6.4: Diastereómeros - más de un centro quiral

Objetivo de aprendizaje

• reconocer y clasificar diastereómeros

Los diastereómeros son estereoisómeros con dos o más centros quirales que no son enantiómeros. Los diastereómeros tienen diferentes propiedades físicas (puntos de fusión, puntos de ebullición y densidades). Dependiendo del mecanismo de reacción, los diastereómeros pueden producir diferentes productos estereoquímicos.

Introducción

Hasta el momento, hemos estado analizando compuestos con un solo centro quiral. A continuación, dirigimos nuestra atención a aquellos que tienen múltiples centros quirales. Comenzaremos con algunos azúcares estereoisoméricos de cuatro carbonos con dos centros quirales.

Para evitar confusiones, simplemente nos referiremos a los diferentes estereoisómeros por letras mayúsculas.

Mire primero el compuesto A a continuación. Ambos centros quirales en tienen la configuración R (¡debes confirmarlo tú mismo!). La imagen especular del Compuesto A es el compuesto B, que tiene la configuración S en ambos centros quirales. Si tuviéramos que recoger el compuesto A, darle la vuelta y ponerlo junto al compuesto B, veríamos que no son superponibles (de nuevo, ¡confirme esto usted mismo con sus modelos!). A y B son imágenes especulares no superponibles: en otras palabras, enantiómeros.

Ahora, mire el compuesto C, en el que la configuración es S en el centro quiral 1 y R en el centro quiral 2. Los compuestos A y C son estereoisómeros: tienen la misma fórmula molecular y la misma conectividad de enlace, pero una disposición diferente de átomos en el espacio (recordemos que esta es la definición del término 'estereoisómero). Sin embargo, no son imágenes especulares entre sí (¡confirma esto con tus modelos!) , y así no son enantiómeros. Por definición, son diastereómeros el uno del otro.

Observe que los compuestos C y B también tienen una relación diastereomérica, por la misma definición.

Entonces, los compuestos A y B son un par de enantiómeros, y el compuesto C es un diastereómero de ambos. ¿El compuesto C tiene su propio enantiómero? El compuesto D es la imagen especular del compuesto C, y los dos no son superponibles. Por lo tanto, C y D son un par de enantiómeros. El compuesto D es también un diastereómero de los compuestos A y B.

Esto también puede parecer muy confuso al principio, pero hay algunos atajos simples para analizar estereoisómeros:

Stereoisomer shortcuts

If all of the chiral centers are of opposite R/S configuration between two stereoisomers, they are enantiomers.

If at least one, but not all of the chiral centers are opposite between two stereoisomers, they are diastereomers.

(Note: these shortcuts to not take into account the possibility of additional stereoisomers due to alkene groups: we will come to that later)

Here's another way of looking at the four stereoisomers, where one chiral center is associated with red and the other blue. Pairs of enantiomers are stacked together.

We know, using the shortcut above, that the enantiomer of RR must be SS - both chiral centers are different. We also know that RS and SR are diastereomers of RR, because in each case one - but not both - chiral centers are different.

Diastereomers vs. Enantiomers in Wine Chemistry

Tartaric acid, C₄H₆O_6, is an organic compound that can be found in grape, bananas, and in wine. The structures of tartaric acid itself is really interesting. Naturally, it is in the form of (R,R) stereocenters. Artificially, it can be in the meso form (R,S), which is achiral. R,R tartaric acid is enantiomer to is mirror image which is S,S tartaric acid and diasteromers to meso-tartaric acid (Figure 5.6.2).

(R,R) and (S,S) tartaric acid have similar physical properties and reactivity. However, meso-tartaric acid have different physical properties and reactivity. For example, melting point of (R,R) & (S,S) tartaric is about 170 degree Celsius, and melting point of meso-tartaric acid is about 145 degree Celsius.

Diastereomers vs. Enantiomers in Sugar Chemistry

D-erythrose is a common four-carbon sugar.

A note on sugar nomenclature: biochemists use a special system to refer to the stereochemistry of sugar molecules, employing names of historical origin in addition to the designators 'D' and 'L'. You will learn about this system if you take a biochemistry class. We will use the D/L designations here to refer to different sugars, but we won't worry about learning the system.

As you can see, D-erythrose is a chiral molecule: C₂ and C₃ are stereocenters, both of which have the R configuration. In addition, you should make a model to convince yourself that it is impossible to find a plane of symmetry through the molecule, regardless of the conformation. Does D-erythrose have an enantiomer? Of course it does – if it is a chiral molecule, it must. The enantiomer of erythrose is its mirror image, and is named L-erythrose (once again, you should use models to convince yourself that these mirror images of erythrose are not superimposable).

Notice that both chiral centers in L-erythrose both have the S configuration.

Note

In a pair of enantiomers, all of the chiral centers are of the opposite configuration.

What happens if we draw a stereoisomer of erythrose in which the configuration is S at C₂ and R at C₃? This stereoisomer, which is a sugar called D-threose, is not a mirror image of erythrose. D-threose is a diastereomer of both D-erythrose and L-erythrose.

The definition of diastereomers is simple: if two molecules are stereoisomers (same molecular formula, same connectivity, different arrangement of atoms in space) but are not enantiomers, then they are diastereomers by default. In practical terms, this means that at least one - but not all - of the chiral centers are opposite in a pair of diastereomers. By definition, two molecules that are diastereomers are not mirror images of each other.

L-threose, the enantiomer of D-threose, has the R configuration at C₂ and the S configuration at C₃. L-threose is a diastereomer of both erythrose enantiomers.

Erythronolide B, a precursor to the 'macrocyclic' antibiotic erythromycin, has 10 stereocenters. It’s enantiomer is that molecule in which all 10 stereocenters are inverted.

In total, there are 2¹⁰ = 1024 stereoisomers in the erythronolide B family: 1022 of these are diastereomers of the structure above, one is the enantiomer of the structure above, and the last is the structure above.

We know that enantiomers have identical physical properties and equal but opposite degrees of specific rotation. Diastereomers, in theory at least, have different physical properties – we stipulate ‘in theory’ because sometimes the physical properties of two or more diastereomers are so similar that it is very difficult to separate them. In addition, the specific rotations of diastereomers are unrelated – they could be the same sign or opposite signs, and similar in magnitude or very dissimilar.

Exercises

1. Draw the structures of L-galactose (the enantiomer of D-galactose) and two more diastereomers of D-glucose (one should be an epimer).

2. Determine the stereochemistry of the following molecule:

Answer

1.

2.

Contributors and Attributions

• Organic Chemistry With a Biological Emphasis by Tim Soderberg (University of Minnesota, Morris)

• Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)