Carbohydrates 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... 

Many natural compounds include heterocyclic systems constructed by hemiacetal formation between a hydroxyl group and a keto group of the chain in a 1,4- or 1,5-relative disposition. It is advantageous in a retrosynthetic analysis to take this point into account and to devise a disconnection next to the carbonyl group. Moreover, the synthetic connection does not involve chiral center formation. An obvious translation of this principle in carbohydrate chemistry is the formation of a carbon-carbon bond at the anomeric center by nucleophilic addition to lactones. However, other methods have also been devised to reach this goal. 

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. 

M. F. Ishak and T. J. Painter, Kinetic evidence for hemiacetal formation during the oxidation of dextran in aqueous periodate, Carbohydr. Res., 64 (1978) 189-197. 

Tf20 in combination with sulfoxides lacking a-protons, such as diphenylsulfoxide or dibenzothiophene sulfoxide, generates a sulfoxonium triflate, which is capable of effecting the formation of glycosides from carbohydrate hemiacetals and oxygen nucleophiles. This is a dehydrative glycosylation, and appears to proceed by way of a sulfoxonium intermediate (eq 72). ... 

We have already described an important reaction of carbohydrates— the formation of glycosides under acid-catalyzed conditions (Section 23.14). Glycoside formation drew our attention to the fact that an OH group at the anomeric carbon of a furanose or pyranose form differs in reactivity from the other OH groups of a carbohydrate. It also demonstrated that what looks like a new reaction is one we saw before in a different guise. Mechanistically, glycoside formation is just a structural variation on the aldehyde hemiacetal acetal theme we saw when discussing the reactions of aldehydes and ketones. 

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). 

Figure 39 illustrates that the aldehyde group at C-1 and the hydroxyl group at C-5 come rather close together. This proximity facilitates the reaction leading to hemiacetal formation. Aldehydes in general can add hydroxyl compounds to the C=0 bond (cf. Chapt. 1-2). If H—0—H is added, the product is the hydrate of the aldehyde if an alcohol is added the hemiacetal is formed. Full acetals (or simply acetals ) arise from hemiacetals plus alcohols by elimination of water. This reaction is the basis for glycoside formation by carbohydrates (see formulas below). 

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