Early in this chapter we said that most of the molecules in Nature are chiral, and that Nature usually produces these molecules as single enantiomers. We’ve talked about the amino acids, the sugars, ephedrine, pseudoephedrine, and tartaric acid—all compounds that can be isolated from natural sources as single enantiomers. On the other hand, in the laboratory, if we make chiral compounds from achiral starting materials we are doomed to get racemic mixtures. So how do chemists ever isolate compounds as single enantiomers, other than by extracting them from natural sources? We’ll consider this question in much more detail in Chapter 41, but here we will look at the simplest way: using Nature’s enantiomerically pure compounds to help us separate the components of a racemic mixture into its two enantiomers. This process is called resolution. Imagine the reaction between a chiral, but racemic, alcohol and a chiral, but racemic, carboxylic acid, to give an ester in an ordinary acid-catalysed esterification .

The product contains two chiral centres, so we expect to get two diastereoisomers, each a racemic mixture of two enantiomers. Diastereoisomers have different physical properties, so they should be easy to separate, for example by chromatography.

We could then reverse the esterification step and hydrolyse either of these diastereoisomers, to regenerate racemic alcohol and racemic acid.

If we repeat this reaction, this time using an enantiomerically pure sample of the acid, available from (R)-mandelic acid, the almond extract you met on p. 310, we will again get two diastereoisomeric products, but this time each one will be enantiomerically pure. Note that the stereochemistry shown here is absolute stereochemistry.

If we now hydrolyse each diastereoisomer separately, we have done something rather remark able: we have managed to separate two enantiomers of the starting alcohol.

A separation of two enantiomers is called a resolution. Resolutions can be carried out only if we make use of a component that is already enantiomerically pure: it is very useful that Nature provides us with such compounds; resolutions nearly always make use of compounds derived from nature.

Natural chirality , Why Nature uses only one enantiomer of most important biochemicals is an easier question to answer than how this asymmetry came about in the fi rst place, or why L-amino acids and D-sugars were the favoured enantiomers, since, for example, proteins made out of racemic samples of amino acids would be complicated by the possibility of enormous numbers of diastereomers. Some have suggested that life arose on the surface of single chiral quartz crystals, which provided the asymmetric environment needed to make life’s molecules enantiomerically pure. Or perhaps the asymmetry present in the spin of electrons released as gamma rays acted as a source of molecular asymmetry. Given that enantio-metrically pure living systems should be simpler than racemic ones, maybe it was just chance that the L-amino acids and the D-sugars won out.

Now for a real example. Chemists studying the role of amino acids in brain function needed to obtain each of the two enantiomers of the amino acid in the margin. They made a racemic sample using the Strecker synthesis of amino acids that you met in Chapter 11. The racemic amino acid was treated with acetic anhydride to make the mixed anhydride and then with the sodium salt of naturally derived, enantiomerically pure alcohol menthol to give two diastereo isomers of the ester. One of the diastereoisomers turned out to be more crystalline (that is, to have a higher melt ing point) than the other and, by allowing the mixture to crystallize, the chemists were able to isolate a pure sample of this diastereoisomer. Evaporating the diastereoisomer left in solution (the ‘mother liquors’) gave them the less crystalline diastereoisomer

Next the esters were hydrolysed by boiling them in aqueous KOH. The acids obtained were enantiomers, as shown by their (nearly) opposite optical rotations and similar melting points. Finally, a more vigorous hydrolysis of the amides (boiling for 40 hours with 20% NaOH) gave them the amino acids they required for their biological studies. 

مواضيع ذات صلة

Significance of the SN2 rate equation

Mechanisms for nucleophilic substitution

Resolutions using diastereoisomeric salts

Chiral compounds with no stereogenic centres

Diastereoisomers can arise when structures have more than one stereogenic centre

Absolute and relative stereochemistry

Diastereoisomers can be chiral or achiral

Dia stereoisomers are stereoisomers that are not enantiomers

The rotation of plane-polarized light is known as optical activity

R and S can be used to describe the configuration of a chiral centre

Many chiral molecules are present in nature as single enantiomers

Stereogenic centres