*Image courtesy of
Wikimedia Commons
Indeed, the study of enantiomers – chirality – comes from
the Greek word, “Χειρ = Cheir = Hand”!
Enantiomers have identical chemical and physical properties
except for their ability to rotate plane-polarized light by equal amounts but
in opposite directions.
However, in biological systems, they can have very different
behavior. Some of the most interesting –
and important – differences are in drug metabolism.
For the better part of a century, the consideration of
enantiomers in drug metabolism was limited to academic study and/or to natural
products, owing in no small part to the limits of separations chemistry.
However, for many reasons (including improvements in
analytical chemistry), chirality has been earning ever-greater importance in
drug discovery and development, such that many new drugs reaching the market in
the first decades of the 21st century are single enantiomers, rather than the
racemic mixtures (or achiral drugs) that dominated the latter half of the 20th
century.
Indeed, in the recent report, “The Year in New Drugs” (C&E News, February 1, 2016, pp.
12-17), it can be seen that more than half of the newly-approved small-molecule
drugs in 2015 had specific stereochemistry (and often with more than one chiral
center).
Examples of enantio-selective biotransformations include:
- Prochiral to Chiral
- Chiral to Chiral
- Chiral to Achiral
- Chiral to Diastereoisomer
- Chiral Inversion
These metabolism pathways can have significant effects on
pharmacology and drug safety. While the movement towards single enantiomers as
drug candidates, noted above, mitigates safety problems that might be associated with racemic mixtures, they do
not necessarily alleviate the need to consider and study achiral-to-chiral, chiral-to-chiral,
and/or chiral-to-diastereomer transformations.
