Over 50% of approved new chemical entities (NCEs) contain at least one stereogenic center. At Symeres, we apply all state-of-the-art-chiral technologies, including classical resolutions, enzymatic resolutions, chiral chromatography, and asymmetric synthesis, to obtain the desired compound in high enantiomeric purity.
Although in pre-clinical development, due to time constraints, chiral chromatography and classical resolution methods are often the methods of choice to obtain the single enantiomer, routes to the pure chiral compound with 100% theoretical yield are most desired in later stages. One can try to develop an asymmetric synthesis using, for example, new catalytic methods (bio- and chemocatalysis) or turn the known resolution method (max 50% yield) into 100% theoretical yield by applying racemization conditions (e.g., by applying mild basic conditions or establishing (retro)synthetic equilibria). The latter can occur in the same vessel (dynamic resolution) or in an external (offline) loop. Many unnatural amino acids have been obtained in yields of >80% at Symeres by applying one of these methods.
Below are shown two examples:
- Classical diastereomeric salt resolution with an offline racemization loop
- 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.
If you are in need for a chiral compound in whatever stage of your drug development don’t hesitate to reach out to Symeres.