What Is The Importance Of Stereochemistry

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Since the foundations of stereochemistry were first considered by Louis Pasteur in 1848 and its importance highlighted when he famously said that the universe is chiral (L'Univers est dissymétrique 1) this sub-discipline of chemistry has evolved into an integral area of research in understanding a drug molecules pharmacological effect. The important role of stereochemistry in API (Active Pharmaceutical Ingredient) drug design is reflected in the international regulations and guidelines which address this topic. The FDA has guidelines in place calling for absolute stereochemistry of a molecule to be known for compounds with chiral centred molecules 3. ICH guidelines Q6A 3.3.1 (d) outlines tests and stereochemical aspects that must be considered …show more content…

Isomers are molecules which have an identical atomic composition but differ in their spatial or bonding arrangements 5. Isomers can be further divided up into constitutional (structural) isomers and stereoisomers (spatial isomers) 3. An example of structural isomers are ethanol and dimethyl ether. Both these chemicals have the molecular formula C2H6O but differ in their chemical structures. Ethanol has the chemical structure CH3¬CH2OH while dimethyl ether has the chemical structure CH3OCH3. These two compounds have completely different physical and chemical properties and are therefore easily identified and separated 6. Another example of structural isomers are catechol, resorcinol and hydroquinone which all have the same molecular formula C6H6O2 but different bonding arrangement of their atoms5. Stereoisomers are of importance in API synthesis because they are not as readily identifiable as structural isomers and therefore require a more in depth analysis of the drug molecule or substance. Stereoisomers can be further subdivided into two different categories; configurational isomers which includes geometric isomers and optical isomers, and conformational …show more content…

The symbol ‘E’ is derived from the German word ‘entgegen’ which means ‘opposite’ 8. If the two groups with the higher priorities are on the same side of the double bond, then it is the (Z)- isomer. The symbol ‘Z’ is derived from the German word ‘zusammen’ which means ‘together’ 8. Tamoxifen and doxepin are some examples of pharmaceutical compounds where the geometry of the atoms or groups around its carbon-carbon double bond impact its pharmacological activity. Tamoxifen is an estrogen antagonist used in the treatment of breast cancer 9. The activities of its isomers are completely opposite to each other. The (Z)- isomer of Tamoxifen acts as an estrogen antagonist (binds to the receptor without activating it), while the (E)- isomer of Tamoxifen acts as an estrogen agonist (can fully bind to its receptor and activate it) 9. The mixture of (E) and (Z) isomers in the Tamoxifen racemate may have reduced efficacy due to the binding of the (Z)- isomer to the receptors and blocking binding sites for the (E)-

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