How are diastereomers used to separate racemic mixtures into their separate enantiomers?

1 Answer
Jan 19, 2016

A racemic mixture of enantiomers are separated into diastereomers by reaction with a homochiral species.


You have a mixture of #R'# and #S'# ENANTIOMERS that are CHEMICALLY identical in a 50:50 mix. You throw in species from the so-called chiral pool (these are chiral reagents derived from NATURAL sources that already display a particular chirality, say #R#).

Now you have a PAIR of salts: #R'R# and #S'R#. These salts ARE NOT mirror images, and hence are DIASTEREOMERS. While still optically active, these have (in principle) different chemical and physical properties. One diastereomer may have solubility in a particular solvent; the other may not. This is thus a means of separation.

If it sounds tedious, indeed it is. It is the world of fractional crystallization to the #n^(th)# degree, but most drugs (that are chiral) have to go thru these steps. An alternative way is to take the enantiomeric mixture and react with a chiral reagent. One isomer may react preferentially with the added reagent to give a new compound, and this offers the possibility of a chiral resolution.

Some chemists naturally have green fingers, and are good at resolving enantiomers. There must be quite a few of these at the drug companies. I doubt that they get as much money or recognition as the company directors.