Enantiomers are two molecules with the same chemical composition, mirror images of each other, which do not overlap. Produced in equal quantities during a chemical reaction, they may exhibit opposite biological properties.
Isolating one of them is therefore essential but also very complex due to their nearly identical physical properties. Scientists propose a new strategy to simultaneously prepare and separate two enantiomers of the same molecule.
A molecule is said to be chiral (from the Greek χείρ (kheír), meaning hand) when it can adopt two forms, called enantiomers, with the same chemical composition, mirror images of each other and non-superposable. Much like our two hands. Two enantiomers share the same physical properties except for the deviation of polarized light.
However, in a biological environment, two enantiomers may have different chemical properties: one enantiomer of a drug can have therapeutic virtues while the other is toxic. Having access to each of the enantiomers of a molecule thus becomes crucial but also regulatory, especially for clinical trials of new drugs.
During their synthesis, the two enantiomers are most often produced in equal quantity forming a so-called "racemic" mixture. Indeed, selectively synthesizing only one of the two enantiomers proves to be very difficult. Several strategies have therefore been developed to separate the enantiomers from a racemic mixture.
For instance, one of the enantiomers can be selectively reacted using a chiral catalyst: it is transformed while the other remains intact. The use of chiral membranes acting as filters to separate the two enantiomers is another research avenue being explored.
© Cyril Bressy & Damien Hérault
Scientists from the Institute of Molecular Sciences of Marseille (CNRS/ Aix-Marseille University / Centrale Méditerranée) propose an original strategy to simultaneously prepare and physically separate two enantiomers of a molecule from a racemic substrate.
This approach combines two mirror-image chiral catalysts working in parallel and a separation through a non-chiral membrane with selective permeability. Successfully tested on the Jacobsen HKR model reaction, which allows obtaining chiral 1,2-diols* from racemic epoxides**, it could extend to other reactions leading to key chiral building blocks in organic or pharmaceutical synthesis. Findings can be seen in the
Journal of the American Chemical Society.
Notes:
* A diol is an organic compound bearing two hydroxyl groups (-OH).
** A functional group where two carbon atoms are connected by an oxygen atom.
Writer: CCdM
Reference:
Jingke Hou, Sabine Chevallier-Michaud, Marion Jean, Luc Favre, Damien Hérault & Cyril Bressy.
Physical Separation of Enantiomeric Products by Compartmentalized Parallel Kinetic Resolution
J. Am. Chem. Soc. 2023, 145, 27236-27241.
https://pubs.acs.org/doi/10.1021/jacs.3c12120