intermediate that collapses with NH2 leaving as a leaving group. An aldonic acid molecule is formed.Figure 3 Hydrolysis of cyanohydrin to form aldonic acid.Esterification of aldonic acid to form lactone intermediate and subsequent reduction to form resultant sugarWith the same reagent of H2O and conditions of heat, the aldonic acid produced from the hydrolysis of cyanohydrin undergoes esterification to form lactone intermediates (McMurry, 2008). Figure 4 below shows the mechanism of the reaction. A lone pair on the O at the carbonyl group of COOH attacks a proton produced by the auto-ionization of water. The tautomer of the resulting intermediate has a nucleophilic carbon, C1, which is attacked by a lone pair present on the OH group on the other end of the aldonic acid chain. The electrons from the O-H bond of the attacking OH group is w ithdrawn by the O+, and the resulting proton is attacked by a lone pair on the OH group attached to C1. The lone pair from the O of the other OH group attached to C1 forms a second bond between C and O, and a H2O molecule leaves as a leaving group. The electrons from the O-H bond then forms a second bond between C and O, and a proton leaves. A lactone intermediate is formed.Finally, the lactone intermediate is reduced employ a sodium amalgam, Na(Hg), to form the resultant aldohexose monosaccharide (McMurry, 2008). Reagents used are sodium amalgam and sulphuric acid, in rimy solution (Fischer, 1890). Figure 5 below shows the reaction equation. The exact mechanism of reduction by sodium amalgam is outlander at this forefront in time (Keck et al., 1994).Figure 4 Esterification of aldonic acid to form lactone intermediate.Figure 5 Reduction of aldonic acid to resultant sugar.History and developmentThe Kiliani-Fischer synthesis is named after German chemists Heinrich Kiliani and H ermann Emil Fischer. Its original purpose was to elucidate all 16 stereoisomers of aldohexoses, as achieved by Fischer. Key discoveries that to the development of this technique included (1) Louis Pasteurs sagacity that the molecule of tartaric acid came in two forms that were reflect images, or isomers, of one another, and that each of these isomers rotated polarized light in assorted directions (Wagner, 2004, p.240), (2) Jacobus H. vant Hoffs and J. A. Le Bels insight of the concept of an asymmetric carbon atom, that isomers of compounds exist despite undistinguishable chemical formulae because of asymmetric carbon atoms, and the relationship between stereochemistry and optical action at law (Wagner, 2004, p.240), and (3) Fischers creation of phenylhydrazine, a reagent that reacts with sugar molecules to form osazones.Prior to the baring of this technique, relatively little was known about the structural properties of monosaccharides. It was difficult to interpret monosaccha rides because of their tendency to form syrups rather than solids that could be dissolved and crystallized intimately (Wagner, 2004). However, Fischer find phenylhydrazine which when reacted with aldonic acids (formed by oxidation of sugars) forms osazones (Kunz, 2002). These carbohydrate derivatives could be isolated soft through crystallization, and had physical forms that could be distinguished from one another (Kunz, 2002). Their subsequent analysis allowed Fischer to identify and segregate isomers of the monosaccharides (Wagner, 2004). The aldonic acid can be regenerated by addition of baryta water, or aqueous solution of barium hydroxide, to the segregated osazone (Fischer, 1890). The then purified aldonic acid can be evaporated to transform into welling-crystallizing lactone for that study (Fischer, 1890). utilise this technique, Fischer discovered that two distinct monosaccharides, D-glucose and D-mannose, yield the same osazone because osazone formation destroys the dis symmetry about C2 without affecting the rest of the molecule (Wagner, 2004). Furthermore, the lactones of D-glucose and D-mannose turned polarized light in different directions. As such, he concluded that D-glucose and D-mannose have identical structures but were mirror images of one another (Wagner, 2004). However, their exact structures were still unknown.In 1886, Kiliani discovered a method to lengthen the carbon chain of an organic molecule, using cyanide as a reagent to form cyanohydrin (McMurry, 2012). Fischer realized the potential of this husking in advancing the study of carbohydrates, adding on an additional step to switch over the cyanohydrin nitrile group into an aldehyde (McMurry, 2012). Thus, the Kiliani-Fischer synthesis was created. This new technique allowed Fischer to research further into the stereoisomerism of monosaccharides and continue off where he last stopped that D-glucose and D-mannose were stereoisomers but of unknown structures.ApplicationsElucidatio n of aldohexose stereoisomersFigure 5 on the right shows the general structure of a aldohexose. In order to apply the Kiliani-Fischer synthesis in the clearing of aldohexose stereoisomers, Fischer had to first make a starting assumption that the OH group of D-glucose at C5 was on the right incline (Wagner, 2004).L-arabinose is an aldopentose having five carbon atoms. Its exact structure had been deciphered by Fischer, and is asymmetric at C2, C3 and C4 as shown in Figure 6 on the right. Fischer discovered that the Kiliani-Fischer synthesis reborn L-arabinose into both D-glucose and D-mannose (Wagner, 2004). This therefore implied that D-glucose and D-mannose shared the same configuration about C3, C4 and C5 as the analogous carbons in L-arabinose (C2, C3 and C4 respectively) (Wagner, 2004). This insight led Fischer to use L-arabinose in accompaniment with D-glucose and D-mannose as materials for further research.Fischer discovered that oxidizing L-arabinose created a product tha t was optically supple (Wagner, 2004). If the starting assumption made by Fischer was true, then this implied that the OH group at C2 in L-arabinose (and thus C3 in D-glucose and D-mannose) must be on the go away side or the product would be optically inactive (Wagner, 2004).Next, Fischer placed that oxidizing D-glucose and D-mannose resulted in dicarboxylic acids that were optically active (Wagner, 2004). This implied that the OH group at C4 in D-glucose and D-mannose (and thus C3 in L-arabinose) must be on the right side or the product would be optically inactive (Wagner, 2004).Finally, Fischer found that oxidizing D-gulose resulted in the same dicarboxylic acid as that of D-glucose (Wagner, 2004). Through logic, Fischer realized this implied that the OH group at C2 in D-glucose must be on the right side.Piecing unneurotic all the information, Fischer finally determined the exact structure of D-glucose and D-mannose, as shown in Figure 7 below.Problems and valuesThe Kiliani-F ischer synthesis is a commonly used technique in preparing aldoses. However, the last step in the reaction process, reduction, produces mixtures containing product aldoses, unreacted lactone, aldonic acid salts, and alditols (Serianni et al., 1979 p.71). Reduction by sodium amalgam allows the production of acylated aldoses in steep yields but the subsequent removal of the acyl groups often degrades the product aldose (Serianni et al., 1979).An improvement to this method would be to reduce the nitrile over a palladium catalyst (Serianni et al., 1979 McMurry, 2012). This would yield an imine intermediate instead, that can be hydrolysed to an aldehyde.ReferencesFischer, E. (1890). Synthesis in the sugar group. Journal of the American Chemical Society, 12(8), 400-409.Fischer, E. (1902). Syntheses in the purine and sugar group. Nobel Lectures, chemical science 1901, 1921, 21-35.Keck, G. E., Savin, K. A. Weglarz, M. A. (1995). Use of samarium diiodide as an alternative to sodium/mercur y amalgam in the Julia-Lythgoe Olefination. Journal of fundamental Chemistry, 60(10), 31943204.Kiliani-Fischer synthesis (2014). Wikipedia. Retrieved April 2, 2014 from http//en.wikipedia.org/wiki/Kiliani%E2%80%93Fischer_synthesis.Kunz, H. (2002). Emil Fischer unequalled classicist, archetype of organic chemistry, and inspired trailblazer of biological chemistry. Angewandte Chemie International Edition, 41(23), 4439-4451.Magner, J. A. (2004). Emil Fischer (1852-1919) The stereochemical nature of sugars. The Endocrinologist, 14(5), 239-244.McMurry, J. (2008). Organic Chemistry (7th edition). Belmont, CA Thomson stick out/Cole.McMurry, J. (2012). Organic Chemistry (8th edition). Belmont, CA Thomson Brooks/ColeSerianni, A. S., Nunez, H. A. Barker, R. (1979). Carbon-13 enriched carbohydrates Preparation of aldonitrile and their reduction with a palladium catalyst. Carbohydrate Research, 72, 71-78.Solomon, E. P., Berg, L. R., Martin, D. W. (2011). biology (9th edition). Singapore, CA Cengage Learning Asia Pte Ltd.