Carbohydrates cyclic hemiacetal formation

Aldoses incorporate two functional groups C=0 and OH which are capable of react mg with each other We saw m Section 17 8 that nucleophilic addition of an alcohol function to a carbonyl group gives a hemiacetal When the hydroxyl and carbonyl groups are part of the same molecule a cyclic hemiacetal results as illustrated m Figure 25 3 Cyclic hemiacetal formation is most common when the ring that results is five or SIX membered Five membered cyclic hemiacetals of carbohydrates are called furanose forms SIX membered ones are called pyranose forms The nng carbon that is derived... 

Aldoses exist almost exclusively as their cyclic hemiacetals very little of the open chain form is present at equilibrium To understand their structures and chemical reac tions we need to be able to translate Fischer projections of carbohydrates into their cyclic hemiacetal forms Consider first cyclic hemiacetal formation m d erythrose To visualize furanose nng formation more clearly redraw the Fischer projection m a form more suited to cyclization being careful to maintain the stereochemistry at each chirality center... 

Furanose form (Section 25 6) Five membered nng ansing via cyclic hemiacetal formation between the carbonyl group and a hydroxyl group of a carbohydrate... 

If the carbonyl and the hydroxyl group are in the same molecule, an intramolecular nucleophilic addition can take place, leading to the formation of a cyclic hemiacetal. Five- and six-membered cyclic hemiacetals are relatively strain-free and particularly stable, and many carbohydrates therefore exist in an equilibrium between open-chain and cyclic forms. Glucose, for instance, exists in aqueous solution primarily in the six-membered, pyranose form resulting from intramolecular nucleophilic addition of the -OH group at C5 to the Cl carbonyl group (Figure 25.4). The name pyranose is derived from pyran, the name of the unsaturated six-membered cyclic ether. 

In this example the oxygen of the hydroxy group acts as an intramolecular nucleophile. Recall from Section 8.13 that intramolecular reactions are favored by entropy. Therefore, the formation of a cyclic hemiacetal has a larger equilibrium constant than a comparable intermolecular reaction. This reaction is especially important in the area of carbohydrates (sugars) because sugars contain both carbonyl and hydroxy functional... 

Since a hemiacetal is formed so easily from a carbonyl compound and alcohol, it is not surprising to find that carbohydrates (polyhydroxy derivatives of aldehydes and ketones) frequently exist as cyclic structures in which a hemiacetal linkage is formed intramolccularly. Furthermore, since hemiacetal formation is a reversible process, many carbohydrates exhibit the phenomenon of mutarotation. The liberation of the free aldehyde (V) from the internal hemiacetal of the sugar (IV) destroys the optical activity of the hemiacetal carbon atom (in this case carbon 1), and reformation results in the formation of an equilibrium mixture of two diastereoisomers. 

Hemiacetal formation is fundamental to the chemistry of carbohydrates (see Section 11.1). Glucose, for example, contains an aldehyde and several alcohol groups. The reaction of the aldehyde with one of the alcohols leads to the formation of a cyclic hemiacetal (even without acid catalysis) in an intramolecular reaction. 

Finally, in this vein, it is important to note that the carbohydrates (Chapter 11) composing significant amounts of our biosphere commonly exist as hemiacetals and hemiketals, and thus the cyclic forms of glucose (a pair of diasteromeric pyrans) (Table 8.6, item 13) predominate over the open form, which lies in equilibrium between them (Scheme 8.53). Indeed, shorn of its elaborate extra functionality, the cyclization simply represents the same sort of hemiacetal formation seen with methanol (CH3OH) and benzenecarbaldehyde (benzaldehyde, CeHsCHO) (Table 8.6, item 11) shown above (Scheme 8.51). 

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