Question

When discussing sugars, what are intramolecular hemiacetals and hemiketals and why are they important? Give two examples

Answer 1

The term ketal is used to identify structures associated with ketones rather than aldehydes and the term acetal was used for thealdehyde. Formation of an acetal occurs when the hydroxyl group of a hemiacetal becomes protonated and is lost as water.

Hemiacetals and hemiaketals are formed under acidic conditions when an aldehyde or ketone reacts with an alcohol, respectively. The acidic condition protonates the carbonyl carbon on the aldehyde or ketone, followed by a nucleophilic attack of the hydroxyl group on the alcohol on the carbonyl carbon (electrophile). In monosaccharides, their physical structure can exist either as an open chain or a cyclized ring. The ring structure is more energetically stable and is more common in the case of glucose, fructose and ribose. There are two possible ring formations for these sugars, known as pyranose and furanose formations. Pyranose rings are formed from aldoses (aldehyde sugars) and furanose rings are formed from ketoses . Pyranoses are 6 membered rings that resemble the structure of a pyran, whereas furanoses are 5 membered rings that resemble a furan. In hexoses, for example, the C-5 hydroxyl group acts as the alcohol that attacks the C-1 aldehyde carbonyl carbon . This results in an intramolecular hemiacetal at the C-1 position. To form a intramolecular hemiaketal, the C-5 hydroxyl group of a ketohexose attacks the C-2 keto group to form the 5 membered ring, furanose.

It is possible for pentoses and hexoses to cyclize. In fact, many 5- or 6-carbon sugars, such as glucose, ribose, and fructose, exist predominantly as cyclic molecules. The carbonyl group in ketoses and aldoses reacts with an alcohol group within the same sugar molecule. This intramolecular reaction produces either an intramolecular hemiacetal or hemiketal. If the resulting cyclic sugar is a 5-membered ring, it is a furanose. If the resulting cyclic sugar is a 6-membered ring, it is a pyranose. Only the 5-membered and the 6-membered ring can be formed because they are the only types of ring formations that are energetically favored. It is important to note that when sugar undergoes a cyclic transformation, an anomeric carbon is formed in the process. An anomeric carbon is the hemiacetal or hemiketal carbon where there can be two different configuration in cyclic sugar.

eg: as described above glucopyranose formation