Carbohydrates cyanohydrin formation

The chemistry of carbohydrates has sometimes been referred to as a marriage between the chemistry of alcohols and that of aldehydes and ketones. In the preceding sections, we examined oxidations and reductions of carbohydrates, cyanohydrin formation, Fischer glycosidation, and processes that involve enolization. All of these reactions involve carbonyl groups in carbohydrates. In this section, we will consider the reactions of the hydroxyl groups of carbohydrates, starting with their conversion to esters. 

The use of sodium amalgam originates with E. Fischer. The method was a cornerstone of his aldose homologation (cyanohydrin formation, hydrolysis, lactone formation and reduction) which was so important to the development of carbohydrate chemistry. Although the yields obtained by Fischer were moderate ca. 20-50%), more recent work by Sperber et al. has resulted in significant improvements. In particular, they discovered that control of the pH of the reaction mixture was very important. At pH 3-3.5, yields in the range 52-82% were obtained with a variety of aldonolactones. As an example, the preparation of arabinose is shown in equation (4). If the pH was allowed to rise, yields were lower due to overreduction. Methyl esters of aldonic acids could also be used as substrates. 

Cyclic Forms of Carbohydrates 23.21 Cyanohydrin Formation and Chain... 

Kiliani-Fischer synthesis is a means of lengthening the carbon backbone of a carbohydrate. The process begins with the reaction of hydrogen cyanide (HCN) with an aldehyde to produce a cyanohydrin. Treatment of the cyanohydrin with barium hydroxide followed by acidification yields an aldose with an additional carbon atom, as shown in Figure 16-16. The formation of the cyanohydrin creates a new chiral center as a racemic mixture. 

Kiliani method Used in carbohydrate chemistry to extend the length of the carbon chain by one carbon atom. Following the formation of a cyanohydrin of the corresponding ketone, the nitrile group is then hydrolysed to give the a-hydroxycarboxylic acid. 

Overall, the net result is the ability to shorten a carbohydrate chain by one carbon atom. Conversion of the aldehyde into a cyano group is accomplished via oxime formation (as seen in Section 20.6) followed by dehydration. The resulting cyanohydrin then loses HCN when treated with a strong base to afiFord the new carbohydrate that has one less carbon atom than the starting carbohydrate ... 

Emil Fischer s result involving cyanide additions to carbohydrates had demonstrated the power of diastereoselective synthesis early as the 1890s (Equation 1) [4, 34,162]. The corresponding enantioselective formation of cyanohydrins has been the subject of immense efforts. It has long been appreciated that optically active cyanohydrins are synthetically useful intermediates that can be elaborated into a number of chiral building blocks, such as hydroxy acids. In general, there are three main classes of catalysts for the preparation of chiral cyanohydrins enzymes, cyclic dipeptides, and transition metal complexes [163-166]. 

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