Monosaccharides: Classification and Structure

Carbohydrates: Polyhydroxy aldehydes or polyhydroxy ketones, or substances that yield these upon hydrolysis.

Classification

• Monosaccharides: Simplest sugars, cannot be hydrolyzed (e.g., Glucose, Fructose).
  • By functional group: Aldose (aldehyde, e.g., glucose) or Ketose (ketone, e.g., fructose).
  • By number of carbons: Triose (3C), Tetrose (4C), Pentose (5C, e.g., Ribose), Hexose (6C, e.g., Glucose).
  • Combined: e.g., Glucose is an Aldohexose. Fructose is a Ketohexose.
• Disaccharides: Two monosaccharides joined by a glycosidic linkage (e.g., Sucrose, Lactose).
• Polysaccharides: Polymers of many monosaccharide units (e.g., Starch, Cellulose).

Constitution and Configuration of Glucose

Glucose (C₆H₁₂O₆) is an aldohexose. Its structure was determined by a series of reactions:

1. Elemental Analysis & Molar Mass: Showed formula is C₆H₁₂O₆.
2. Reduction with HI: Gives n-hexane, proving the 6 carbons are in a straight, unbranched chain.
3. Reaction with NH₂OH and HCN: Forms an oxime and cyanohydrin, proving the presence of a carbonyl group (C=O).
4. Oxidation with Br₂ water (mild): Gives gluconic acid (a 6C carboxylic acid), proving the carbonyl is an aldehyde (CHO).
5. Acetylation with Acetic Anhydride: Forms a pentaacetate, proving the presence of five -OH groups.
6. Oxidation with conc. HNO₃ (strong): Oxidizes both the -CHO and the primary alcohol (-CH₂OH) to -COOH, giving a dicarboxylic acid (Saccharic acid). This proves one -OH group is a primary alcohol.

Absolute Configuration: The spatial arrangement of the four chiral centers (C2, C3, C4, C5) was determined by Emil Fischer. Glucose belongs to the D-series because the -OH on C5 (the highest-numbered chiral center) is on the right in the Fischer projection.

Fructose

Fructose (C₆H₁₂O₆) is a ketohexose. It is a functional isomer of glucose. Its carbonyl group is at C2. It also belongs to the D-series.

Epimers, Anomers, and Mutarotation

Epimers

Epimers: Diastereomers that differ in configuration at only one chiral center.

• D-Glucose and D-Mannose are C2 epimers.
• D-Glucose and D-Galactose are C4 epimers.

Anomers

Monosaccharides exist mainly in cyclic hemiacetal (for aldoses) or hemiketal (for ketoses) forms. This cyclization occurs when an -OH group (usually C5) attacks the carbonyl carbon (C1).

This cyclization creates a new chiral center at the original carbonyl carbon (C1 for glucose, C2 for fructose). This new center is called the anomeric carbon.

Anomers: Epimers that differ in configuration *only* at the anomeric carbon.

• α-anomer: The -OH group on the anomeric carbon is trans to the -CH₂OH group (C6). (In a Haworth projection, it points down).
• β-anomer: The -OH group on the anomeric carbon is cis to the -CH₂OH group (C6). (In a Haworth projection, it points up).

Mutarotation

Mutarotation: The spontaneous change in optical rotation observed when a pure anomer of a sugar is dissolved in water.

Example:
Pure α-D-glucose has a specific rotation [α] = +112°.
Pure β-D-glucose has a specific rotation [α] = +18.7°.
When either is dissolved in water, the rotation slowly changes until it reaches a stable equilibrium value of +52.7°.

Reason: In solution, the ring opens (to the open-chain aldehyde form) and re-closes, forming an equilibrium mixture of the α-anomer (36%), the β-anomer (64%), and a trace amount of the open-chain form. The β-anomer is more stable because its -OH group is equatorial.

Ring Structure and Projections

Ring Size Determination

Glucose and Fructose form stable 5- or 6-membered rings.

• Pyranose: A 6-membered ring containing oxygen (formed by C5-OH attacking C1). This is the predominant form for D-Glucose (Glucopyranose).
• Furanose: A 5-membered ring containing oxygen (formed by C4-OH attacking C1).

Fructose exists as a Fructopyranose (6-membered ring) in its free state, but as a Fructofuranose (5-membered ring) when it is part of sucrose.

Haworth Projections

A way to represent the 3D cyclic structure of sugars on a 2D plane. The ring is drawn as a flat polygon (hexagon for pyranose, pentagon for furanose) viewed from the side.

Rules for drawing from a Fischer Projection (for D-sugars):

1. Draw the basic ring with Oxygen at the back-right corner.
2. Any group on the RIGHT in the Fischer projection points DOWN in the Haworth.
3. Any group on the LEFT in the Fischer projection points UP in the Haworth.
4. For D-sugars, the -CH₂OH group (C6) always points UP.
5. For the anomeric -OH (C1): α is down, β is up. (Mnemonic: "Alpha-Below, Beta-Above").

Interconversions and Chain Lengthing/Shortening

Interconversion of Aldose and Ketose

In a basic solution (e.g., dilute alkali), glucose, fructose, and mannose are interconvertible. This happens via an enediol intermediate (Lobry de Bruyn-van Ekenstein transformation). This is why fructose is a reducing sugar even though it's a ketone; it isomerizes to glucose and mannose (aldoses) in the basic test solution (Fehling's or Tollen's).

Chain Lengthing: Kiliani-Fischer Synthesis

This method converts an aldose into a new aldose with one additional carbon atom.

Steps (e.g., Aldopentose → Aldohexose):

1. Cyanohydrin Formation: Aldose + HCN. This reaction is not stereospecific and creates *two* epimeric cyanohydrins (because a new chiral center is formed at C2).
2. Hydrolysis: The nitrile (-CN) is hydrolyzed to a carboxylic acid (-COOH).
3. Lactone Formation & Reduction: The acid forms a lactone (cyclic ester), which is then reduced with a specific reagent (e.g., Na-Hg) to an aldehyde.

Result: An aldopentose (like D-Arabinose) gives two C2-epimeric aldohexoses (D-Glucose and D-Mannose).

Chain Shortening: Ruff and Wohl Degradation

These methods convert an aldose into a new aldose with one less carbon atom.

• Ruff Degradation:
  1. Aldose is oxidized with Br₂ water → Aldonic acid.
  2. Oxidative decarboxylation using Fenton's reagent (H₂O₂ + Fe³⁺ salt) → Aldose with one less carbon.
• Wohl Degradation: (A more common method)
  1. Aldose + NH₂OH → Oxime.
  2. Dehydration with Acetic Anhydride → Cyanohydrin (acetylated).
  3. Elimination with a base (e.g., Ag⁺) → Aldose with one less carbon.

Disaccharides

Two monosaccharides joined by a glycosidic linkage, which is an acetal bond formed between the anomeric carbon of one sugar and an -OH group of another.

Sucrose (Table Sugar)

• Structure: Composed of α-D-Glucose and β-D-Fructose.
• Linkage: The bond is between the anomeric carbons of *both* units: α-1,β-2 glycosidic linkage.
• Properties:
  • Since *both* anomeric carbons are locked in the bond, neither ring can open up.
  • Therefore, sucrose cannot undergo mutarotation and is a NON-REDUCING sugar.

Lactose (Milk Sugar)

• Structure: Composed of β-D-Galactose and D-Glucose.
• Linkage: A β-1,4 glycosidic linkage (from C1 of galactose to C4 of glucose).
• Properties:
  • The anomeric carbon (C1) of the *glucose* unit is free (it's a hemiacetal).
  • Therefore, the glucose ring can open and close.
  • Lactose exhibits mutarotation and is a REDUCING sugar.

Polysaccharides

Polymers made of hundreds or thousands of monosaccharide units. Also called glycans.

Starch

The primary energy storage polysaccharide in plants. It is a polymer of α-D-Glucose. It consists of two components:

1. Amylose (20-30%): A linear, unbranched chain of α-D-glucose units joined by α-1,4 glycosidic linkages. This structure forms a helix.
2. Amylopectin (70-80%): A highly branched structure. It has linear chains (α-1,4 linkages) with branches every 24-30 residues. The branch points are α-1,6 glycosidic linkages.

Cellulose

The primary structural component of plant cell walls. It is a polymer of β-D-Glucose.

• Structure: A long, linear, unbranched chain of β-D-glucose units joined by β-1,4 glycosidic linkages.
• Properties: The β-linkage allows the chains to be very straight. These straight chains align parallel to each other, forming extensive hydrogen bonds. This makes cellulose fibers incredibly strong and insoluble in water.
• Note: Humans cannot digest cellulose because we lack the *cellulase* enzyme needed to break β-1,4 linkages. We can only digest starch (α-1,4 linkages).