Classifying sugars and the structure of glucose

A sugar cube, a slice of bread and a sheet of paper

Sugar tastes sweet. Bread tastes of nothing sweet, yet it turns sweet if you chew it for a minute. Paper is not food at all. All three are carbohydrates.

The name comes from an old formula. Many of these compounds fit $\text{C}_\text{x}(\text{H}_{2}\text{O})_\text{y}$, so people called them "hydrates of carbon". Glucose is $\text{C}_{6}\text{H}_{12}\text{O}_{6}$, which is $\text{C}_{6}(\text{H}_{2}\text{O})_{6}$. The rule is only a rough guide. Deoxyribose, $\text{C}_{5}\text{H}_{10}\text{O}_{4}$, is a carbohydrate and does not fit. Acetic acid, $\text{C}_{2}\text{H}_{4}\text{O}_{2}$, fits and is not a carbohydrate.

A better definition is by structure. A carbohydrate is a polyhydroxy aldehyde or a polyhydroxy ketone, or a compound that gives one of these when it reacts with water.

Three groups

We sort carbohydrates by the number of sugar units in the molecule.

• Monosaccharides cannot be broken into smaller sugars by hydrolysis. Glucose, fructose, galactose and ribose are examples.
• Oligosaccharides give 2 to 10 monosaccharide units. A disaccharide, such as sucrose, gives two.
• Polysaccharides give a very large number of units. Starch, cellulose and glycogen are the main ones.

The small, sweet, crystalline carbohydrates that dissolve in water are called sugars. Starch and cellulose are not sugars in this sense: they are not sweet and do not dissolve.

Chemists also use a test. Benedict's and Fehling's solutions are blue solutions of copper(II). A reducing sugar turns them red or orange, because it reduces the copper(II) to red copper(I) oxide. A non-reducing sugar does not. We will see in lesson 3 what decides this.

Aldoses and ketoses

A monosaccharide has either an aldehyde group, $\text{-}\text{CHO}$, or a ketone group, $\text{C}=\text{O}$, with several $\text{-}\text{OH}$ groups on the other carbons.

• An aldose has the carbonyl group at the end of the chain. Glucose is an aldose.
• A ketose has the carbonyl group on carbon 2. Fructose is a ketose.

The number of carbon atoms gives the second part of the name: triose (3), tetrose (4), pentose (5) and hexose (6). So glucose is an aldohexose, fructose is a ketohexose and ribose is an aldopentose.

Drawing a sugar: the Fischer projection

A Fischer projection puts the carbon chain in a vertical line, with the carbonyl carbon at the top. At each stereocentre the horizontal bonds come out towards you, and the vertical bonds go back. The picture below shows four sugars.

Look at the three aldohexoses first. They have the same chain. They differ only in which side the $\text{-}\text{OH}$ groups point. The red groups mark where mannose and galactose differ from glucose.

Two sugars that differ at only one stereocentre are called epimers. Mannose is the C-2 epimer of glucose. Galactose is the C-4 epimer of glucose.

D and L

Glyceraldehyde is the smallest sugar. It has one stereocentre, so it has two forms. The form with the $\text{-}\text{OH}$ on the right in the Fischer projection is D-glyceraldehyde. The one with $\text{-}\text{OH}$ on the left is L-glyceraldehyde.

For a larger sugar, we look at the stereocentre farthest from the carbonyl group, which is C-5 in a hexose. If its $\text{-}\text{OH}$ is on the right, the sugar is a D sugar. If it is on the left, the sugar is an L sugar. Nearly all natural sugars are D sugars.

Do not mix up two different labels. D and L describe the arrangement of atoms. The signs (+) and (-) tell you which way a solution turns plane-polarised light. D-glucose is (+). D-fructose is (-). There is no link between the letter and the sign.

Counting the stereoisomers

Each stereocentre has two possible arrangements. For $n$ different stereocentres the number of stereoisomers is $2^n$.

• An aldohexose has 4 stereocentres (C-2 to C-5), so $2^4 = 16$ stereoisomers. Eight are D sugars and eight are L sugars.
• A ketohexose has 3 stereocentres (C-3 to C-5), so $2^3 = 8$.
• An aldopentose has 3 stereocentres, so there are 8. An aldotetrose has 2, so there are 4.

The L form of a sugar is the mirror image of the D form. Every stereocentre is reversed. A stereoisomer that is not a mirror image, such as mannose against glucose, is a diastereomer.

Set the chain to 6 carbons and the kind to 1. You get 16. Now change the kind to 2. The count drops to 8. A ketose has one stereocentre fewer, because its carbonyl carbon is on C-2.

Practise with new numbers

Try it in Python

The program lists every pattern of four $\text{-}\text{OH}$ groups on the right (R) and on the left (L). It keeps the D sugars and gives each one its name and its mirror image.

How the structure of glucose was found

Glucose was the first sugar to be studied carefully, and the evidence is a good lesson in reasoning. Each fact below tells us one thing about the molecule.

• The formula. Combustion analysis gives 40.0% carbon, 6.7% hydrogen and 53.3% oxygen by mass. This gives the empirical formula $\text{CH}_{2}\text{O}$. The molar mass is about $180\ \text{g/mol}$, so the molecular formula is $\text{C}_{6}\text{H}_{12}\text{O}_{6}$.
• A straight chain of six carbons. Heating glucose for a long time with hydriodic acid gives n-hexane, $\text{CH}_{3}(\text{CH}_{2})_{4}\text{CH}_{3}$. So the six carbons are in one unbranched chain. The balanced equation is $\text{C}_{6}\text{H}_{12}\text{O}_{6} + 14\text{HI} \to \text{C}_{6}\text{H}_{14} + 6\text{H}_{2}\text{O} + 7\text{I}_{2}$.
• Five hydroxyl groups. Acetic anhydride gives a pentaacetate, $\text{C}_{16}\text{H}_{22}\text{O}_{11}$. Five $\text{-}\text{OH}$ groups were acetylated.
• A carbonyl group that is an aldehyde. Glucose adds hydrogen cyanide to give a cyanohydrin and reacts with hydroxylamine to give an oxime. Bromine water oxidises it to gluconic acid, $\text{HOOC}\text{-}(\text{CHOH})_{4}\text{-}\text{CH}_{2}\text{OH}$, which still has six carbons. A ketone could not be oxidised without breaking the chain, so the group is an aldehyde.
• A primary alcohol at the other end. Nitric acid oxidises both ends to give saccharic acid (also called glucaric acid), $\text{HOOC}\text{-}(\text{CHOH})_{4}\text{-}\text{COOH}$. So the last carbon is a $\text{-}\text{CH}_{2}\text{OH}$ group.

Put these together and glucose is 2,3,4,5,6-pentahydroxyhexanal. That is the open-chain structure in the Fischer projection above.

There was a problem. Glucose does not give Schiff's test. It does not add sodium hydrogensulphite. Its pentaacetate does not react with hydroxylamine, which means that an aldehyde is not free there. Something else must be going on, and that is the subject of the next lesson.

Common mistakes

• Counting every carbon as a stereocentre. The aldehyde carbon, the last carbon and the carbonyl carbon of a ketose are not stereocentres.
• Calling any two sugars "epimers". Epimers differ at exactly one stereocentre.
• Reading D as "dextrorotatory". D and L describe structure. The sign of rotation is separate.
• Forgetting that the L form is the full mirror image. Every centre is reversed, not only C-5.

Remember these

• A carbohydrate is a polyhydroxy aldehyde or ketone, or gives one on hydrolysis.
• Aldose: C=O at the end. Ketose: C=O on C-2. Glucose is an aldohexose and fructose a ketohexose.
• $n$ stereocentres give $2^n$ stereoisomers: 16 for an aldohexose and 8 for a ketohexose.
• D or L depends on the last stereocentre. Epimers differ at one stereocentre.
• The evidence for glucose: $\text{C}_{6}\text{H}_{12}\text{O}_{6}$, a straight chain, five $\text{-}\text{OH}$, an aldehyde, and a primary alcohol at the other end.

Check yourself

Try each one on your own first. If you are stuck, open a hint. Then check with Show the answer.

1. How many stereoisomers does an aldopentose have? How many of them are D sugars?

2. D-glucose and D-galactose differ only in the position of the $\text{-}\text{OH}$ on C-4. What are such sugars called?

3. Hydriodic acid reduces glucose to n-hexane. What does this tell us about the carbon skeleton of glucose?

4. Why is glucose called an aldohexose and not a ketohexose?

References

• Nelson and Cox, Lehninger Principles of Biochemistry, 8th edition, Chapter 7 (Carbohydrates and Glycobiology).
• NCERT Chemistry for Class 12, Part II, the chapter Biomolecules (classification of carbohydrates, structure of glucose).
• OpenStax, Organic Chemistry, Chapter 25 (Biomolecules: Carbohydrates).