Although the R and S system, we are familiar with, can be used to designate the absolute configuration of chiral centers in carbohydrates, an older method, proposed in 1906 by a New York University chemist, M. A. Rosanoff, is often the preferred way of describing the stereochemistry of sugars. This strategy uses the D and L notation and is determined based on the chiral carbon farthest from the C=O carbonyl group (penultimate carbon):

 

 

After locating the farthest carbon from the C=O group, you determine the configuration simply based on the position of the OH group:

• In D-sugars the OH group on the chiral center farthest from the carbonyl is on the right.
• In L-sugars the OH group on the chiral center farthest from the carbonyl is on the left.

The D and L notation is applied in reference to glyceraldehyde which naturally occurs in the D form. Its enantiomer, the L-glyceraldehyde is synthesized in the laboratory.

 

 

Interestingly, in many experiments carried out by Emil Fischer and other scientists, it was determined that shortening the carbon chain of most naturally occurring carbohydrates, it is possible to obtain the D-glyceraldehyde. This indicated that most natural carbohydrates have a D configuration.

For example, glucose one of the most common and important carbohydrates also used extensively for the initial studies, was found to exist naturally as a D isomer. The enantiomer, L-glucose can still be prepared synthetically:

 

 

Notice that the absolute configuration of all the chiral centers are inverted and therefore, these isomers are enantiomers. And this is important information especially if you’re taking a test like MCAT as questions related to the relationship of carbohydrates occur quite often.

Remember – D and L isomers are enantiomers! All the chiral centers are inverted when switching from D to L configuration and vice versa.

 

 

D and L Notation of Amino Acids

There are hundreds of amino acids, however, we will discuss the stereochemistry of only 20 of them. And it is because these 20 amino acids can be found in peptides and proteins of humans and other mammals.

Amino acids are also characterized by the D and L notation and just like there is a trend of carbohydrates naturally occurring in D form, amino acids also have preferred stereochemistry. Except for glycine, which is achiral, all of them are L amino acids.

 

 

Interestingly, 18 out of these 19 amino acids have an S configuration and only Cysteine, being an L amino acid, happens to have an R configuration:

 

The reason for this exception is the fact that in Cysteine, there is a sulfur connected to the carbon on the stereogenic center, and because of its higher atomic number, it takes the priority over the COOH group which does not happen in other amino acids. 

 

Are D and L Always Enantiomers?

I do want to bring up an additional note about the relationship of D and L isomers. Yes, we stated that D and L isomers are enantiomers since all the chiral centers have opposite configuration. This is true, however, when dealing with cyclic forms of sugars, you need to keep in mind epimers which are diastereomers that differ in the configuration of only one chiral center. And if these diastereomers are cyclic hemiacetals like sugars are, then they are classified as anomers. One example is the relationship between ɑ-D-glucose and β-D-glucose:

 

 

This, however, fits here more as a side note and we will discuss the details about epimers and anomers in a separate post.

 

 

D and L vs (+) and (-)

Even though the “D” notation was initially used as an abbreviation to dextrorotatory (turning the plane of polarized light clockwise) since D-glucose is in fact dextrorotatory, it was found later that not all D sugars are dextrorotatory. For, example, D-Erythrose rotates the plane of polarized light counterclockwise and therefore, it is levorotatory.

 

 

Therefore, D and L are not related to the optical rotation and the direction of rotation is given by the (+) and (-) signs or by the lowercase (d) and (l).

So, remember:

• Just like the (R) and (S) designations, the D and L notation is not necessarily related to the optical rotation. There can be a sugar which is D-(+) and one that is D-(-). Same for the L isomers.
• Don’t confuse this with the lowercase d and l notation as these do stand for dextrorotatory (+) and levorotatory (-).

 

Why do we use D and L instead of R and S?

The main advantage of using the D and L notation is its brevity. For example, using D-glucose is much easier than (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal and changing each of the R  and S designation for the enantiomer is not an efficient approach either – L-glucose sounds better than (2S,3R,4S,5S)-2,3,4,5,6-pentahydroxyhexanal.

An alternative way of compressing the configuration of all the chiral centers in one symbol is the (+) and (-) signs of the optical rotation. The problem, however, is that the optical rotation can vary depending on the temperature, solvent, and the light source.

 

Now, speaking of carbohydrates with multiple chiral centers: we will go over the main examples, classify and name them in the following post “Aldoses and Ketoses” as there is too much new information there.

 

Need some practice on carbohydrates?

Check this Multiple-Choice, summary quiz on the structure and reactions of carbohydrates with a 40-min video solution!

 

Check also in Carbohydrates

• Carbohydrates – Structure and Classification
• Erythro and Threo
• D and L Sugars
• Aldoses and Ketoses: Classification and Stereochemistry
• Epimers and Anomers
• Converting Fischer, Haworth, and Chair forms of Carbohydrates
• Mutarotation
• Glycosides
• Isomerization of Carbohydrates
• Ether and Ester Derivatives of Carbohydrates
• Oxidation of Monosaccharides
• Reduction of Monosaccharides
• Kiliani–Fischer Synthesis
• Wohl Degradation