Chiral resolution

The use of chiral resolution to obtain enantiomerically pure compounds has the disadvantage of necessarily discarding at least half of the starting racemic mixture. Asymmetric synthesis of one of the enantiomers is one means of avoiding this waste.

Crystallization of diastereomeric salts

The most common method for chiral resolution involves conversion of the racemic mixture to a pair of diastereomeric derivatives by reacting them with chiral derivatizing agents, also known as chiral resolving agents. The derivatives which are then separated by conventional crystallization, and converted back to the enantiomers by removal of the resolving agent. The process can be laborious and depends on the divergent solubilities of the diastereomers, which is difficult to predict. Often the less soluble diastereomer is targeted and the other is discarded or racemized for reuse. It is common to test several resolving agents. Typical derivatization involves salt formation between an amine and a carboxylic acid. Simple deprotonation then yields back the pure enantiomer. Examples of chiral derivatizing agents are tartaric acid and the amine brucine. The method was introduced (again) by Louis Pasteur in 1853 by resolving racemic tartaric acid with optically active (+)-cinchotoxine.

In some cases, only 0.5 equivalents of a chiral acid or base are reqiured.

Common resolving agents

The chiral pool consists of widely available resolving agents. They are always natural products or derived from them.

• Tartaric acid, an acid that forms diastereomeric salts with chiral amines
• Antimony potassium tartrate, an anion, that forms diastereomeric salts with chiral cations.
• Mandelic acid, an acid that forms diastereomeric salts with chiral amines.
• Camphorsulfonic acid, an acid that forms diastereomeric salts with chiral amines. Also 3-bromocamphor-8-sulfonic acid
• 1-Phenylethylamine, a base that forms diastereomeric salts with chiral acids. Many related chiral amines have been demonstrated.