Chiral Chemistry

Over 50% of approved new chemical entities (NCEs) in the pharmaceutical industry contain at least one stereogenic center. Chiral compounds have a fixed spatial arrangement of their atoms creating enantiomeric pairs which often exhibit contrasting biological activities. At Symeres, we are committed to being at the technological forefront of chiral chemistry and we employ a comprehensive array of state-of-the-art-chiral technologiesto obtain the desired compound in high enantiomeric purity.

Our extensive toolbox of techniques and methodologies include:

Classical Resolutions: Leveraging classical resolution techniques, we can effectively separate enantiomers based on their differential interactions with chiral resolving agents and thereby isolating each enantiomer in its chiral pure form.

Enzymatic Resolutions: Harnessing the power of biocatalysis, we utilize enzymes to catalyze the conversion of racemic mixtures into optically pure enantiomers. This green and sustainable approach enables the achievement of exquisite levels of enantiomeric purity.

Chiral Chromatography: Our state-of-the-art chiral chromatography systems enable precise separation of enantiomers by chiral stationary phases, ensuring the isolation of individual enantiomers.

Asymmetric Synthesis: We are pioneers in asymmetric synthesis, employing cutting-edge methodologies such as organocatalysis, transition-metal catalysis, and other innovative strategies to directly synthesize single enantiomers. 

In pre-clinical development, time constraints often lead to relying on chiral chromatography and classical resolution methods as the primary tools for isolating a single enantiomer. However, as we advance through the later stages of clinical development, pathways need to be established that yield pure chiral compounds with a theoretical yield of 100%. 

To achieve this goal, various approaches are explored. One avenue involves the development of asymmetric synthesis, employing catalytic techniques such as biocatalysis and traditional chemocatalysis. Alternatively, we can enhance known resolution methods, which typically yield up to 50%, to achieve up to 100% yield. This can be accomplished by introducing racemization conditions, such as mild basic environments or the establishment of (retro)synthetic equilibria. This racemization can take place within the same reaction vessel (dynamic resolution) or in an external, separate process (offline loop). Many unnatural amino acids have been obtained in yields of >80% at Symeres by applying one of these methods.

Two Symeres examples are shown below. 

Classical diastereomeric salt resolution with an offline racemization loop[1].

Attrition-enhanced chiral resolution (also called a ‘Viedma Ripening’) where quantitative yields of the single enantiomer can be obtained from the racemic mixture without the use of any other chiral reagent. Prerequisites are conglomerate crystallization behavior and racemizing conditions[2].

In case you’re in need of a chiral compound in your drug development project, don’t hesitate to reach out directly to our experts via the form below.

[1] Y. Okumura et al., US2020/11555023 B2

[2] W. L. Noorduin et al., Angew. Chem. Int. Edit. 2008, 34 , 6445-6447, DOI: https://doi.org/10.1002/anie.200801846

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