Hemiacetal and hemiketal forms

Although optical rotation has been one of the most frequently determined characteristics of carbohydrates since its recognition in the late 19th century, the rotational behaviour of freshly prepared solutions of many sugars differs from that of solutions that have been allowed to stand. This phenomenon, known as mutarotation, is demonstrable even with apparently identical sugars and is caused by a type of stereoisomerism involving formation of an asymmetrical centre at the first carbon atom (aldehyde carbon) in aldoses and the second one (keto carbon) in ketoses.

Most pentose and hexose sugars, therefore, do not exist as linear, or open-chain, structures in solution but form cyclic, or ring, structures in hemiacetal or hemiketal forms, respectively. As illustrated for glucose and fructose, the cyclic structures are formed by the addition of the hydroxyl group (―OH) from either the fourth, fifth, or sixth carbon atom to the carbonyl group at position 1 in glucose or 2 in fructose. In the case of five-membered cyclic ketohexose or six-membered cyclic aldohexose, the cyclic forms are in equilibrium with (i.e., the rate of conversion from one form to another is stable) the open-chain structure—a free aldehyde if the solution contains glucose, a free ketone if it contains fructose; each form has a different optical rotation value. Since the forms are in equilibrium with each other, a constant value of optical rotation is measurable; the two cyclic forms represent more than 99.9 percent of the sugar in the case of a glucose solution.

By definition, the carbon atom containing the aldehyde or keto group is called the anomeric carbon atom; similarly, carbohydrate stereoisomers that differ in configuration only at this carbon atom are called anomers. When a cyclic hemiacetal or hemiketal structure forms, the structure with the new hydroxyl group projecting on the same side as that of the oxygen involved in forming the ring is called the alpha anomer; that with the hydroxyl group projecting on the opposite side from that of the oxygen ring is called the beta anomer.

The spatial arrangements of the atoms in these cyclic structures are better shown (glucose is used as an example) in the representation devised by British organic chemist Sir Norman Haworth about 1930; they are still in widespread use. In the formulation the asterisk indicates the position of the anomeric carbon atom; the carbon atoms, except at position 6, usually are not labelled.

The large number of asymmetrical carbon atoms and the consequent number of possible isomers considerably complicates the structural chemistry of carbohydrates.