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

1. Draw or obtain the Fischer projection.
2. Identify the chiral carbon farthest from the carbonyl group (C=O).
3. Look at the position of the OH group on that carbon:
   Right → D
   Left → L

For amino acids:

1. Draw Fischer projection with COOH at top and R group at bottom.
2. If NH₂ is:

Right → D

Left → L

Examples

D-mannose vs L-mannose

• D-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.

•  L-threonine

Has two chiral centers.

Still classified as L due to NH₂ group on the left when COOH is at the top.