Aldohexoses Kiliani-Fischer synthesis

Application of the Kiliani-Fischer synthesis to the aldopentose D-arahinose produces aldohexoses D-glucose and D-mannose. Because the Kiliani-Fischer synthesis incorporates the stereocenters of D-arabinose without changes, D-glucose and D-mannose must have the same configurations at carbons 3,4, and 5 as does D-arabinose at carbons 2, 3, and 4, respectively. Furthermore, D-glucose and D-mannose must differ only in their configuration at carbon 2. 

The reasoning behind the Fischer proof is easier to follow if the eight possible D-aldohexoses are arranged in pairs of epimers at C2. These compounds are labeled 1-8 in Figure 27.9. When organized in this way, each pair of epimers would also be formed as the products of a Kiliani-Fischer synthesis beginning with a particular D-aldopentose (lettered A-D in Figure 27.9). 

A D-aldohexose A is formed from an aldopentose B by the Kiliani-Fischer synthesis. Reduction of A with NaBH4 forms an optically inactive alditol. Oxidation of B forms an optically active aldaric acid. What are the structures of A and B ... 

The four D aldopentoses and the eight D aldohexoses derived from them by Kiliani-Fischer synthesis are shown in Figure 25.9 (p. 1052), One of the eight aldohexoses is glucose, but which one ... 

The Ruff degradation and the Kiliani—Fischer synthesis allow us to place all of the aldoses into families or family trees based on their relation to D- or L-glyceraldehyde. Such a tree is constructed in Fig. 22.7 and includes the structures of the D-aldohexoses, 1-8. 

Identify the two aldohexoses that are obtained when D-arabinose undergoes a Kiliani-Fischer synthesis. 

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... 

This, together with the fact that (+)-glucose yields a different but also optically active aldaric acid, establishes 10 as the structure of (-)-arabinose and eliminates 8 as a possible structure for (+)-glucose. Had ( )-arabinose been represented by structure 12, a Kiliani-Fischer synthesis would have given the two aldohexoses, 7 and 8, one of which (7) would yield an optically inactive aldaric acid on nitric acid oxidation. 

When subjected to a Ruff degradation, a D-aldopentose, A, is converted to an aldotetrose, B. When reduced with sodium borohydride, the aldotetrose B forms an optically active alditol. The NMR spectrum of this alditol displays only two signals. The alditol obtained by direct reduction of A with sodium borohydride is not optically active. When A is used as the starting material for a Kiliani-Fischer synthesis, two diastereomeric aldohexoses, C and D, are produced. On treatment with sodium borohydride, C leads to an alditol E, and D leads to F. The NMR spectrum of E consists of three signals that of F consists of six. Propose structures for A-F. 

Two D-aldohexoses (A and A") give optically inactive alditols on reduction. A" is formed from B" by Kiliani-Fischer synthesis. Since B" affords an optically active aldaric acid on oxidation, B" is B and A" is A. The alternate possibility (A ) is formed from an aldopentose B that gives an optically inactive aldaric acid on oxidation. 

Aldotetrose B must be D-threose because the alditol derived from it (o-threitol) is optically active (the alditol from D-erythrose, the other possible D-aldotetrose, would be meso). Due to rotational symmetry, however, the alditol from B (D-threitol) would produce only two NMR signals. Compounds A-F are thus in the family of aldoses stemming from D-threose. Since reduction of aldopentose A produces an optically inactive alditol, A must be D-xylose. The two diastereomeric aldohexoses C and D produced from A by a Kiliani-Fischer synthesis must therefore be D-idose and D-gulose, respectively. E and F are the alditols derived from C and D, respectively. Alditol E would produce only three C NMR signals due to rotational symmetry while F would produce six signals. 

First, let us look at a method for converting an aldose into another aldose containing one more carbon atom, that is, at a method for lengthening the carbon chain. In 1886, Heinrich Kiliani (at the Technische Hochschule in Munich) showed that an aldose can be converted into two aldonic acids of the next higher carbon number by addition of HCN and hydrolysis of the resulting cyanohydrins. In 1890, Fischer reported that reduction of an aldonic acid (in the form of its lactone. Sec. 20.15) can be controlled to yield the corresponding aldose. In Fig. 34.2, the entire Kiliani-Ffscher synthesis is illustrated for the conversion of an aldopentose into two aldohexoses. 

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