Stereochemistry

Thalidomide example

Stereochemistry has important applications in the field of medicine, particularly pharmaceuticals. An often cited example of the importance of stereochemistry relates to the thalidomide disaster. Thalidomide is a pharmaceutical drug, first prepared in 1957 in Germany, prescribed for treating morning sickness in pregnant women. The drug was discovered to be teratogenic, causing serious genetic damage to early embryonic growth and development, leading to limb deformation in babies. Several proposed mechanisms of teratogenicity involve different biological functions for the (R)- and (S)-thalidomide enantiomers. In the human body, however, thalidomide undergoes racemization: even if only one of the two enantiomers is administered as a drug, the other enantiomer is produced as a result of metabolism. Accordingly, it is incorrect to state that one stereoisomer is safe while the other is teratogenic. Thalidomide is currently used for the treatment of other diseases, notably cancer and leprosy. Strict regulations and controls have been implemented to avoid its use by pregnant women and prevent developmental deformities. This disaster was a driving force behind requiring strict testing of drugs before making them available to the public.

In yet another example, the drug ibuprofen can exist as (R)- and (S)-isomers. Only the (S)-ibuprofen is active in reducing inflammation and pain.

Diastereomers

Isomers are of two types: diastereomers (also called diastereoisomers) and enantiomers. Enantiomers are non-superimposable mirror images. Diastereomers are all other types of isomers.

Epimers

Epimers are a subcategory of diastereomers that differ in absolute configuration configurations at only one corresponding stereocenter. They are commonly found in sugar chemistry, where two sugars can differ by the configuration of a single carbon atom. D-glucose and D-galactose are epimers, differing only at the C-4 position in their structure. (see sugar numbering)

Cis-Trans isomers

Cis-Trans isomers are often associated alkene double bonds.

The more general E/Z nomenclature refers to the concept of cis/trans isomerism, and is especially useful for more complex compounds.

Atropisomers

Atropisomerism are another kind of diasteromer. They exist because of the inability to rotate about a bond, such as due to steric hindrance between functional groups on two sp²-hybridized carbon atoms. Usually atropisomers are chiral, and as such they are a form of axial chirality. Atropisomerism can be described as conformational isomerism

History

In 1815, Jean-Baptiste Biot's observation of optical activity marked the beginning of organic stereochemistry history. He observed that organic molecules were able to rotate the plane of polarized light in a solution or in the gaseous phase. Despite Biot's discoveries, Louis Pasteur is commonly described as the first stereochemist, having observed in 1842 that salts of tartaric acid collected from wine production vessels could rotate the plane of polarized light, but that salts from other sources did not. This was the only physical property that differed between the two types of tartrate salts, which is due to optical isomerism. In 1874, Jacobus Henricus van 't Hoff and Joseph Le Bel explained optical activity in terms of the tetrahedral arrangement of the atoms bound to carbon. Kekulé explored tetrahedral models earlier, in 1862, but never published his work; Emanuele Paternò probably knew of these but was the first to draw and discuss three dimensional structures, such as of 1,2-dibromoethane in the Giornale di Scienze Naturali ed Economiche in 1869. The term "chiral" was introduced by Lord Kelvin in 1904. Arthur Robertson Cushny, a Scottish Pharmacologist, first provided a clear example in 1908 of a bioactivity difference between enantiomers of a chiral molecule viz. (−)-Adrenaline is two times more potent than the (±)- form as a vasoconstrictor and in 1926 laid the foundation for chiral pharmacology/stereo-pharmacology (biological relations of optically isomeric substances). Later in 1966, the Cahn–Ingold–Prelog nomenclature or Sequence rule was devised to assign absolute configuration to stereogenic/chiral center (R- and S- notation) and extended to be applied across olefinic bonds (E- and Z- notation).