Monosaccharides: Glucose and Fructose

1.0What are Monosaccharides?

Monosaccharides, also known as simple sugars, are the most basic units of carbohydrates. Their name, from the Greek "mono" (one) and "sacchar" (sugar), signifies that they cannot be hydrolyzed into smaller carbohydrate units. They are polyhydroxy aldehydes or ketones. The general formula for monosaccharides is $(C{H}_{2}O)n$​, where n is typically 3 to 7. Based on the number of carbon atoms, they are classified as trioses (n=3), tetroses (n=4), pentoses (n=5), hexoses (n=6), etc.

The two main categories of monosaccharides are:

• Aldoses: Contain an aldehyde (–CHO) functional group.
• Ketoses: Contain a ketone (>C=O) functional group.

Glucose is an aldohexose, while fructose is a ketohexose.

2.0Glucose: The "Blood Sugar"

Glucose is the most abundant monosaccharide on Earth and serves as a primary source of energy for living organisms. It is also known as dextrose because it is dextrorotatory, meaning it rotates plane-polarized light to the right (+).

Structure of Glucose

Glucose has the molecular formula C₆​H₁₂​O₆​. Its structure can be represented in two forms: a linear open-chain form and a cyclic hemiacetal form.

a) Open-Chain (Fischer) Structure The open-chain structure of glucose, proposed by Emil Fischer, shows it as a six-carbon chain with an aldehyde group at one end (C-1) and five hydroxyl (–OH) groups. One hydroxyl group is on each of the remaining five carbons.

Key features of this structure:

• It has an aldehyde group at C-1.
• It has four chiral carbon atoms (C-2, C-3, C-4, and C-5), which means it can have 2^4=16 possible stereoisomers.
• The hydroxyl group on the last chiral carbon (C-5) determines whether it's a D- or L-sugar. In D-glucose, the –OH on C-5 is on the right side.

b) Cyclic (Haworth) Structure The open-chain structure doesn't fully explain all of glucose's properties, such as its inability to form a bisulfite addition product or its mutarotation. This led to the discovery of its cyclic structure. The cyclic structure is formed by the reaction of the aldehyde group (–CHO) at C-1 with the hydroxyl group (–OH) at C-5. This reaction forms an intramolecular hemiacetal.

This cyclization creates a new chiral center at C-1, known as the anomeric carbon. This results in two new stereoisomers, called anomers:

• α-D-glucose: The –OH group on the anomeric carbon (C-1) is on the same side as the –OH group on C-4 (typically drawn pointing down in the Haworth projection).
• β-D-glucose: The –OH group on the anomeric carbon (C-1) is on the opposite side of the –OH group on C-4 (typically drawn pointing up).

The six-membered cyclic ring is called a pyranose ring (due to its similarity to the pyran ring), hence the names α-D-glucopyranose and β-D-glucopyranose.

Preparation of Glucose

Glucose can be prepared through several methods:

1. From Sucrose (Cane Sugar): Sucrose is hydrolyzed with dilute acid (HCl or H_2​SO_4​) in an alcoholic solution. The reaction yields an equimolar mixture of glucose and fructose: $C_{12}{H}_{22}{O}_{11}+H_{2}O\stackrel{H^{+}}{\to }{C}_6{H}_{12}{O}_6\text{(Glucose)}+C_6{H}_{12}{O}_6\text{(Fructose)}$
2. From Starch: Starch is a polymer of glucose. It is hydrolyzed by boiling with dilute H_2​SO_4​ at 393 K under pressure. $(C_6{H}_{10}{O}_5{)}_n+n{H}_{2}O\stackrel{H^{+},393\text{K}}{\to }n{C}_6{H}_{12}{O}_6\text{(Glucose)}$

Properties of Glucose

• It is a sweet-tasting, crystalline solid that is soluble in water.
• Glucose is a reducing sugar. This is a key property of monosaccharides with a free anomeric carbon that can revert to the open-chain aldehyde form. It reduces Tollens' reagent and Fehling's solution.
• Mutarotation: The specific optical rotation of a freshly prepared solution of glucose changes over time until it reaches a stable equilibrium value. This is due to the interconversion of the α and β forms through the open-chain structure. The equilibrium mixture contains approximately 36% α-D-glucose and 64% β-D-glucose.

Chemical Reactions of Glucose

1. Oxidation:

• With Bromine water ($B{r}_2/H_{2}O$): A mild oxidizing agent. It oxidizes the aldehyde group to a carboxylic acid, forming gluconic acid. This confirms the presence of an aldehyde group.
• With Nitric acid ($HN{O}_3$​): A strong oxidizing agent. It oxidizes both the aldehyde group and the primary alcohol group at C-6 to carboxylic acids, forming saccharic acid.

2. Reduction: With Sodium amalgam (Na/Hg) or Sodium borohydride (NaBH_4​): Reduces the aldehyde group to a primary alcohol, forming sorbitol (glucitol).
3. Reaction with Hydroxylamine ($N{H}_{2}OH$): Forms a glucose oxime, confirming the presence of a carbonyl group.
4. Acetylation with Acetic anhydride: Glucose reacts with acetic anhydride to form pentaacetyl glucose, proving the presence of five hydroxyl groups.
5. Reaction with Hydrogen Cyanide (HCN): Forms a cyanohydrin, which confirms the presence of a carbonyl group.

3.0Fructose: The "Fruit Sugar"

Fructose is a ketohexose found naturally in fruits, honey, and vegetables. It is the sweetest of all naturally occurring sugars.

Structure of Fructose

The molecular formula of fructose is also $C_6{H}_{12}{O}_6$. Its structure is similar to glucose but with a key difference in the carbonyl group.

a) Open-Chain (Fischer) Structure The open-chain structure of fructose shows a ketone group at C-2 and five hydroxyl groups on the remaining carbons.

Key features of this structure:

• It has a ketone group at C-2.
• It has three chiral carbon atoms (C-3, C-4, and C-5).
• Like glucose, the hydroxyl group on the last chiral carbon (C-5) determines its D- or L-configuration. In D-fructose, the –OH on C-5 is on the right side.

b) Cyclic (Haworth) Structure. Fructose also exists in cyclic forms due to the reaction of the ketone group at C-2 with a hydroxyl group. It forms an intramolecular hemiketal. This cyclization results in two cyclic forms:

• Furanose Ring: The ketone group at C-2 reacts with the hydroxyl group at C-5, forming a five-membered ring called a furanose ring (similar to the furan ring). This is the predominant form in its derivatives, like sucrose.
• • α-D-fructofuranose
  • β-D-fructofuranose
• Pyranose Ring: The ketone group at C-2 can also react with the hydroxyl group at C-6, forming a six-membered ring called a pyranose ring. This form exists in the pure crystalline state.

Preparation of Fructose

Fructose is most commonly prepared by the hydrolysis of sucrose, as mentioned earlier. The process yields an equimolar mixture of glucose and fructose.

Properties of Fructose

• It is a sweet, crystalline solid that is highly soluble in water.
• Fructose is also a reducing sugar. Even though it has a ketone group, it can isomerize to glucose and mannose in the presence of an alkali, enabling it to reduce Tollens' and Fehling's reagents. This property is known as enolization.
• L-Fructose: Fructose is levorotatory, meaning it rotates plane-polarised light to the left (-).

Chemical Reactions of Fructose

1. Oxidation: Fructose, a ketone, does not get oxidized easily. However, in the presence of alkaline reagents like Tollens' or Fehling's solution, it rearranges to an aldehyde through enolization and then gets oxidized.
2. Reduction: The ketone group at C-2 is reduced by sodium amalgam or NaBH4​ to form a mixture of sorbitol and mannitol. This is because the reduction of the ketone group creates a new chiral center.
3. Reaction with Hydroxylamine (NH2​OH) and HCN: Similar to glucose, fructose reacts with hydroxylamine to form an oxime and with HCN to form a cyanohydrin, confirming the presence of a carbonyl group.

4.0Monosaccharides (Glucose and Fructose) Examples

Monosaccharides are the simplest carbohydrates and include well-known hexose sugars like glucose and fructose. These examples illustrate key structural and functional distinctions:

• Glucose (Aldohexose): Glucose, also known as dextrose, is a six-carbon sugar featuring an aldehyde group at carbon‑1. It is abundant in nature, found in fruits, honey, and serves as the fundamental energy source for living cells. In aqueous solutions, glucose typically adopts a cyclic pyranose form, forming a six-membered ring via intramolecular hemiacetal formation .
• Fructose (Ketohexose): Fructose is also a six-carbon sugar but contains a ketone group at carbon‑2, classifying it as a ketose. It’s commonly called fruit sugar and is especially sweet. In solution, fructose frequently forms a five-membered furanose ring through hemiketal formation.

5.0Key Differences Between Glucose and Fructose