In past blog entries I have shown that enantiomers are optical isomers which are nonsuperimposable mirror-image structures. A mixture of equal portions (50/50) of the (+) and (-) enantiomers is called a racemic mixture. The chirality of a compound is very important when interacting with a chiral medium as the human body, the biological effect directly depending on the stereochemistry of the compound and the receptor in the body. Thus, a single-enantiomer drug can be pharmacologically interesting whereas its mirror image can be inactive or display a different desirable or non-desirable activity.
The thalidomide disaster is one of the darkest episodes in pharmaceutical research history. Chirality of molecules played a crucial role in this story and underscored its importance in organic synthesis of pharmaceuticals.
In 1957, a pharmaceutical company in West Germany introduced a new drug to the market. It was called thalidomide. The drug was sold in several countries as a sedative and sleeping drug for pregnant women. The thalidomide is a chiral molecule. However, the drug was made and marketed as a racemic mixture of the (+)-(R)-thalidomide and (-)-(S)-thalidomide.
Tragically, thalidomide was found to have serious side-effects; thousands of babies were born with missing or abnormal arms, hands, legs, or feet. It was banned by many countries in 1961. Nowadays scientists know that it is the (-)-(S)-thalidomide that caused the severe side-effects. (+)-(R)-thalidomide is a sedative, but (-)-(S)-thalidomide is a teratogen (i.e., a drug that can harm a foetus in the womb).
Thus, (-)-(S)-thalidomide is the unwanted enantiomer. You might think that pharma companies can simply purify the racemic mixture and give patients only the (+)-(R)-thalidomide. Unfortunately, the answer is not that simple in this specific case. Human liver contains an enzyme that can convert (+)-(R)-thalidomide to (-)-(S)-thalidomide. Therefore, even administration of enantiomerically pure (+)-(R)-thalidomide results in a racemic mixture. It is said that in the human body thalidomide undergoes racemization.
This disaster was a driving force behind requiring strict testing of drugs before making them available to the public. Now there is rigorous testing before launching new drugs into the market. The ban of thalidomide was lifted in 1985 by the World Health Organization. Today, thalidomide is used experimentally in all continents to treat various cancers and inflammatory diseases.
Despite of the fact of the racemization of thalidomide in the body, this example illustrates the importance of obtaining just only one single enantiomer. In fact, in the pharmaceutical field, chirality of molecules is placed in an extremely relevant position. The administration of enantiopure drugs (i.e. a pharmaceutical that is available in one specific enantiomeric form) brings benefits in terms of improved efficacy, and reduced toxicity. These advantages forced pharmaceutical companies and health authorities to place stereochemically pure substances in a privileged position.
The large demand of enantiopure products has broken out the progress of chemical synthesis. Nowadays, the number of synthetic methods available for the preparation of chiral molecules has permitted to efficiently gain access to a myriad of enantiomerically pure compounds.