Kiliani-Fischer synthesis sugars

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

Scheme 8.32 Kiliani-Fischer synthesis of higher sugars.

A sequence known as the Kiliani-Fischer synthesis was developed primarily for extending an aldose chain by one carbon, and was one way in which configurational relationships between different sugars could be established. A major application of this sequence nowadays is to employ it for the synthesis of " C-labelled sugars, which in turn may be used to explore the role of sugars in metabolic reactions. 

The final reaction to be covered in this section is known as the Kiliani-Fischer synthesis. It is a method that converts an aldose to two diastereomeric aldoses that contain one more carbon than the original sugar. The Kiliani-Fischer synthesis is illustrated in the following reaction sequence, which shows the formation of the aldopentoses D-ribose and D-arabinose from the aldotetrose D-erythrose ... 

The addition of HCN to aldehydes has been a well-known reaction since the 19th century, especially in the context of the Kiliani-Fischer synthesis of sugars. Even older is the Strecker synthesis of amino acids by simultaneous reaction of aldehydes with ammonia and HCN followed by hydrolysis. The challenge in recent years has been to achieve face-selectivity in the addition to chiral aldehydes. These face-selective additions, known as nonchelation-controlled processes, refer to the original formulation of Cram s for the reaction of nucleophiles with acyclic chi carbonyl compounds. The chelation-controlled reactions refer also to a formulaticxi of Cram s, but whose stereochemical consequences sometimes differ. 2... 

When the Kiliani-Fischer synthesis is performed on the sugar known as (-)-arabinose, the two sugars known as (-l-)-glucose and (+)-mannose are obtained. This means that (-l-)-glucose and (-l-)-mannose are C-2 epimers in other words, they have the same configuration at C-3, C-4, and C-5. Consequently, (-b)-glucose... 

Because (+)-glucose and (+)-maimose are the products obtained when the Kiliani-Fischer synthesis is carried out on (-)-arabinose, there are only two possibilities for the stracture of (—)-arabinose. That is, if (-l-)-glucose and (+)-mannose are sugars 3 and 4, then (—)-arabinose has the structure shown below on the left on the other hand, if (+)-glucose and (+)-maimose are sugars 5 and 6, then (—)-arabinose has the stracture shown on the right ... 

Kiliani-Fischer synthesis Chain lengthening of. sugars through a cyanohydrin intermediate. 

Ketose A sugar based on ketones—so that a three-carbon chain would be a ketotriose, for example. Kiliani-Fischer synthesis An older method for chain lengthening of sugars through a cyanohydrin... 

The mechanism for this hydrolysis is discussed in Section 17.8H. The preparation of a-hydroxy acids from cyanohydrins is part of the Kiliani-Fischer synthesis of simple sugars (Section 22.9A) ... 

We can be sure that the aldotetroses that we obtain from this Kiliani—Fischer synthesis are both D sugars because the starting compound is D-glyceraldehyde and its chirality center is unaffected by the synthesis. On the basis of the Kiliani—Fischer synthesis, we cannot know just which aldotetrose has both —OH groups on the right and which has the top —OH on the left in the Fischer projection. However, if we oxidize both aldotetroses to aldaric acids, one [d-(—)-erythrose] will yield an optically inactive (meso) product while the other [d-(—)-threose] will yield a product that is optically active (see Practice Problem 22.7). 

The second step of the Kiliani—Fischer synthesis, catalytic reduction with poisoned palladium (p. 452), gives a pair of imines that are hydrolyzed under the reaction conditions to aldoses, each of them one carbon longer than the starting sugar. The new sugars differ from each other only in their stereochemistry at C(2). In other words, they are C(2) epimers. 

The Fischer proof starts with arabinose, arbitrarily assumed to be the D enantiomer. The first critical observation was that the Kiliani-Fischer synthesis applied to D-arabinose led to a pair of D-aldohexoses (as it must).These were D-glucose and D-mannose (Fig. 22.44). Because this synthesis must produce a pair of sugars that... 

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