Chapter 24: Carbohydrates study notes

Chapter 24: Carbohydrates

Overview

This chapter focuses on carbohydrates, their classifications, structures, reactions, and their importance in biological systems.

Preparation for This Chapter

To fully understand the material in this chapter, it may be necessary to review the following topics:

Chair Conformations (section 4.11)
Haworth Projections (section 4.14)
Fischer Projections (section 5.7)
Hemiacetals and Acetals (section 19.5)
Reduction of Aldehydes and Ketones (section 19.9)

24.1 Introduction to Carbohydrates

Carbohydrates, commonly referred to as sugars, are defined as polyhydroxy aldehydes or ketones.
They are naturally synthesized in nature through the process of photosynthesis, which converts carbon dioxide (CO₂) and water (H₂O) into carbohydrate structures.

24.2 Classification of Monosaccharides

Monosaccharides are simple sugars that can contain multiple chiral centers. The Fischer projection is often utilized to represent their configuration.
They are classified as follows:
  - Aldose: Contains an aldehyde group and is prefixed with "aldo-".
  - Ketose: Contains a ketone group and is prefixed with "-keto".
  - The notation using di, tri, tetr, pent, hex, hept indicates the number of carbon atoms present.

Simple Sugars and Chirality

Glyceraldehyde is identified as the simplest aldose and contains one chiral center.
In the classification of D and L sugars, D-sugars are characterized by the hydroxyl (OH) group at the chiral center farthest from the carbonyl group being located on the right-hand side in the Fischer projection.
  - Examples:
    - D-Glyceraldehyde
    - L-Glyceraldehyde

D and L Designations

It is crucial to distinguish that the terms dextrorotatory and levorotatory do not correspond to the "D" and "L" designations:
- A D-sugar has an “R” configuration at the furthest chiral center, whereas an L-sugar has “S” configuration.
There exist four possible aldotetroses, two of which are D-sugars, and the other two are their enantiomers termed L-Erythrose and L-Threose.

Chirality In Aldopentoses and Aldohexoses

Aldopentoses consist of three chirality centers, leading to the possibility of $2^3 = 8$ stereoisomers, with the D forms being naturally occurring.
Aldohexoses have four chiral centers, resulting in $2^4 = 16$ possible stereoisomers, with eight naturally occurring D sugars identified.

24.3 Configuration of Aldoses

The D and L configurations of aldoses manifest in various naturally occurring sugars such as D-Ribose, D-Glucose, and D-Galactose, among others.

24.4 Ketoses

Naturally occurring D-ketoses represent another important class of monosaccharides.

24.5 Cyclic Structure of Monosaccharides

Monosaccharides undergo ring-closing through hemiacetal formation, favoring 5-membered and 6-membered rings (hemiacetals).
The anomeric carbon (C1) creates a new chiral center upon cyclization, leading to the formation of either a pyranose (6-membered) or a furanose (5-membered) ring.
The terms anomers are assigned upon cyclization where:
- α-anomer: The anomeric –OH group is trans to the –CH₂OH group.
- β-anomer: The anomeric –OH group is cis to the –CH₂OH group.
Mutarotation describes the dynamic equilibrium between α and β anomers and tends to be accelerated under acid or base conditions.

Pyranose Ring Conformation

Pyranose rings can be drawn as Haworth projections or chair conformations. The chair conformation offers a more accurate representation of the three-dimensional structure.
D-Glucose is distinguished as the only sugar where all substituent groups are in equatorial positions, rendering it the most stable and abundant sugar in nature.
The furanose form of D-fructose is frequently involved in biochemical reactions, with the sugar able to interconvert between both furanose and pyranose forms.

24.6 Reactions of Monosaccharides

Hydroxy groups of monosaccharides can be converted into esters to enhance solubility in organic solvents, with excess reagent leading to complete reaction of all free hydroxy groups.
Furthermore, hydroxy groups may be transformed into ethers via Williamson ether synthesis, utilizing silver oxide (Ag₂O) as the base.
A cyclic hemiacetal can react with an alcohol under acidic conditions to form an acetal, resulting in a mixture of α and β glycosides.
The mechanism of glycoside formation parallels that of typical acetal formation.
Under strongly basic conditions, aldoses can undergo epimerization at C2 through an enediol intermediate. Epimers are diastereomers that differ in configuration at only one chiral center.
Monosaccharides may also be reduced to alditols using sodium borohydride (NaBH₄), with D-glucitol, also known as D-sorbitol, serving as a sugar substitute.
Aldose oxidation leads to the formation of aldonic acids, requiring a mild oxidizing agent to avoid oxidation of alcohol groups. Additionally, specific oxidation tests can be employed to distinguish between aldoses and ketoses, particularly Tollen’s test and Fehling’s test.
Glycosides, being acetals, are not classified as reducing sugars and will not oxidize. A stronger oxidizing agent can convert an aldose and a primary alcohol into an aldaric acid.

Kiliani-Fischer Synthesis and Wohl Degradation

The Kiliani-Fischer synthesis extends the carbon chain length of a sugar by one carbon atom. This process involves converting the cyano group into an aldehyde.
Conversely, the Wohl degradation reduces the carbon chain length by one, which can be advantageous for characterizing aldoses.

24.7 Disaccharides

Disaccharides consist of two sugars linked together via a glycosidic linkage. Typically, the glycosidic oxygen connects C1 to C4, thereby forming a 1,4-disaccharide. For instance, maltose is classified as a reducing sugar.
Cellobiose and maltose differ solely in the stereochemistry at their anomeric carbons. Other disaccharides include lactose and sucrose, with the latter being a non-reducing sugar that can be broken down by various organisms into fructose and glucose.

24.8 Polysaccharides

Cellulose is a polysaccharide comprising 7000 to 12000 glucose units linked by β-glycosidic bonds. Its strong hydrogen bonding among strands grants rigidity to wood and plant material.
Starch, primarily composed of glucose units, consists of two components: amylose (20%) and amylopectin (80%). Amylopectin features glycosidic branches off of C6.
Amino sugars, such as glucosamine, are significant in biological systems, forming polysaccharides like chitin, which has enhanced hydrogen bonding due to N-acyl groups and is crucial for exoskeletons in insects and arthropods.

24.9 N-Glycosides

N-glycosides arise when carbohydrates react with an amine in acidic conditions. For example, nitrogenous bases in DNA connect to deoxyribose units through N-glycosidic linkages, resulting in nucleoside formation.
In RNA, ribose generates ribonucleosides, whereas deoxyribose forms deoxyribonucleosides. Four distinct heterocyclic amines attach to deoxyribose, forming DNA nucleosides.
Nucleosides link to phosphate groups forming nucleotides, which connect through phosphoester bonds to create the complete DNA strand or polynucleotide. Notably, nucleotides can interact through hydrogen bonding between base pairs.

Structural Differences Between RNA and DNA

Notably, RNA differs structurally from DNA:
- The sugar present in RNA is ribose.
- RNA includes uracil instead of thymine, playing a pivotal role in translating the genetic information encoded in DNA into functional molecules such as proteins and enzymes.

24 - Review of Reactions

The final section reviews the various reactions and transformations of carbohydrates, summarizing key points covered throughout the chapter, emphasizing their function in biological systems.

This exhaustive overview of carbohydrates integrates biochemical principles and constructs a fundamental understanding of their importance in organic chemistry and biology.

Note: All content is provided with citations to Klein's Organic Chemistry 3e, and it is advised to cross-reference with original material for in-depth study and clarity.