D and L Configurations
1.0Introduction
In stereochemistry, D and L configurations are systems for describing the absolute configuration of chiral molecules, especially sugars and amino acids. These notations do not indicate optical activity (i.e., whether a compound is dextrorotatory [+] or levorotatory [−]) but rather refer to the spatial arrangement of atoms around the chiral centre, compared to a reference molecule — glyceraldehyde..
The D/L system was initially proposed based on the optical activity of glyceraldehyde, the simplest carbohydrate with a chiral centre..
- D-(+)-Glyceraldehyde rotates plane-polarized light to the right.
- L-(−)-Glyceraldehyde rotates it to the left.
However, D and L labels were assigned before the absolute configuration (R/S) could be experimentally determined, and they are based on structural analogy rather than optical rotation.
2.0Glyceraldehyde:The Reference Compound
Structure of D-(+)-glyceraldehyde (Fischer projection):
CHO
|
H — C — OH → D-form
|
CH2OH
Structure of L-(−)-glyceraldehyde:
CHO
|
OH — C — H → L-form
|
CH2OH
- The configuration of the asymmetric carbon (the carbon with four different groups) determines whether the molecule is D or L.
- If the OH on the chiral center is on the right in the Fischer projection → D-form.
- If the OH is on the left, it is an L-form.
3.0Fischer Projection
- A Fischer projection is a 2D representation of a 3D organic molecule.
- Vertical lines go behind the plane of the paper.
- Horizontal lines come out of the plane.
- The chiral centre is at the intersection of the horizontal and vertical lines.
4.0D- and L- Carbohydrates
Carbohydrates have multiple chiral centers, but the D or L designation depends only on the configuration of the chiral carbon farthest from the aldehyde (CHO) or keto (C=O) group.
For Aldoses
Aldotetroses (4-Carbon Aldehyde Sugars)
- Two common examples: Threose and Erythrose
- Each has two chiral centers, forming four stereoisomers: D-/L- Threose, D-/L- Erythrose
- Rule:
- If OH on bottom chiral center is on the right → D-form
- If it’s on the left → L-form
Aldopentoses (5-Carbon Aldehyde Sugars)
- Examples: Ribose, Arabinose, Xylose, Lyxose
- Each has three chiral centers → 8 stereoisomers (4 D/L pairs)
- Ribose is the sugar in RNA, most commonly found as D-ribose.
Example: D-glucose
CHO
|
H — C — OH
|
OH — C — H
|
H — C — OH
|
H — C — OH
|
CH2OH
The second-last carbon (C5) has the OH on the right, so it's a D-sugar.
Example: L-glucose
CHO
|
OH — C — H
|
H — C — OH
|
OH — C — H
|
OH — C — H
|
CH2OH
C5 has the OH on the left, so it is a L-sugar.
5.0D- and L- Amino Acids
In amino acids, the D and L configuration is also based on the position of the NH₂ group in the Fischer projection.
General structure of amino acid (Fischer projection):
COOH
|
H — C — NH2
|
R
- If the NH₂ group is on the right → D-amino acid.
- If the NH₂ group is on the left → L-amino acid.
Example: L-alanine
COOH
|
H — C — NH2 → L-alanine
|
CH3
Most naturally occurring amino acids (found in proteins) are in the L-form.
6.0D/L vs (+)/(-)
- D and L refer to configuration (structure).
- (+) and (−) refer to optical rotation (property).
- They are not always correlated.
For example:
So, never assume D = (+) or L = (−) without measurement.
7.0R/S vs D/L Notation
While D/L is relative, R/S configuration is absolute, determined by the Cahn–Ingold–Prelog (CIP) priority rules.
How they differ:
- R/S system looks at the actual 3D configuration.
- D/L compares to glyceraldehyde.
Example:
- L-alanine has the S configuration.
- But not all L-amino acids are S (e.g., L-cysteine is R due to the priority of sulfur)
8.0Racemic Mixtures and Enantiomers
- A racemic mixture contains equal amounts of D and L (or R and S) forms.
- D and L compounds are enantiomers (non-superimposable mirror images).
- They have:
- Same physical properties (except optical rotation)
- Different interactions with other chiral molecules or polarized light
9.0How to Determine D or L Configuration
For sugars
- Draw or obtain the Fischer projection.
- Identify the chiral carbon farthest from the carbonyl group (C=O).
- Look at the position of the OH group on that carbon:
Right → D
Left → L
For amino acids:
- Draw Fischer projection with COOH at top and R group at bottom.
- If NH₂ is:
Right → D
Left → L
Examples
D-mannose vs L-mannose
CHO
|
H — C — OH
|
H — C — OH
|
OH — C — H
|
OH — C — H
|
CH2OH
L-mannose: All chiral centers are mirrored from D-form.
Has two chiral centers.
Still classified as L due to NH₂ group on the left when COOH is at the top.