ABSTRACT
Implementation of stereochemistry in pharmaceuticals dates back to the late 1850’s, when Pasteur reported that most natural organic products, the vital products of life, are asymmetric and possess such asymmetry that they are not superimposable on their images. In 1874, Van’t Hoff and La Bel 436independently reported the relationship between three-dimensional molecular structure and optical activity and the concept of chiral carbon atom. Subsequently, the physiological and toxicological significance of chiral compounds was chiral molecules was explored. Ariens, in the late 1980’s raised the question “why we in some cases have to give doses to the patient where half of the content has no effect or the opposite effect?” After this revival of stereochemistry, the regulatory authorities defined more strict requirements on drug discovery and chiral compounds. Besides the ethical reasons, the therapeutic benefit including safety and, in several instances, extensions of the life cycle of drugs have been essential for developing single enantiomers (Shafaati, 2007). Chiral drugs are made up of molecules with the same chemical structure, but different three-dimensional arrangements in the space. The pharmacological and toxicological effects of the chiral drugs are considered instrumental in drug discovery because of the different activities shown by different enantiomers. Almost all of the biological macromolecules, such as DNA, RNA, protein, polynucleotides, and even the amino acids, the basic structural units of life, are chiral. Most of the natural drugs are chiral, but in nature only the biologically active enantiomer is synthesized. For example, Papaver somniferum only synthesizes (–)-(5R,6S,9R,13S,14R)-morphine which is the active enantiomer used as powerful analgesic. Currently, 56% of the marketed drugs are chiral products and 8.8% of them are marketed as racemic mixtures consisting of an equimolar quantity of two enantiomers.
